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Chicago Conference Highlights & Insights for Rheumatology Specialists American College of Rheumatology/ Association of Rheumatology Health Professionals 2018 Annual Meeting October 19–24, 2018 Chicago, IL ACR

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Page 1: ACR - jmcp.org › pb-assets › Outserts › 18100_ACR...American College of Rheumatology/ Association of Rheumatology Health Professionals 2018 Annual Meeting ACR October 19–24,

Chicago

Conference Highl ights & Ins ights for Rheumatology Specia l is ts

American College of Rheumatology/ Association of Rheumatology Health Professionals2018 Annual MeetingOctober 19–24, 2018Chicago, IL

ACR

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ACR 2018 Annual Meeting

PUBLISHERGene Conselyea

WRITERKeightley Amen, BA, ELS

EDITORKerri Fitzgerald

ART DIRECTORAri Mihos

630 Madison Avenue2nd FloorManalapan, NJ 07726

©2018 American Medical Communications, Inc, Manalapan, NJ 07726

GRAPHIC DESIGNERLisa Adamitis

PROJECT MANAGERStephanie Maloney

ACCOUNT MANAGERS Ron Gordon Gene Conselyea

American College of Rheumatology/ Association of Rheumatology Health Professionals 2018 Annual MeetingOctober 19–24, 2018 • Chicago, ILACR

Table of Contents1 Making Medication Adherence “the Fifth

Vital Sign”

1 De-Hyping Artificial Intelligence and Machine Learning in Health Care

2 Questions to Consider When Collecting Patient-Generated Data

3 American College of Rheumatology Prepares Guideline on Reproductive Health in Rheumatic Disease

6 IQ-Lupus Program Decreases Hospitalizations Among High-Risk Patients

6 Genetic Risk Score May Identify Ankylosing Spondylitis Earlier

7 A Divorce Between Psoriatic Arthritis and Rheumatoid Arthritis

15 Treatment of Patients with AS, PsA, and PsO

16 Women Abused During Childhood Have Significantly Higher Risk of Lupus

17 Study Finds That Intensity of Walking Affects Risk of Knee Replacement

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Making Medication Adherence “the Fifth Vital Sign”

During an afternoon of specialized pre-meeting ses-sions at the annual meeting, speakers addressed various aspects of health technology. One presenter,

Bernard Vrijens, PhD, of AARDEX Group, stressed to at-tendees that “Medication Adherence Is a Key Element to Integrate in e-Health.”

The speaker began by quoting former U.S. Surgeon General C. Everett Koop: “Drugs don’t work in patients who don’t take them.” Adherence is key to therapeutic success, Dr. Vrijens said.

He outlined three steps along the adherence journey: Pa-tients must initiate therapy, implement the dosing regimen, and then persist. However, he cited studies that have found 20% to 30% of patients do not initiate prescriptions, 15% do not implement doses as prescribed daily (due to missing a dose, taking an extra dose, or missing a dose), and 40% discontinue treatment by the twelfth month, demonstrating problems all along the adherence journey.

Variable adherence creates drug-specific issues of ef-ficacy, safety, and drug resistance, Dr. Vrijens continued. Suboptimal adherence leads to treatment failure, disease progression, and adverse events, then more complex treat-ments to address the ensuing issues. It is a complex and expensive loop, he stated, so healthcare practitioners must abandon the “struthian approach” of burying our heads in the sand. Instead, they must better capture true adherence rates and understand the consequences.

“Medication adherence is a vital sign to measure and manage,” he concluded.

Next, Dr. Vrijens reviewed the weaknesses of the avail-able methods to assess adherence in ambulatory patients, including direct methods (measuring pharmacokinetics and pharmacodynamics), self-report, pill counts, and prescrip-tion and refill databases (currently the gold standard).

He encouraged the audience to consider the utility of electronic monitoring and institute knowledge at all points of care. He said a systems approach is the only way to successfully combat the problem. Such an approach would involve adjusting health care and prescribing poli-cies; involving the community and other institutions; and educating healthcare practitioners, prescribers, patients, their families, and their friends. One study cited found that awareness of adherence patterns is the best way to change patient behavior, so he proposed using patients’ social net-works to make patients aware and more adherent.

Finally, Dr. Vrijens acknowledged that physicians and other healthcare practitioners have heavy workloads and

limited resources, so algorithms and systems can help al-leviate the adherence problem. However, he stressed that technological solutions do not replace physicians; rather, they redefine their role and require a multidisciplinary ap-proach.

“Healthcare systems must evolve to meet the challenge of achieving satisfactory adherence to therapeutic drug regimens,” he said, guiding attendees to consider patient-tailored approaches, measurement-guided interventions, and e-health. ●

De-Hyping Artificial Intelligence and Machine Learning in Health Care

Prior to the annual meeting, the ACR Clinical Research Conference focused on technology advances that are changing the landscape of medicine and rheumatolo-

gy. Beyond electronic health records, there is a broad range of digital and mobile technologies.

One of the sessions addressed artificial intelligence (AI). Geoffrey Tison, MD, MPH, a cardiologist at the University of California San Francisco, framed the discussion by acknowledging how physicians and other healthcare providers are overworked. They are being asked to do more with less time and fewer resources, he said. So, can AI help? “The topic is surrounded by a fair amount of hype,” he said. “And I’d like to demystify that somewhat today.”

Simply put, he said, machine learning has taken the best of computer science and statistics and married the two. To perform machine learning, one defines a task, takes a large amount of data, puts it into a model, and then allows the machine to provide output.

For example, in his research applying AI to identify atrial fibrillation (AF), Dr. Tison and his team entered many

“Medication adherence is a vital sign to measure and manage.”

—Bernard Vrijens, PhD

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ACR 2018 Annual Meeting

2

electrocardiogram results (EKGs)—some that showed AF and some that did not—and labeled them as such, so that the machine could learn to recognize future EKGs as positive or negative for AF.

Although Dr. Tison described his work using applications of machine learning in cardiology, he believes the model is applicable to rheumatology and many other specialties within medicine. He cited examples of image recognition and machine learning to identify skin cancer and detect diabetic retinopathy.

Despite the possibilities, Dr. Tison cited limitations as well. Such models are very “data hungry,” needing thou-sands or tens of thousands of data points. Data must be labeled by humans first, which is cost prohibitive and time consuming. In addition, there is a potential lack of inter-pretability.

He concluded, “Humans no longer have a monopoly on complex problem solving, but in the age of machine learn-ing, epidemiology remains as important as ever.” ●

Questions to Consider When Collecting Patient-Generated Data

Prior to the start of the annual meeting, an afternoon of presentations focused on “Applications of Mobile Health Technologies.”

Eric M. Ruderman, MD, of the Feinberg School of Medi-cine at Northwestern University, encouraged participants to consider many essential questions during his talk, “Efficient Collection of Patient-Generated Data.”

The overarching question, he said, is to decide which data to collect and for what goal, such as research, clini-cal care, or target a particular issue. Focusing on patient-generated data in the clinical settings, Dr. Ruderman said practitioners must make sure that data patient-reported outcome measures are:

• feasible (able to be collected and used effectively)

• meaningful

• minimal (presenting a low collection burden)

Furthermore, Dr. Ruderman said, practitioners should consider how much data they want to collect, taking into account the complexity of tools, how precise the tools are and whether precision will actually be used in clinical care, and patients’ willingness to complete instruments, includ-ing “questionnaire fatigue.” Ultimately, for data to contribute to clinical care, the information must be collected in real time and must be concise, meaningful, and actionable, “oth-erwise you’re spinning your wheels,” he said.

Once these larger questions are addressed, many impor-tant considerations remain. For example, Dr. Ruderman spe-cifically reviewed three times when patients can provide data.

When collecting data during patient visits, practitioners must weigh when to collect data, whether to collect it from every patient at every visit, how data collection with affect workflow, and who will be responsible for data collection and entry. “How much time will data collection realistically take?” Dr. Ruderman asked, and when will it be done—dur-ing the appointment when the patient and physician are face to face, or on a tablet when the patient is in a waiting room?

Alternatively, when practices ask patients to provide such information before a visit, logistical questions arise, such as whether to use paper, web-based systems, or apps. One of the more difficult aspects of pre-visit data collection is deciding who ensures that it occurs, sends reminders to patients, and delivers the data to the physician.

Some practices are starting to collect between-visit data, using apps or web-based solutions. Again, Dr. Ruderman asked participants to consider who will be responsible for entering the data, tracking changes longitudinally, and mak-ing sure the data actually adds to the next visit.

Finally, practitioners must think about how to integrate patient-generated data with objective data such as joint counts, physical exams, and laboratory results. Ideally, he said, patient-generated data, objective data, visit notes, and changes over time should all be on the same system.

Although there are many questions to consider and chal-lenges to address—including patient acceptance, patient

“Humans no longer have a monopoly on complex problem solving, but in the age of machine learning, epidemiology remains as important as ever.”

—Geoffrey Tison, MD, MPH

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capabilities, clinical capacity, and infrastructure—Dr. Ruder-man said patient-generated data has many potential benefits, including better outcomes, patient engagement, and improved patient understanding of the importance of adherence.

The next steps in the efficient collection of patient-gener-ated data will be demonstrating value; integrating tools into the electronic health record; and crossing practice domains among care, research, and registries. ●

American College of Rheumatology Prepares Guideline on Reproductive Health in Rheumatic Disease

At its annual meeting, the American College of Rheumatology (ACR) presented a draft of a clini-cal practice guideline to help rheumatologists and

obstetricians/gynecologists manage the reproductive health of patients with rheumatic disease.

According to ACR, the guideline, known as the Repro-ductive Health in Rheumatic Diseases Guideline, is the first evidence-based clinical practice guideline related to the management of all reproductive health issues for patients across the spectrum of rheumatic diseases.

Lisa R. Sammaritano, MD, of Hospital for Special Sur-gery–Weill Cornell Medicine in New York, N.Y., and one of the experts involved in the guideline’s development, said that managing pregnancy, especially in women with condi-tions such as lupus or antiphospholipid antibody syndrome, can be challenging.

“Our patients have particular needs and challenges during pregnancy, and the obstetrician/gynecologist may not always be aware of these,” said Dr. Sammaritano. “In addition, rheumatologists may not be aware of updates in contraception, fertility therapies, and pregnancy manage-ment. With the expansion of new therapies available for rheumatic diseases in recent years, especially in rheuma-toid arthritis, we need to learn more about which of these new treatments are compatible with pregnancy.”

Some of the important considerations in the reproduc-tive health of patients with rheumatic disease are:

• planning pregnancies ahead of time

• conceiving during periods of low disease activity

• conceiving when neither the mother nor father are using teratogenic medications, which could put a fetus at risk

In preparing the guideline, the panel of experts met with a panel of patients who stressed that “they wanted to talk with their rheumatologist about family planning, early and often,” according to Dr. Sammaritano. In fact, patients often seek guidance from their rheumatologists about safe contraception, fertility issues, and safe medication use dur-ing pregnancy and breastfeeding. This guideline will help rheumatologists when their patients ask these important questions about family planning.

To develop the guideline, a panel of rheumatologists, obstetricians/gynecologists, reproductive medicine special-ists, epidemiologists, and patients with rheumatic diseases conducted a systematic review of current, evidence-based literature on all aspects of reproductive health in rheumatic disease. They applied standard GRADE (Grading of Recom-mendations Assessment, Development and Evaluation) methodology to assess the quality of the evidence.

ACR plans three papers on the following topics once the guideline is complete:

1. Reproductive health in general, including contracep-tion, assisted reproductive technology, preservation of fertility for women using cytotoxic medications, and menopause, including estrogen replacement therapy

2. Pregnancy counseling and management.

3. Medication management for men and women ●

“Our patients have particular needs and challenges during pregnancy, and the obstetrician/gynecologist may not always be aware of these.”

—Lisa R. Sammaritano, MD

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IQ-Lupus Program Decreases Hospitalizations Among High-Risk Patients

Systemic lupus erythematosus (SLE), or lupus, is a chronic disease that causes systemic inflammation and affects multiple organs, including kidneys, lung,

heart, and brain, as well as the skin and joints. The condi-tion is far more common in women than in men, and it is more prevalent among African-Americans and Latinos than non-Hispanic whites. Furthermore, the disease is often diag-nosed late or misdiagnosed, and it requires careful manage-ment during pregnancy.

Research presented at the annual meeting shows that patients with high-risk SLE may have a decreased risk of hospitalization and shorter length of stay when they have improved access to rheumatologic care.

Previous research from a team at the University of Rochester Medical Center in New York found that a small group of high-risk, high-cost patients account for most hospitalizations, the majority of length of stay, and most overall cost. Specifically, high-risk, high-cost patients spent three times as many days in the hospital, and such patients often were young women from lower socioeco-nomic backgrounds.

Allen P. Anandarajah, MBBS, the study’s presenting author, said, “These patients often were unable, or unwill-ing, to come to outpatient clinics. We organized focus group meetings with patients from within the high-risk group and recognized that the lack of easy access was a major impedi-ment to routine clinical care.” Therefore, the researchers decided to evaluate the impact of interventions to improve access to rheumatology care.

The study defined high-risk, high-cost patients with lupus as those who required three or more hospital admis-sions over a three-year period between 2013 and 2016. Most of the patients were African-Americans from poor, urban communities. The medical center launched a pro-gram called IQ-LUPUS (Improve Quality in Low-income, Underserved, Poor, Underprivileged, SLE) to improve quality of care for the target population and to enhance their access to rheumatology care. IQ-LUPUS opened a rheumatology clinic in a local urban neighborhood, and it offers patients direct access to a nurse care coordinator and social worker.

Researchers examined data from fiscal year (FY) 2017 to compare no-show rates for the high-risk, high-cost pa-tients at the outpatient clinic with no-show rates of all other lupus patients, as well as all rheumatology patients system-

wide. They also determined hospitalization rates and length of stay for all medical center admissions among study participants, comparing data from the first 10 months of FY 2017 to the first 10 months of FY 2018.

Fifty-four patients enrolled in IQ-LUPUS. In FY 2017, the no-show rate for high-risk, high-cost patients was 12.1% compared with 5.8% for all patients with lupus and 4.3% for all rheumatology patients. The no-show rate for the high-risk, high-cost patients decreased 1.3% in FY 2018 but increased 0.8% in all patients with lupus and 0.7% in all rheumatology patients. Furthermore, hospital admissions and length of stay decreased in the high-risk, high-cost group—from 52 admissions and 231 days to 36 admissions and 159 days. The number of 30-day admis-sions also decreased from 21 in 2017 to 14 in 2018.

The researchers concluded that improved access to rheumatology care through programs such as IQ-LUPUS can decrease hospitalizations and length of hospital stay for high-risk, vulnerable patients. ●

Genetic Risk Score May Identify Ankylosing Spondylitis Earlier

At the annual meeting, a team of researchers pre-sented a new method to accurately assist in the early diagnosis of ankylosing spondylitis (AS). Their

study found that a genetic risk score can help clinicians identify the condition earlier and at lower cost than current testing methods.

AS is a common cause of chronic back pain and may affect the skin, intestines, and eyes. The disease commonly begins during patients’ teens or 20s, is far more common in men than women, and has a strong genetic risk.

Zhixiu Li, PhD, of Queensland University of Technol-ogy Institute of Health and Biomedical Innovation in Australia, said the typical delay between the onset of AS symptoms and diagnosis is eight to 10 years and that patients often receive inappropriate treatment during the delay. Early diagnosis and intervention have been shown to improve outcomes, but early diagnosis can be challenging.

“In early disease, magnetic resonance imaging (MRI) imaging is the current gold standard for diagnosis, but it is very expensive, and many patients with early changes on an MRI scan don’t go on to get AS,” said Dr. Li. “Thus, we

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think genetic profiling may even be informative, particu-larly in early disease, but also potentially prior to onset of symptoms.”

Genetic risk score (GRS) uses thousands of genetic vari-ants to calculate a person’s susceptibility for a particular disease. Dr. Li’s team of researchers examined two mod-els of GRS to determine whether they could serve as an early diagnostic tool in AS. The first model was based on samples of European descent (n=7,742 patients with AS and n=14,542 controls). The second model was based on samples of East Asian descent (n=6,001 patients with AS and n=4,943 controls).

The researchers compared their models with standard testing for AS and reported results using area under the curve (AUC). In the European GRS model, the AUC was 0.92, with 83% sensitivity and 92% specificity compared with 0.87 with human leukocyte antigen-B27 alone. In the East Asian GRS model, the AUC was 0.95, with 91% sensi-tivity and 95% specificity.

“Our findings show that GRS has high discriminatory capacity and could be of clinical utility in early diagnosis at [a] lower cost than MRI,” said Dr. Li. “In addition, [it] could also be applied to identify individuals with [a] substantial risk of developing AS before major symptoms appear. It could also be applied to patients with arthritic symptoms but without a clear diagnosis.”

The researchers are working to improve their models and examining how GRS performs when combined with other clinical features or test results. ●

A Divorce Between Psoriatic Arthritis and Rheumatoid Arthritis

At a dinner symposium hosted by Novartis at the annual meeting, a panel of experts explained the irreconcilable differences between psoriatic arthri-

tis (PsA) and rheumatoid arthritis (RA). The presentation, titled “PsA: Is It Time to Divorce from RA? Identifying Clinical Signs and Symptoms, and Gaining New Insights into Pathophysiology and Management,” highlighted the many important distinctions between PsA and RA—despite the fact that they can have similar presentation and have historically been treated the same.

Philip J. Mease, MD, of the University of Washington School of Medicine in Seattle, introduced the topic, stress-

ing that PsA and RA are distinct diseases. PsA often goes undiagnosed, he said, but early diagnosis is important to outcomes.

DISTINGUISHING PSA FROM RAGrace C. Wright, MD, PhD, president of the Association of Women in Rheumatology, said, “The divorce actually happened a long time ago, we just have to get with the program.”

PsA is part of the spondyloarthritis group of diseases, and she outlined its specific clinical hallmarks, in compari-son with RA:

• PsA involves the axial skeleton and distal interphalan-geal joints, as opposed to the metacarpophalangeal joints and wrist joints in RA.

• PsA can be mono-, oligo-, or polyarticular, as opposed RA, which is polyarticular.

• PsA joints are often asymmetrical, whereas RA joints are mostly symmetrical.

• PsA leads to enthesitis, but RA does not.

• Dactylitis is a hallmark of PsA, but it is rare in RA.

• Patients with PsA do not have a high titer rheumatol-ogy factor, as opposed to those with RA.

• PsA often leads to nail lesions, as opposed to RA.

• PsA involves psoriasis, which can appear before other signs and symptoms; RA does not.

“When we look at PsA, we are not just looking at joints,” Dr. Wright said, adding that innate and adaptive immune responses contribute to the pathogenesis of both PsA and RA, but RA joints are enriched with a range of inflamma-tory cytokines. In PsA, there is inflammatory activation at multiple sites, and PsA joints are enriched with interleukin-17-producing cells. Therefore, “Even if they look the same at presentation, we have to look at the activation to under-stand and treat.”

If left untreated, PsA can have a significant impact on patients’ functional status and quality of life, she said. Because of some of the disease manifestations, patients often are seen by their primary care physicians and special-ists such as dermatologists long before they are referred to rheumatology.

Continued on page 8

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ACR 2018 Annual Meeting

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PSA’S IMPACT ON PATIENTSDr. Mease focused his presentation on PsA’s effects on patients’ lives. Peripheral arthritis can lead to irreversible deformities, pain, stiffness, and loss of function, he said, and the damage is progressive in most patients.

Enthesitis, he continued, also has a significant impact on patients, who report diffuse aches and pains and often pres-ent with a swollen joint or digit but have endured months or years of pain and tenderness. Importantly, he said, the presence of enthesitis is a biomarker of increased disease severity and poorer functional status. Its true prevalence is underestimated, because it may mimic mechanical stress injury or tendonitis, and quantification by physical exami-nation is difficult due to the location of the sites. Dactylitis is also a marker of disease severity, Dr. Mease said—if it is present, it is associated with greater disease burden.

Spine disease is present in 50% of patients with PsA, he continued, but presentation is variable. Patients with this manifestation have poorer physical function and health-related quality of life (HRQOL) than patients with more peripheral involvement. However, about 20% of patients with evidence of axial involvement may not be symptomatic, he said.

Regarding the skin, even a moderate amount of psoriatic skin involvement is associated with greater disease burden, greater reported pain, fatigue, impairment, discomfort, and self-consciousness. Therefore, it is very important to acknowl-edge the skin with patients and evaluate its involvement. In fact, psoriasis often develops into PsA. Nail disease is also im-portant, for similar reasons, but it is difficult to treat. Like the skin, nail psoriasis is closely associated with PsA development.

ASSESSMENT OF PSADr. Mease discussed PsA assessment tools but stressed that “one size does not fit all.”

For clinical trials, he said researchers should assess every item in the inner circle of the OMERACT (Outcome Measures in Rheumatology): musculoskeletal disease activ-ity (including peripheral joints, enthesitis, dactylitis, and spine symptoms), skin diseases activity, and pain. Global as-sessment, physical function, HRQOL, fatigue, and systemic inflammation.

He said the American College of Rheumatology 20 Criteria tend to be the primary endpoint in PsA studies and has served researchers reasonably well in deciphering between treatment and placebo, but new composite measures are being developed to better elucidate disease severity and treatment effectiveness. They are being used more commonly in trials but not quite ready for use in clinical practice, he added.

Finally, Dr. Mease said, “No patient who comes to see you with this disease will be like another patient with the same disease. Take into account the different disease domains for individualized diagnosis and management,” referring attendees to guidelines created by the Group for Research and Assessment of Psoriasis and Psoriatic Arthri-tis (otherwise known as GRAPPA).

PRACTICAL USE OF IMAGINGClinical examination may not provide an accurate or com-plete picture of PsA, said presenter Catherine J. Bakewell, MD, RhMSUS, of Intermountain Medical Group in Salt Lake City, Utah. She offered many images from her prac-tice to demonstrate how imaging can help with diagnosis, proper prognosis, and better disease management.

The main modalities to visualize disease activity in PsA are radiography, ultrasound, and magnetic resonance imag-ing (MRI). Although radiography is fast, inexpensive, and reproducible, it cannot help researchers or clinicians visualize soft tissue or active inflammation, Dr. Bakewell said. MRI can show peripheral arthritis, enthesitis, dactylitis, and nail effects, and it is effective in detecting early disease. However, it cannot detect axial disease and is expensive. Therefore, she recommends ultrasound, which can detect all of those mani-festations, including joints during movement, at a low cost.

In the future, researchers and clinicians may find them-selves using new imaging modalities—even artificial intel-ligence—to diagnose, assess, manage, and monitor patients with PsA. ●

Continued from page 7 “No patient who comes to see you with this disease will be like another patient with the same disease. Take into account the different disease domains for individualized diagnosis and management.”

—Philip J. Mease, MD

Learn about

REAL-WORLD US PATIENTS1*

WITH EXPERIENCE IN

Please see additional Important Safety Information on adjacent pages.Please see Brief Summary of full Prescribing Information on adjacent pages.

INDICATIONSCOSENTYX® (secukinumab) is indicated for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy.COSENTYX is indicated for the treatment of adult patients with active psoriatic arthritis.COSENTYX is indicated for the treatment of adult patients with active ankylosing spondylitis.

IMPORTANT SAFETY INFORMATIONCONTRAINDICATIONSCOSENTYX is contraindicated in patients with a previous serious hypersensitivity reaction to secukinumab or to any of the excipients.

Actual patients who have taken COSENTYX® and have been compensated for their time. Individual results may vary.

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Learn about

REAL-WORLD US PATIENTS1*

WITH EXPERIENCE IN

Please see additional Important Safety Information on adjacent pages.Please see Brief Summary of full Prescribing Information on adjacent pages.

INDICATIONSCOSENTYX® (secukinumab) is indicated for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy.COSENTYX is indicated for the treatment of adult patients with active psoriatic arthritis.COSENTYX is indicated for the treatment of adult patients with active ankylosing spondylitis.

IMPORTANT SAFETY INFORMATIONCONTRAINDICATIONSCOSENTYX is contraindicated in patients with a previous serious hypersensitivity reaction to secukinumab or to any of the excipients.

Actual patients who have taken COSENTYX® and have been compensated for their time. Individual results may vary.

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There are a variety of cell types that can produce IL-17A3

IL-17A is an important mediator in the inflammatory process2

Clinical significance of the COSENTYX mechanism of action is unknown. Images not drawn to scale. The above graphic has been simplified. The immune pathophysiology of psoriatic disease involves complex molecular mechanism feedback loops not shown in this graphic.4,5

The understanding of the pathophysiology of plaque psoriasis and psoriatic arthritis continues to evolve.This represents a current theory of the role of IL-17A in the disease.

Please see additional Important Safety Information on adjacent pages.Please see Brief Summary of full Prescribing Information on adjacent pages.

IMPORTANT SAFETY INFORMATION (cont’d)WARNINGS AND PRECAUTIONSInfectionsCOSENTYX may increase the risk of infections. In clinical trials, a higher rate of infections was observed in subjects treated with COSENTYX compared to placebo-treated subjects. In placebo-controlled clinical trials in patients with moderate to severe plaque psoriasis, higher rates of common infections such as nasopharyngitis (11.4% versus 8.6%), upper respiratory tract infection (2.5% versus 0.7%), and mucocutaneous infections with candida (1.2% versus 0.3%) were observed with COSENTYX compared with placebo. A similar increase in risk of infection was seen in placebo-controlled trials in patients with psoriatic arthritis and ankylosing spondylitis. The incidence of some types of infections appeared to be dose-dependent in clinical studies.Exercise caution when considering the use of COSENTYX in patients with a chronic infection or a history of recurrent infection. Instruct patients to seek medical advice if signs or symptoms suggestive of an infection occur. If a patient develops a serious infection, the patient should be closely monitored and COSENTYX should be discontinued until the infection resolves.

IL-17A is a naturally occurring cytokine involved in normal inflammatory and immune response. Selectively targeting IL-17A with COSENTYX® (secukinumab) inhibits release of pro-inflammatory

cytokines and chemokines—which are implicated in the development of certain types of psoriatic disease.2

IL-17A

TH17 cells

IL-23

Activated dendritic cells

TNFα Mast cells

NeutrophilsOther T cells

Innate lymphoid cells

Go deeper into the body of evidence for COSENTYXvisit www.cosentyxHCP.com

Active comparator data in moderate to severe plaque PsO vs two different comparators

Efficacy and safety data in robust clinical trials

11+ years of clinical trial experience worldwide6

12,600+ unique prescribers to date in the US1

COSENTYX clinical data backed by real-world experience

PsO, psoriasis.

IMPORTANT SAFETY INFORMATION (cont’d)WARNINGS AND PRECAUTIONS (cont’d)Pre-treatment Evaluation for Tuberculosis Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with COSENTYX. Do not administer COSENTYX to patients with active TB infection. Initiate treatment of latent TB prior to administering COSENTYX. Consider anti-TB therapy prior to initiation of COSENTYX in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Patients receiving COSENTYX should be monitored closely for signs and symptoms of active TB during and after treatment.Inflammatory Bowel DiseaseCaution should be used when prescribing COSENTYX to patients with inflammatory bowel disease. Exacerbations, in some cases serious, occurred in patients treated with COSENTYX during clinical trials in plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis. In addition, new onset inflammatory bowel disease cases occurred in clinical trials with COSENTYX. In an exploratory study in 59 patients with active Crohn’s disease, there were trends toward greater disease activity and increased adverse events in the secukinumab group as compared to the placebo group. Patients who are treated with COSENTYX should be monitored for signs and symptoms of inflammatory bowel disease.

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There are a variety of cell types that can produce IL-17A3

IL-17A is an important mediator in the inflammatory process2

Clinical significance of the COSENTYX mechanism of action is unknown. Images not drawn to scale. The above graphic has been simplified. The immune pathophysiology of psoriatic disease involves complex molecular mechanism feedback loops not shown in this graphic.4,5

The understanding of the pathophysiology of plaque psoriasis and psoriatic arthritis continues to evolve.This represents a current theory of the role of IL-17A in the disease.

Please see additional Important Safety Information on adjacent pages.Please see Brief Summary of full Prescribing Information on adjacent pages.

IMPORTANT SAFETY INFORMATION (cont’d)WARNINGS AND PRECAUTIONSInfectionsCOSENTYX may increase the risk of infections. In clinical trials, a higher rate of infections was observed in subjects treated with COSENTYX compared to placebo-treated subjects. In placebo-controlled clinical trials in patients with moderate to severe plaque psoriasis, higher rates of common infections such as nasopharyngitis (11.4% versus 8.6%), upper respiratory tract infection (2.5% versus 0.7%), and mucocutaneous infections with candida (1.2% versus 0.3%) were observed with COSENTYX compared with placebo. A similar increase in risk of infection was seen in placebo-controlled trials in patients with psoriatic arthritis and ankylosing spondylitis. The incidence of some types of infections appeared to be dose-dependent in clinical studies.Exercise caution when considering the use of COSENTYX in patients with a chronic infection or a history of recurrent infection. Instruct patients to seek medical advice if signs or symptoms suggestive of an infection occur. If a patient develops a serious infection, the patient should be closely monitored and COSENTYX should be discontinued until the infection resolves.

IL-17A is a naturally occurring cytokine involved in normal inflammatory and immune response. Selectively targeting IL-17A with COSENTYX® (secukinumab) inhibits release of pro-inflammatory

cytokines and chemokines—which are implicated in the development of certain types of psoriatic disease.2

IL-17A

TH17 cells

IL-23

Activated dendritic cells

TNFα Mast cells

NeutrophilsOther T cells

Innate lymphoid cells

Go deeper into the body of evidence for COSENTYXvisit www.cosentyxHCP.com

Active comparator data in moderate to severe plaque PsO vs two different comparators

Efficacy and safety data in robust clinical trials

11+ years of clinical trial experience worldwide6

12,600+ unique prescribers to date in the US1

COSENTYX clinical data backed by real-world experience

PsO, psoriasis.

IMPORTANT SAFETY INFORMATION (cont’d)WARNINGS AND PRECAUTIONS (cont’d)Pre-treatment Evaluation for Tuberculosis Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with COSENTYX. Do not administer COSENTYX to patients with active TB infection. Initiate treatment of latent TB prior to administering COSENTYX. Consider anti-TB therapy prior to initiation of COSENTYX in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Patients receiving COSENTYX should be monitored closely for signs and symptoms of active TB during and after treatment.Inflammatory Bowel DiseaseCaution should be used when prescribing COSENTYX to patients with inflammatory bowel disease. Exacerbations, in some cases serious, occurred in patients treated with COSENTYX during clinical trials in plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis. In addition, new onset inflammatory bowel disease cases occurred in clinical trials with COSENTYX. In an exploratory study in 59 patients with active Crohn’s disease, there were trends toward greater disease activity and increased adverse events in the secukinumab group as compared to the placebo group. Patients who are treated with COSENTYX should be monitored for signs and symptoms of inflammatory bowel disease.

Page 14: ACR - jmcp.org › pb-assets › Outserts › 18100_ACR...American College of Rheumatology/ Association of Rheumatology Health Professionals 2018 Annual Meeting ACR October 19–24,

is the #1 prescribed interleukin antagonist

across PsO, PsA, and AS7*

* Based on new biologic prescription (NBRx) IMS data week of 9/21/2018. Interleukins include COSENTYX, Stelara® (ustekinumab), Taltz® (ixekizumab), and Tremfya® (guselkumab).

References: 1. Data on file. Cosentyx Tracker Data. Novartis Pharmaceuticals Corp; February 2018. 2. Cosentyx [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2018. 3. Miossec P, Kolls JK. Targeting IL-17 and TH17 cells in chronic inflammation. Nat Rev Drug Disco. 2012;11(10):763-776. 4. Lynde CW, Poulin Y, Vender R, Bourcier M, Khalil S. Interleukin 17A: toward a new understanding of psoriasis pathogenesis. J Am Acad Dermatol. 2014;71(1):141-150. 5. Nestle FO, Kaplan DH, Barker J. Psoriasis. N Engl J Med. 2009;361(5):496-509. 6. Data on file. AIN457A2102 Clinical Study Report. Novartis Pharmaceuticals Corp; December 2008. 7. Data on file. Cosentyx Weekly Dashboard. Novartis Pharmaceuticals Corp; September 21, 2018.

IMPORTANT SAFETY INFORMATION (cont’d)WARNINGS AND PRECAUTIONS (cont’d)Hypersensitivity Reactions Anaphylaxis and cases of urticaria occurred in patients treated with COSENTYX in clinical trials. If an anaphylactic or other serious allergic reaction occurs, administration of COSENTYX should be discontinued immediately and appropriate therapy initiated. The removable cap of the COSENTYX Sensoready® pen and the COSENTYX prefilled syringe contains natural rubber latex which may cause an allergic reaction in latex-sensitive individuals. The safe use of the COSENTYX Sensoready pen or prefilled syringe in latex-sensitive individuals has not been studied.Vaccinations Prior to initiating therapy with COSENTYX, consider completion of all age appropriate immunizations according to current immunization guidelines. Patients treated with COSENTYX should not receive live vaccines.Non-live vaccinations received during a course of COSENTYX may not elicit an immune response sufficient to prevent disease.MOST COMMON ADVERSE REACTIONSMost common adverse reactions (>1%) are nasopharyngitis, diarrhea, and upper respiratory tract infection.

Novartis Pharmaceuticals CorporationEast Hanover, New Jersey 07936-1080 © 2018 Novartis 10/18 T-COS-1364007

Please see additional Important Safety Information on previous pages.Please see Brief Summary of full Prescribing Information on adjacent pages.

AS, ankylosing spondylitis; PsA, psoriatic arthritis; PsO, psoriasis.

COSENTYX® (secukinumab) injection, for subcutaneous use COSENTYX® (secukinumab) for injection, for subcutaneous use Initial U.S. Approval: 2015BRIEF SUMMARY: Please see package insert for full prescribing information. 1 INDICATIONS AND USAGE

1.1 Plaque PsoriasisCOSENTYX® is indicated for the treatment of moderate to severe plaquepsoriasis in adult patients who are candidates for systemic therapy orphototherapy.1.2 Psoriatic ArthritisCOSENTYX is indicated for the treatment of adult patients with activepsoriatic arthritis. 1.3 Ankylosing SpondylitisCOSENTYX is indicated for the treatment of adult patients with activeankylosing spondylitis.

4 CONTRAINDICATIONSCOSENTYX is contraindicated in patients with a previous serious hyper-sensitivity reaction to secukinumab or to any of the excipients [seeWarnings and Precautions (5.4)].

5 WARNINGS AND PRECAUTIONS 5.1 InfectionsCOSENTYX may increase the risk of infections. In clinical trials, a higherrate of infections was observed in COSENTYX treated subjects comparedto placebo-treated subjects. In placebo-controlled clinical trials in patientswith moderate to severe plaque psoriasis, higher rates of common infec-tions such as nasopharyngitis (11.4% versus 8.6%), upper respiratorytract infection (2.5% versus 0.7%) and mucocutaneous infections withcandida (1.2% versus 0.3%) were observed with COSENTYX comparedwith placebo. A similar increase in risk of infection was seen in placebo-controlled trials in patients with psoriatic arthritis and ankylosingspondylitis [see Adverse Reactions (6.1)]. The incidence of some types of infections appeared to be dose-dependent in clinical studies [seeAdverse Reactions (6.1)].Exercise caution when considering the use of COSENTYX in patients witha chronic infection or a history of recurrent infection. Instruct patients to seek medical advice if signs or symptoms suggestiveof an infection occur. If a patient develops a serious infection, the patientshould be closely monitored and COSENTYX should be discontinueduntil the infection resolves.5.2 Pre-treatment Evaluation for TuberculosisEvaluate patients for tuberculosis (TB) infection prior to initiating treat-ment with COSENTYX. Do not administer COSENTYX to patients withactive TB infection. Initiate treatment of latent TB prior to administeringCOSENTYX. Consider anti-TB therapy prior to initiation of COSENTYX inpatients with a past history of latent or active TB in whom an adequatecourse of treatment cannot be confirmed. Patients receiving COSENTYXshould be monitored closely for signs and symptoms of active TB duringand after treatment.5.3 Inflammatory Bowel DiseaseCaution should be used when prescribing COSENTYX to patients withinflammatory bowel disease. Exacerbations, in some cases serious,occurred in COSENTYX treated patients during clinical trials in plaquepsoriasis, psoriatic arthritis and ankylosing spondylitis. In addition, newonset inflammatory bowel disease cases occurred in clinical trials withCOSENTYX. In an exploratory study in 59 patients with active Crohn’sdisease, there were trends toward greater disease activity and increasedadverse events in the secukinumab group as compared to the placebogroup. Patients who are treated with COSENTYX should be monitoredfor signs and symptoms of inflammatory bowel disease [see AdverseReactions (6.1)].5.4 Hypersensitivity ReactionsAnaphylaxis and cases of urticaria occurred in COSENTYX treatedpatients in clinical trials. If an anaphylactic or other serious allergic reac-tion occurs, administration of COSENTYX should be discontinued imme-diately and appropriate therapy initiated [see Adverse Reactions (6.1)].5.5 Risk of Hypersensitivity in Latex-sensitive Individuals The removable cap of the COSENTYX Sensoready pen and the COSENTYXprefilled syringe contains natural rubber latex which may cause an aller-gic reaction in latex-sensitive individuals. The safe use of COSENTYXSenso ready pen or prefilled syringe in latex-sensitive individuals has notbeen studied. 5.6 VaccinationsPrior to initiating therapy with COSENTYX, consider completion of all ageappropriate immunizations according to current immunization guidelines.Patients treated with COSENTYX should not receive live vaccines.Non-live vaccinations received during a course of COSENTYX may notelicit an immune response sufficient to prevent disease.

6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail elsewherein the labeling:• Infections [see Warnings and Precautions (5.1)]

• Inflammatory Bowel Disease [see Warnings and Precautions (5.3)]• Hypersensitivity Reactions [see Warnings and Precautions (5.4)]6.1 Clinical Trials ExperienceBecause clinical trials are conducted under widely varying conditions,adverse reaction rates observed in the clinical trials of a drug cannot bedirectly compared to rates in the clinical trials of another drug and maynot reflect the rates observed in practice.Plaque PsoriasisA total of 3430 plaque psoriasis subjects were treated with COSENTYX incontrolled and uncontrolled clinical trials. Of these, 1641 subjects wereexposed for at least 1 year.Four placebo-controlled phase 3 trials in plaque psoriasis subjects werepooled to evaluate the safety of COSENTYX in comparison to placebo upto 12 weeks after treatment initiation, in Trials 1, 2, 3, and 4. In total,2077 subjects were evaluated (691 to COSENTYX 300 mg group, 692 toCOSENTYX 150 mg group, and 694 to placebo group) [see Clinical Stud-ies (14) in the full prescribing information].Table 1 summarizes the adverse reactions that occurred at a rate of at least1% and at a higher rate in the COSENTYX groups than the placebo groupduring the 12-week placebo-controlled period of the placebo-controlled trials.

Table 1: Adverse Reactions Reported by Greater Than 1% of Subjects withPlaque Psoriasis Through Week 12 in Trials 1, 2, 3, and 4

COSENTYX300 mg 150 mg Placebo

Adverse Reactions (N = 691) (N = 692) (N = 694)n (%) n (%) n (%)

Nasopharyngitis 79 (11.4) 85 (12.3) 60 (8.6)Diarrhea 28 (4.1) 18 (2.6) 10 (1.4)Upper respiratory tract infection 17 (2.5) 22 (3.2) 5 (0.7)

Rhinitis 10 (1.4) 10 (1.4) 5 (0.7)Oral herpes 9 (1.3) 1 (0.1) 2 (0.3)Pharyngitis 8 (1.2) 7 (1.0) 0 (0)Urticaria 4 (0.6) 8 (1.2) 1 (0.1)Rhinorrhea 8 (1.2) 2 (0.3) 1 (0.1)

Adverse reactions that occurred at rates less than 1% in the placebo-controlled period of Trials 1, 2, 3, and 4 through Week 12 included:sinusitis, tinea pedis, conjunctivitis, tonsillitis, oral candidiasis, impetigo,otitis media, otitis externa, inflammatory bowel disease, increased livertransaminases, and neutropenia. InfectionsIn the placebo-controlled period of the clinical trials in plaque psoriasis(a total of 1382 subjects treated with COSENTYX and 694 subjectstreated with placebo up to 12 weeks), infections were reported in 28.7%of subjects treated with COSENTYX compared with 18.9% of subjectstreated with placebo. Serious infections occurred in 0.14% of patientstreated with COSENTYX and in 0.3% of patients treated with placebo[see Warnings and Precautions (5.1)].Over the entire treatment period (a total of 3430 plaque psoriasis subjectstreated with COSENTYX for up to 52 weeks for the majority of subjects),infections were reported in 47.5% of subjects treated with COSENTYX(0.9 per patient-year of follow-up). Serious infections were reported in1.2% of subjects treated with COSENTYX (0.015 per patient-year of follow-up).Phase 3 data showed an increasing trend for some types of infectionwith increasing serum concentration of secukinumab. Candida infec-tions, herpes viral infections, staphylococcal skin infections, and infec-tions requiring treatment increased as serum concentration ofsecukinumab increased. Neutropenia was observed in clinical trials. Most cases of secukinumab-associated neutropenia were transient and reversible. No serious infec-tions were associated with cases of neutropenia.Inflammatory Bowel DiseaseCases of inflammatory bowel disease, in some cases serious, wereobserved in clinical trials with COSENTYX. In the plaque psoriasis pro-gram, with 3430 patients exposed to COSENTYX over the entire treat-ment period for up to 52 weeks (2725 patient-years), there were 3 cases(0.11 per 100 patient-years) of exacerbation of Crohn’s disease, 2 cases(0.08 per 100 patient-years) of exacerbation of ulcerative colitis, and 2 cases (0.08 per 100 patient-years) of new onset ulcerative colitis.There were no cases in placebo patients (N = 793; 176 patient-years)during the 12 week placebo-controlled period. One case of exacerbation of Crohn’s disease was reported from long-term non-controlled portions of ongoing clinical trials in plaque psoriasis[see Warnings and Precautions (5.3)].Hypersensitivity ReactionsAnaphylaxis and cases of urticaria occurred in COSENTYX treatedpatients in clinical trials [see Warnings and Precautions (5.4)].

Page 15: ACR - jmcp.org › pb-assets › Outserts › 18100_ACR...American College of Rheumatology/ Association of Rheumatology Health Professionals 2018 Annual Meeting ACR October 19–24,

is the #1 prescribed interleukin antagonist

across PsO, PsA, and AS7*

* Based on new biologic prescription (NBRx) IMS data week of 9/21/2018. Interleukins include COSENTYX, Stelara® (ustekinumab), Taltz® (ixekizumab), and Tremfya® (guselkumab).

References: 1. Data on file. Cosentyx Tracker Data. Novartis Pharmaceuticals Corp; February 2018. 2. Cosentyx [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2018. 3. Miossec P, Kolls JK. Targeting IL-17 and TH17 cells in chronic inflammation. Nat Rev Drug Disco. 2012;11(10):763-776. 4. Lynde CW, Poulin Y, Vender R, Bourcier M, Khalil S. Interleukin 17A: toward a new understanding of psoriasis pathogenesis. J Am Acad Dermatol. 2014;71(1):141-150. 5. Nestle FO, Kaplan DH, Barker J. Psoriasis. N Engl J Med. 2009;361(5):496-509. 6. Data on file. AIN457A2102 Clinical Study Report. Novartis Pharmaceuticals Corp; December 2008. 7. Data on file. Cosentyx Weekly Dashboard. Novartis Pharmaceuticals Corp; September 21, 2018.

IMPORTANT SAFETY INFORMATION (cont’d)WARNINGS AND PRECAUTIONS (cont’d)Hypersensitivity Reactions Anaphylaxis and cases of urticaria occurred in patients treated with COSENTYX in clinical trials. If an anaphylactic or other serious allergic reaction occurs, administration of COSENTYX should be discontinued immediately and appropriate therapy initiated. The removable cap of the COSENTYX Sensoready® pen and the COSENTYX prefilled syringe contains natural rubber latex which may cause an allergic reaction in latex-sensitive individuals. The safe use of the COSENTYX Sensoready pen or prefilled syringe in latex-sensitive individuals has not been studied.Vaccinations Prior to initiating therapy with COSENTYX, consider completion of all age appropriate immunizations according to current immunization guidelines. Patients treated with COSENTYX should not receive live vaccines.Non-live vaccinations received during a course of COSENTYX may not elicit an immune response sufficient to prevent disease.MOST COMMON ADVERSE REACTIONSMost common adverse reactions (>1%) are nasopharyngitis, diarrhea, and upper respiratory tract infection.

Novartis Pharmaceuticals CorporationEast Hanover, New Jersey 07936-1080 © 2018 Novartis 10/18 T-COS-1364007

Please see additional Important Safety Information on previous pages.Please see Brief Summary of full Prescribing Information on adjacent pages.

AS, ankylosing spondylitis; PsA, psoriatic arthritis; PsO, psoriasis.

COSENTYX® (secukinumab) injection, for subcutaneous use COSENTYX® (secukinumab) for injection, for subcutaneous use Initial U.S. Approval: 2015BRIEF SUMMARY: Please see package insert for full prescribing information. 1 INDICATIONS AND USAGE

1.1 Plaque PsoriasisCOSENTYX® is indicated for the treatment of moderate to severe plaquepsoriasis in adult patients who are candidates for systemic therapy orphototherapy.1.2 Psoriatic ArthritisCOSENTYX is indicated for the treatment of adult patients with activepsoriatic arthritis. 1.3 Ankylosing SpondylitisCOSENTYX is indicated for the treatment of adult patients with activeankylosing spondylitis.

4 CONTRAINDICATIONSCOSENTYX is contraindicated in patients with a previous serious hyper-sensitivity reaction to secukinumab or to any of the excipients [seeWarnings and Precautions (5.4)].

5 WARNINGS AND PRECAUTIONS 5.1 InfectionsCOSENTYX may increase the risk of infections. In clinical trials, a higherrate of infections was observed in COSENTYX treated subjects comparedto placebo-treated subjects. In placebo-controlled clinical trials in patientswith moderate to severe plaque psoriasis, higher rates of common infec-tions such as nasopharyngitis (11.4% versus 8.6%), upper respiratorytract infection (2.5% versus 0.7%) and mucocutaneous infections withcandida (1.2% versus 0.3%) were observed with COSENTYX comparedwith placebo. A similar increase in risk of infection was seen in placebo-controlled trials in patients with psoriatic arthritis and ankylosingspondylitis [see Adverse Reactions (6.1)]. The incidence of some types of infections appeared to be dose-dependent in clinical studies [seeAdverse Reactions (6.1)].Exercise caution when considering the use of COSENTYX in patients witha chronic infection or a history of recurrent infection. Instruct patients to seek medical advice if signs or symptoms suggestiveof an infection occur. If a patient develops a serious infection, the patientshould be closely monitored and COSENTYX should be discontinueduntil the infection resolves.5.2 Pre-treatment Evaluation for TuberculosisEvaluate patients for tuberculosis (TB) infection prior to initiating treat-ment with COSENTYX. Do not administer COSENTYX to patients withactive TB infection. Initiate treatment of latent TB prior to administeringCOSENTYX. Consider anti-TB therapy prior to initiation of COSENTYX inpatients with a past history of latent or active TB in whom an adequatecourse of treatment cannot be confirmed. Patients receiving COSENTYXshould be monitored closely for signs and symptoms of active TB duringand after treatment.5.3 Inflammatory Bowel DiseaseCaution should be used when prescribing COSENTYX to patients withinflammatory bowel disease. Exacerbations, in some cases serious,occurred in COSENTYX treated patients during clinical trials in plaquepsoriasis, psoriatic arthritis and ankylosing spondylitis. In addition, newonset inflammatory bowel disease cases occurred in clinical trials withCOSENTYX. In an exploratory study in 59 patients with active Crohn’sdisease, there were trends toward greater disease activity and increasedadverse events in the secukinumab group as compared to the placebogroup. Patients who are treated with COSENTYX should be monitoredfor signs and symptoms of inflammatory bowel disease [see AdverseReactions (6.1)].5.4 Hypersensitivity ReactionsAnaphylaxis and cases of urticaria occurred in COSENTYX treatedpatients in clinical trials. If an anaphylactic or other serious allergic reac-tion occurs, administration of COSENTYX should be discontinued imme-diately and appropriate therapy initiated [see Adverse Reactions (6.1)].5.5 Risk of Hypersensitivity in Latex-sensitive Individuals The removable cap of the COSENTYX Sensoready pen and the COSENTYXprefilled syringe contains natural rubber latex which may cause an aller-gic reaction in latex-sensitive individuals. The safe use of COSENTYXSenso ready pen or prefilled syringe in latex-sensitive individuals has notbeen studied. 5.6 VaccinationsPrior to initiating therapy with COSENTYX, consider completion of all ageappropriate immunizations according to current immunization guidelines.Patients treated with COSENTYX should not receive live vaccines.Non-live vaccinations received during a course of COSENTYX may notelicit an immune response sufficient to prevent disease.

6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail elsewherein the labeling:• Infections [see Warnings and Precautions (5.1)]

• Inflammatory Bowel Disease [see Warnings and Precautions (5.3)]• Hypersensitivity Reactions [see Warnings and Precautions (5.4)]6.1 Clinical Trials ExperienceBecause clinical trials are conducted under widely varying conditions,adverse reaction rates observed in the clinical trials of a drug cannot bedirectly compared to rates in the clinical trials of another drug and maynot reflect the rates observed in practice.Plaque PsoriasisA total of 3430 plaque psoriasis subjects were treated with COSENTYX incontrolled and uncontrolled clinical trials. Of these, 1641 subjects wereexposed for at least 1 year.Four placebo-controlled phase 3 trials in plaque psoriasis subjects werepooled to evaluate the safety of COSENTYX in comparison to placebo upto 12 weeks after treatment initiation, in Trials 1, 2, 3, and 4. In total,2077 subjects were evaluated (691 to COSENTYX 300 mg group, 692 toCOSENTYX 150 mg group, and 694 to placebo group) [see Clinical Stud-ies (14) in the full prescribing information].Table 1 summarizes the adverse reactions that occurred at a rate of at least1% and at a higher rate in the COSENTYX groups than the placebo groupduring the 12-week placebo-controlled period of the placebo-controlled trials.

Table 1: Adverse Reactions Reported by Greater Than 1% of Subjects withPlaque Psoriasis Through Week 12 in Trials 1, 2, 3, and 4

COSENTYX300 mg 150 mg Placebo

Adverse Reactions (N = 691) (N = 692) (N = 694)n (%) n (%) n (%)

Nasopharyngitis 79 (11.4) 85 (12.3) 60 (8.6)Diarrhea 28 (4.1) 18 (2.6) 10 (1.4)Upper respiratory tract infection 17 (2.5) 22 (3.2) 5 (0.7)

Rhinitis 10 (1.4) 10 (1.4) 5 (0.7)Oral herpes 9 (1.3) 1 (0.1) 2 (0.3)Pharyngitis 8 (1.2) 7 (1.0) 0 (0)Urticaria 4 (0.6) 8 (1.2) 1 (0.1)Rhinorrhea 8 (1.2) 2 (0.3) 1 (0.1)

Adverse reactions that occurred at rates less than 1% in the placebo-controlled period of Trials 1, 2, 3, and 4 through Week 12 included:sinusitis, tinea pedis, conjunctivitis, tonsillitis, oral candidiasis, impetigo,otitis media, otitis externa, inflammatory bowel disease, increased livertransaminases, and neutropenia. InfectionsIn the placebo-controlled period of the clinical trials in plaque psoriasis(a total of 1382 subjects treated with COSENTYX and 694 subjectstreated with placebo up to 12 weeks), infections were reported in 28.7%of subjects treated with COSENTYX compared with 18.9% of subjectstreated with placebo. Serious infections occurred in 0.14% of patientstreated with COSENTYX and in 0.3% of patients treated with placebo[see Warnings and Precautions (5.1)].Over the entire treatment period (a total of 3430 plaque psoriasis subjectstreated with COSENTYX for up to 52 weeks for the majority of subjects),infections were reported in 47.5% of subjects treated with COSENTYX(0.9 per patient-year of follow-up). Serious infections were reported in1.2% of subjects treated with COSENTYX (0.015 per patient-year of follow-up).Phase 3 data showed an increasing trend for some types of infectionwith increasing serum concentration of secukinumab. Candida infec-tions, herpes viral infections, staphylococcal skin infections, and infec-tions requiring treatment increased as serum concentration ofsecukinumab increased. Neutropenia was observed in clinical trials. Most cases of secukinumab-associated neutropenia were transient and reversible. No serious infec-tions were associated with cases of neutropenia.Inflammatory Bowel DiseaseCases of inflammatory bowel disease, in some cases serious, wereobserved in clinical trials with COSENTYX. In the plaque psoriasis pro-gram, with 3430 patients exposed to COSENTYX over the entire treat-ment period for up to 52 weeks (2725 patient-years), there were 3 cases(0.11 per 100 patient-years) of exacerbation of Crohn’s disease, 2 cases(0.08 per 100 patient-years) of exacerbation of ulcerative colitis, and 2 cases (0.08 per 100 patient-years) of new onset ulcerative colitis.There were no cases in placebo patients (N = 793; 176 patient-years)during the 12 week placebo-controlled period. One case of exacerbation of Crohn’s disease was reported from long-term non-controlled portions of ongoing clinical trials in plaque psoriasis[see Warnings and Precautions (5.3)].Hypersensitivity ReactionsAnaphylaxis and cases of urticaria occurred in COSENTYX treatedpatients in clinical trials [see Warnings and Precautions (5.4)].

Page 16: ACR - jmcp.org › pb-assets › Outserts › 18100_ACR...American College of Rheumatology/ Association of Rheumatology Health Professionals 2018 Annual Meeting ACR October 19–24,

Psoriatic ArthritisCOSENTYX was studied in two placebo-controlled psoriatic arthritis trialswith 1003 patients (703 patients on COSENTYX and 300 patients onplacebo). Of the 703 patients who received COSENTYX, 299 patientsreceived a subcutaneous loading dose of COSENTYX (PsA1) and 404 patients received an intravenous loading dose of secukinumab (PsA2)followed by COSENTYX administered by subcutaneous injection every fourweeks. During the 16-week placebo-controlled period of the trials inpatients with psoriatic arthritis, the overall proportion of patients withadverse events was similar in the secukinumab and placebo-treatmentgroups (59% and 58%, respectively). The adverse events that occurred ata proportion of at least 2% and at a higher proportion in the COSENTYXgroups than the placebo groups during the 16-week placebo-controlledperiod were nasopharyngitis, upper respiratory tract infection, headache,nausea, and hypercholesterolemia. The safety profile observed in patientswith psoriatic arthritis treated with COSENTYX is consistent with the safetyprofile in psoriasis. Similar to the clinical trials in patients with psoriasis, there was anincreased proportion of patients with infections in the COSENTYXgroups (29%) compared to placebo group (26%) [see Warnings andPrecautions (5.1)]. There were cases of Crohn’s disease and ulcerative colitis that includepatients who experienced either exacerbations or the development of newdisease. There were three cases of inflammatory bowel disease, of whichtwo patients received secukinumab and one received placebo [see Warn-ings and Precautions (5.3)].Ankylosing SpondylitisCOSENTYX was studied in two placebo controlled ankylosing spondylitistrials with 590 patients (394 patients on COSENTYX and 196 patients onplacebo). Of the 394 patients who received COSENTYX, 145 patientsreceived a subcutaneous load of COSENTYX (study AS1) and 249 receivedan intravenous loading dose of secukinumab (study AS2) followed byCOSENTYX administered by subcutaneous injection every four weeks.During the 16-week placebo-controlled period of the trials in patients withankylosing spondylitis, the overall proportion of patients with adverseevents was higher in the secukinumab groups than the placebo-treatmentgroups (66% and 59%, respectively). The adverse events that occurred ata proportion of at least 2% and at a higher proportion in the COSENTYXgroups than the placebo groups during the 16-week placebo-controlledperiod were nasopharyngitis, nausea, and upper respiratory tract infection.The safety profile observed in patients with ankylosing spondylitis treatedwith COSENTYX is consistent with the safety profile in psoriasis.Similar to clinical trials in patients with psoriasis, there was an increasedproportion of patients with infections in the COSENTYX groups (31%)compared to the placebo group (18%) [see Warnings and Precautions(5.1)].In the ankylosing spondylitis program, with 571 patients exposed toCOSENTYX there were 8 cases of inflammatory bowel disease during theentire treatment period [5 Crohn’s (0.7 per 100 patient-years) and 3 ulcer-ative colitis (0.4 per 100 patient-years)]. During the placebo-controlled16-week period, there were 2 Crohn’s disease exacerbations and 1 newonset ulcerative colitis case that was a serious adverse event in patientstreated with COSENTYX compared to none of the patients treated withplacebo. During the remainder of the study when all patients receivedCOSENTYX, 1 patient developed Crohn’s disease, 2 patients had Crohn’sexacerbations, 1 patient developed ulcerative colitis, and 1 patient had anulcerative colitis exacerbation [see Warnings and Precautions (5.3)].6.2 ImmunogenicityAs with all therapeutic proteins, there is the potential for immuno -genicity. The immunogenicity of COSENTYX was evaluated using anelectrochemiluminescence-based bridging immunoassay. Less than 1%of subjects treated with COSENTYX developed antibodies to secukinumabin up to 52 weeks of treatment. However, this assay has limitations indetecting anti-secukinumab antibodies in the presence of secukinumab;therefore the incidence of antibody development might not have been reliably determined. Of the subjects who developed antidrug antibodies,approximately one-half had antibodies that were classified as neutralizing.Neutralizing antibodies were not associated with loss of efficacy. The detection of antibody formation is highly dependent on the sensitivityand specificity of the assay. Additionally, the observed incidence of anti-body (including neutralizing antibody) positivity in an assay may be influ-enced by several factors including assay methodology, sample handling,timing of sample collection, concomitant medications, and underlyingdisease. For these reasons, comparison of incidence of antibodies toCOSENTYX with the incidences of antibodies to other products may bemisleading.

7 DRUG INTERACTIONS 7.1 Live VaccinesPatients treated with COSENTYX may not receive live vaccinations [seeWarnings and Precautions (5.6)]. 7.2 Non-Live VaccinesPatients treated with COSENTYX may receive non-live vaccinations.Healthy individuals who received a single 150 mg dose of COSENTYX

2 weeks prior to vaccination with a non-U.S. approved group Cmeningococcal polysaccharide conjugate vaccine and a non-U.S.approved inactivated seasonal influenza vaccine had similar antibodyresponses compared to individuals who did not receive COSENTYX priorto vaccination. The clinical effectiveness of meningococcal and influenzavaccines has not been assessed in patients undergoing treatment withCOSENTYX [see Warnings and Precautions (5.6)]. 7.3 CYP450 SubstratesThe formation of CYP450 enzymes can be altered by increased levels ofcertain cytokines (e.g., IL-1, IL-6, IL-10, TNFα, IFN) during chronicinflammation. Results from a drug-drug interaction study in subjects with moderate tosevere psoriasis showed no clinically relevant interaction for drugsmetabolized by CYP3A4.Upon initiation or discontinuation of COSENTYX in patients who arereceiving concomitant CYP450 substrates, particularly those with a nar-row therapeutic index, consider monitoring for therapeutic effect or drugconcentration and consider dosage adjustment as needed [see ClinicalPharmacology (12.3) in the full prescribing information].

8 USE IN SPECIFIC POPULATIONS 8.1 PregnancyRisk SummaryLimited available human data with COSENTYX use in pregnant womenare insufficient to inform a drug associated risk of adverse developmen-tal outcomes. In an embryo-fetal development study, no adverse devel-opmental effects were observed in infants born to pregnant monkeysafter subcutaneous administration of secukinumab during organo -genesis at doses up to 30 times the maximum recommended humandose (MRHD) (see Data). The background risk of major birth defects and miscarriage for the indi-cated population is unknown; however, the background risk in the U.S.general population of major birth defects is 2%-4% and of miscarriage is15%-20% of clinically recognized pregnancies.DataAnimal DataAn embryo-fetal development study was performed in cynomolgus mon-keys with secukinumab. No malformations or embryo-fetal toxicity wereobserved in fetuses from pregnant monkeys that were administeredsecukinumab weekly by the subcutaneous route during the period oforganogenesis at doses up to 30 times the MRHD (on a mg/kg basis at a maternal dose of 150 mg/kg).A pre- and post-natal development toxicity study was performed in micewith a murine analog of secukinumab. No treatment related effects onfunctional, morphological or immunological development were observedin fetuses from pregnant mice that were administered the murine analogof secukinumab on gestation days 6, 11, and 17 and on postpartum days 4, 10, and 16 at doses up to 150 mg/kg/dose.8.2 LactationRisk SummaryIt is not known whether secukinumab is excreted in human milk orabsorbed systemically after ingestion. There are no data on the effects ofCOSENTYX on the breastfed child or the effects on milk production. Thedevelopmental and health benefits of breastfeeding should be consideredalong with the mother’s clinical need for COSENTYX and any potentialadverse effects on the breastfed child from COSENTYX or from theunderlying maternal condition. 8.4 Pediatric UseSafety and effectiveness of COSENTYX in pediatric patients have notbeen evaluated.8.5 Geriatric UseOf the 3430 plaque psoriasis subjects exposed to COSENTYX in clinical tri-als, a total of 230 were 65 years or older, and 32 subjects were 75 years orolder. Although no differences in safety or efficacy were observed betweenolder and younger subjects, the number of subjects aged 65 years andolder was not sufficient to determine whether they responded differentlyfrom younger subjects.

10 OVERDOSAGEDoses up to 30 mg/kg intravenously have been administered in clinicaltrials without dose-limiting toxicity. In the event of overdosage, it is rec-ommended that the patient be monitored for any signs or symptoms ofadverse reactions and appropriate symptomatic treatment be institutedimmediately.

Manufactured by:Novartis Pharmaceuticals CorporationEast Hanover, New Jersey 07936US License No. 1244

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Psoriatic ArthritisCOSENTYX was studied in two placebo-controlled psoriatic arthritis trialswith 1003 patients (703 patients on COSENTYX and 300 patients onplacebo). Of the 703 patients who received COSENTYX, 299 patientsreceived a subcutaneous loading dose of COSENTYX (PsA1) and 404 patients received an intravenous loading dose of secukinumab (PsA2)followed by COSENTYX administered by subcutaneous injection every fourweeks. During the 16-week placebo-controlled period of the trials inpatients with psoriatic arthritis, the overall proportion of patients withadverse events was similar in the secukinumab and placebo-treatmentgroups (59% and 58%, respectively). The adverse events that occurred ata proportion of at least 2% and at a higher proportion in the COSENTYXgroups than the placebo groups during the 16-week placebo-controlledperiod were nasopharyngitis, upper respiratory tract infection, headache,nausea, and hypercholesterolemia. The safety profile observed in patientswith psoriatic arthritis treated with COSENTYX is consistent with the safetyprofile in psoriasis. Similar to the clinical trials in patients with psoriasis, there was anincreased proportion of patients with infections in the COSENTYXgroups (29%) compared to placebo group (26%) [see Warnings andPrecautions (5.1)]. There were cases of Crohn’s disease and ulcerative colitis that includepatients who experienced either exacerbations or the development of newdisease. There were three cases of inflammatory bowel disease, of whichtwo patients received secukinumab and one received placebo [see Warn-ings and Precautions (5.3)].Ankylosing SpondylitisCOSENTYX was studied in two placebo controlled ankylosing spondylitistrials with 590 patients (394 patients on COSENTYX and 196 patients onplacebo). Of the 394 patients who received COSENTYX, 145 patientsreceived a subcutaneous load of COSENTYX (study AS1) and 249 receivedan intravenous loading dose of secukinumab (study AS2) followed byCOSENTYX administered by subcutaneous injection every four weeks.During the 16-week placebo-controlled period of the trials in patients withankylosing spondylitis, the overall proportion of patients with adverseevents was higher in the secukinumab groups than the placebo-treatmentgroups (66% and 59%, respectively). The adverse events that occurred ata proportion of at least 2% and at a higher proportion in the COSENTYXgroups than the placebo groups during the 16-week placebo-controlledperiod were nasopharyngitis, nausea, and upper respiratory tract infection.The safety profile observed in patients with ankylosing spondylitis treatedwith COSENTYX is consistent with the safety profile in psoriasis.Similar to clinical trials in patients with psoriasis, there was an increasedproportion of patients with infections in the COSENTYX groups (31%)compared to the placebo group (18%) [see Warnings and Precautions(5.1)].In the ankylosing spondylitis program, with 571 patients exposed toCOSENTYX there were 8 cases of inflammatory bowel disease during theentire treatment period [5 Crohn’s (0.7 per 100 patient-years) and 3 ulcer-ative colitis (0.4 per 100 patient-years)]. During the placebo-controlled16-week period, there were 2 Crohn’s disease exacerbations and 1 newonset ulcerative colitis case that was a serious adverse event in patientstreated with COSENTYX compared to none of the patients treated withplacebo. During the remainder of the study when all patients receivedCOSENTYX, 1 patient developed Crohn’s disease, 2 patients had Crohn’sexacerbations, 1 patient developed ulcerative colitis, and 1 patient had anulcerative colitis exacerbation [see Warnings and Precautions (5.3)].6.2 ImmunogenicityAs with all therapeutic proteins, there is the potential for immuno -genicity. The immunogenicity of COSENTYX was evaluated using anelectrochemiluminescence-based bridging immunoassay. Less than 1%of subjects treated with COSENTYX developed antibodies to secukinumabin up to 52 weeks of treatment. However, this assay has limitations indetecting anti-secukinumab antibodies in the presence of secukinumab;therefore the incidence of antibody development might not have been reliably determined. Of the subjects who developed antidrug antibodies,approximately one-half had antibodies that were classified as neutralizing.Neutralizing antibodies were not associated with loss of efficacy. The detection of antibody formation is highly dependent on the sensitivityand specificity of the assay. Additionally, the observed incidence of anti-body (including neutralizing antibody) positivity in an assay may be influ-enced by several factors including assay methodology, sample handling,timing of sample collection, concomitant medications, and underlyingdisease. For these reasons, comparison of incidence of antibodies toCOSENTYX with the incidences of antibodies to other products may bemisleading.

7 DRUG INTERACTIONS 7.1 Live VaccinesPatients treated with COSENTYX may not receive live vaccinations [seeWarnings and Precautions (5.6)]. 7.2 Non-Live VaccinesPatients treated with COSENTYX may receive non-live vaccinations.Healthy individuals who received a single 150 mg dose of COSENTYX

2 weeks prior to vaccination with a non-U.S. approved group Cmeningococcal polysaccharide conjugate vaccine and a non-U.S.approved inactivated seasonal influenza vaccine had similar antibodyresponses compared to individuals who did not receive COSENTYX priorto vaccination. The clinical effectiveness of meningococcal and influenzavaccines has not been assessed in patients undergoing treatment withCOSENTYX [see Warnings and Precautions (5.6)]. 7.3 CYP450 SubstratesThe formation of CYP450 enzymes can be altered by increased levels ofcertain cytokines (e.g., IL-1, IL-6, IL-10, TNFα, IFN) during chronicinflammation. Results from a drug-drug interaction study in subjects with moderate tosevere psoriasis showed no clinically relevant interaction for drugsmetabolized by CYP3A4.Upon initiation or discontinuation of COSENTYX in patients who arereceiving concomitant CYP450 substrates, particularly those with a nar-row therapeutic index, consider monitoring for therapeutic effect or drugconcentration and consider dosage adjustment as needed [see ClinicalPharmacology (12.3) in the full prescribing information].

8 USE IN SPECIFIC POPULATIONS 8.1 PregnancyRisk SummaryLimited available human data with COSENTYX use in pregnant womenare insufficient to inform a drug associated risk of adverse developmen-tal outcomes. In an embryo-fetal development study, no adverse devel-opmental effects were observed in infants born to pregnant monkeysafter subcutaneous administration of secukinumab during organo -genesis at doses up to 30 times the maximum recommended humandose (MRHD) (see Data). The background risk of major birth defects and miscarriage for the indi-cated population is unknown; however, the background risk in the U.S.general population of major birth defects is 2%-4% and of miscarriage is15%-20% of clinically recognized pregnancies.DataAnimal DataAn embryo-fetal development study was performed in cynomolgus mon-keys with secukinumab. No malformations or embryo-fetal toxicity wereobserved in fetuses from pregnant monkeys that were administeredsecukinumab weekly by the subcutaneous route during the period oforganogenesis at doses up to 30 times the MRHD (on a mg/kg basis at a maternal dose of 150 mg/kg).A pre- and post-natal development toxicity study was performed in micewith a murine analog of secukinumab. No treatment related effects onfunctional, morphological or immunological development were observedin fetuses from pregnant mice that were administered the murine analogof secukinumab on gestation days 6, 11, and 17 and on postpartum days 4, 10, and 16 at doses up to 150 mg/kg/dose.8.2 LactationRisk SummaryIt is not known whether secukinumab is excreted in human milk orabsorbed systemically after ingestion. There are no data on the effects ofCOSENTYX on the breastfed child or the effects on milk production. Thedevelopmental and health benefits of breastfeeding should be consideredalong with the mother’s clinical need for COSENTYX and any potentialadverse effects on the breastfed child from COSENTYX or from theunderlying maternal condition. 8.4 Pediatric UseSafety and effectiveness of COSENTYX in pediatric patients have notbeen evaluated.8.5 Geriatric UseOf the 3430 plaque psoriasis subjects exposed to COSENTYX in clinical tri-als, a total of 230 were 65 years or older, and 32 subjects were 75 years orolder. Although no differences in safety or efficacy were observed betweenolder and younger subjects, the number of subjects aged 65 years andolder was not sufficient to determine whether they responded differentlyfrom younger subjects.

10 OVERDOSAGEDoses up to 30 mg/kg intravenously have been administered in clinicaltrials without dose-limiting toxicity. In the event of overdosage, it is rec-ommended that the patient be monitored for any signs or symptoms ofadverse reactions and appropriate symptomatic treatment be institutedimmediately.

Manufactured by:Novartis Pharmaceuticals CorporationEast Hanover, New Jersey 07936US License No. 1244

© Novartis

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Treatment of Patients with AS, PsA, and PsO

During the annual meeting, a standing-room-only audience attended a product theater on Cosentyx® (secukinumab), manufactured by Novartis, which

is used to treat several forms of spondyloarthritis. Sergio Schwartzman, MD, of Weill Cornell Medical College and NewYork-Presbyterian Hospital and Hospital for Special Surgery, presented “Going Deeper into the Body of Evi-dence: Cosentyx for the Treatment of patients with AS, PsA, and PsO.”

Dr. Schwartzman noted that the field of rheumatology changed dramatically in 1998, when the first biologics were approved for rheumatologic diseases by the U.S. Food and Drug Administration. Since then, industry has created a number of agents for different targets in rheu-matologic disease states. Secukinumab is the first and only drug approved as an anti–interleukin (IL)-17 therapy for three indications: ankylosing spondylitis (AS), psoriatic arthritis (PsA), and psoriasis (PsO). The drug is a human monoclonal antibody that inhibits the action of IL-17A, which is overexpressed in people with spondyloarthritis.

The presentation reviewed the treatment’s important safety information and contraindications. Although Dr. Schwartzman stressed that there are no boxed warnings, he said patients receiving secukinumab have a slightly increased risk of infection, so physicians should monitor patients for signs of infection throughout treatment, in addition to pre-testing patients for tuberculosis. Also, Dr. Schwartzman cautioned that IL-17 is overexpressed in the bowels of patients with inflammatory bowel disease (IBD), so studies have found a trend of worsening IBD with secukinumab.

SECUKINUMAB FOR ASInflammatory back pain caused by sacroiliitis and inflam-mation at other locations in the axial skeleton is the main clinical feature in patients with AS, Dr. Schwartzman said. Patients experience spinal stiffness, often in the morning, as well as loss of spinal mobility. Disease-related factors significantly impact their health-related quality of life, he said, but diagnosis is often delayed by 8 to 12 years because patients see primary care physicians and specialists such as orthopaedists first.

In the MEASURE 2 study, which assessed the efficacy and safety of secukinumab in patients with active AS, up to 68% of patients had reduced disease activity at week 16, with improvements in spinal mobility and quality of life. Follow-up studies found a consistent response rate at 4 years. In addition, inflammation dropped as measured by high-sensitivity C-reactive protein levels at week 16 and at 4 years. Patients achieved inactive disease as early as 1 year, which was sustained through 4 years.

The most common safety issues associated with secukinumab were increased rates of nasopharyngitis, up-per respiratory tract infections, and nausea. Serious infec-tions are possible, Dr. Schwartzman said, so patients should be monitored. For example, Crohn’s disease and ulcerative colitis can occur, but this is rare. Secukinumab’s safety profile remained consistent through 4 years.

SECUKINUMAB FOR PSA PsA contains multiple different phenotypes, Dr. Schwartz-man said, and patients experience significant effects on morbidity and functional status. They also are at risk for structural damage. He reviewed results from the FUTURE 2 and FUTURE 5 clinical trials, which studied safety, tolerabil-ity, and efficacy of secukinumab in patients with active PsA.

Patients experienced quick relief compared with placebo as early as the third week of treatment, and they maintained strong response rates at 4 years, he said. They also had significant improvements and high rates of complete resolution of enthesitis and dactylitis through 4 years. Furthermore, radiographic data showed inhibition of structural progression.

Dr. Schwartzman said, the most common adverse events were nasopharyngitis, upper respiratory tract infec-tion, headache, nausea, and hypercholesterolemia.

SECUKINUMAB FOR PSOThe final study reviewed during the presentation examined secukinumab in PsO. The ERASURE and FIXTURE stud-ies examined the efficacy and safety of secukinumab in moderate to severe chronic plaque-type PsO. Researchers documented significant clearance of the skin, and safety

Since 1998, industry has created a number of agents for different targets in rheumatologic disease states.

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was similar to that observed in the other disease states. Efficacy and safety were maintained through 52 weeks. The TRANSFIGURE study has demonstrated secukinumab’s efficacy in nail psoriasis, Dr. Schwartzman said, although results can appear slow because damaged nails need a year to regenerate and get back to normal.

SECUKINUMAB DOSINGSecukinumab is administered via SensoReady® Pen45, which features no-push activation, a concealed needle, and a viewing window to ensure complete delivery of the medi-cation. Recommended dosing is as follows, Dr. Schwartz-man said:

• The medication is given once a week for 5 weeks, then every 4 weeks thereafter.

• Patients with AS: 150 mg with or without a loading dose

• Patients with PsA without moderate to severe PsO: 150 mg, with possible escalation to 300 mg, with or without a loading dose. This can be done with or with-out methotrexate, he said.

• Patients with moderate to severe PsO with or without PsA: 300 mg in two subcutaneous 150 mg injections; 150 mg may be acceptable in some patients, he said.

CONCLUSIONDr. Schwartzman concluded by saying that secukinumab has demonstrated efficacy across several disease manifes-tations. Patients with AS showed improvement in axial disease as early as 4 weeks, as well as increased mobility, and response rates have been consistent through 4 years. In PsA, the treatment has improved multiple domains. Re-garding peripheral arthritis, patients had strong response rates as early as 3 weeks, and response lasted through 4 years. In addition, the treatment inhibited progression of joint structural damage at 1 year. Patients with PsA also had complete resolution of enthesitis and dactylitis at 1 year and through 4 years. Finally, most patients with plaque PsO had clear or almost clear skin at week 12 of treatment; those with moderate to severe nail PsO saw a reduction at week 16 and through week 132.

In addition, the newest research has found that responses are enduring through 4 years, with similar safety profiles. ●

Women Abused During Childhood Have Significantly Higher Risk of Lupus

According to research presented at the annual meeting, women who experienced physical or emotional abuse in childhood have a significantly

higher risk of developing systemic lupus erythematosus (SLE) in adulthood.

SLE is a chronic disease that causes systemic inflamma-tion that affects multiple organs. It is far more common in women than men. Past research has shown associations between post-traumatic stress disorder and increased risk of SLE, as well as between childhood adverse events and higher risk for hospitalization due to autoimmune disease. Therefore, researchers from Brigham and Women’s Hos-pital/Harvard Medical School and the Harvard T.H. Chan School of Public Health in Boston examined correlations between childhood abuse and SLE risk.

The research team examined data on 67,434 women from the Nurses’ Health Study II, a longitudinal cohort of female nurses in the United States. The researchers as-sessed whether the nurses had experienced physical abuse, emotional maltreatment, or sexual abuse in childhood, per the nurses’ completion in 2001 of the Physical and Emo-tional Abuse Subscale of the Childhood Trauma Question-naire, the Conflict Tactics Scale, and the Sexual Maltreat-ment Scale of the Parent-Child Conflicts Tactics Scale.

The researchers then identified new SLE cases among the cohort through 2015 via self-report of physician diag-noses, which then were confirmed by two rheumatologists via medical record review. Finally, the researchers evalu-ated the association between childhood abuse and risk of developing SLE, accounting for potential confounders and other risk factors, such as smoking, body mass index, and parents’ socioeconomic status.

There were 93 cases of SLE. Patients who were exposed to the highest levels of physical and emotional abuse had a more than twofold greater risk of developing SLE compared with patients who were exposed to the lowest levels of such abuse. Those who were exposed to moderate or high levels of physical assault had a 1.70 times higher risk of SLE compared with those who had no exposure to assault. The research did not find a statistically significant association between sexual abuse and risk of SLE.

“The strong association observed between childhood abuse and lupus risk suggests the need for further re-search to understand biological and behavioral changes triggered by stress combined with other environmental

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exposures,” said lead author Candace H. Feldman, MD, ScD, of Harvard Medical School. “In addition, physicians should consider screening their patients for experiences of childhood abuse and trauma.” ●

Study Finds That Intensity of Walking Affects Risk of Knee Replacement

Patients with knee osteoarthritis (OA) who walk with moderate to vigorous intensity may lower their risk of total knee arthroplasty (TKA), according to new

research presented at the annual meeting. OA is a common, painful joint disease that usually af-

fects people during middle age or later. It is characterized by a breakdown of the cartilage, bony changes in joints, deterioration of tendons and ligaments, and inflammation of the synovium. Knee arthroplasty, or joint replacement, is a common treatment for knee OA.

The researchers sought to explore whether walking more increases a patient’s risk of further structural dam-age in the knee joint and therefore risk of TKA. Although previous research has been conducted on the topic, the team from the University of Delaware suspected that different levels of walking intensity may have contributed to contradictory evidence. Therefore, they conducted a 5-year study to reveal associations between walking intensity and TKA in adult patients who had or were at risk for knee OA.

“Walking may exacerbate knee pain and further make things worse, but on the other hand, walking is helpful to build and maintain strength and may prevent the develop-ment of difficulty functioning,” said Hiral Master, PT, MPH, a PhD candidate at the University of Delaware.

The researchers used data from the Osteoarthritis Initia-tive and included participants who had not had TKA at or before a 48-month follow-up visit. They defined walking intensity by step cadence as measured by an accelerometer:

• Fewer than one step per minute was defined as non-walking.

• 1-49 steps per minute was defined as very light walking.

• 50-100 steps per minute was defined as light walking.

• More than 100 steps per minute was defined as moder-ate to vigorous walking.

The study measured the months between the baseline visit and the date of surgery (if within 5 years) or the 108-month visit. Participants who did not receive TKA at the 108-month visit or who were lost to follow-up were removed from analyses. The study included 1,854 partici-pants who had not received TKA; the mean age was 65 years, their mean body mass index was 28.4 kg/m2, and 55% were female. Participants wore their accelerometers for at least 4 of 7 days.

Over the course of 5 years, 108 participants under-went TKA. Participants who had replaced 5 minutes per day of non-walking time with 5 minutes per day of walking at a moderate to vigorous intensity reduced their risk of TKA by 16 percent, the authors said. Walking at a very light or light intensity had no effect. The research-ers found similar results when they analyzed samples of patients with radiographic and symptomatic knee OA.

Based on the findings, the authors urged clinicians to encourage their patients with knee OA or at high risk for the condition to walk briskly 5 to 10 continuous minutes every day. ●

“Walking may exacerbate knee pain and further make things worse, but on the other hand, walking is helpful to build and maintain strength and may prevent the development of difficulty functioning,”

—Geoffrey Tison, MD, MPH

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