Rheumatology Current Awareness Newsletter

June 2016

Outreach Your Outreach Librarian can help facilitate evidence-based practise for

all Rheumatology staff, as well as assisting with academic study and research. We can help with literature searching, obtaining journal

articles and books, and setting up individual current awareness alerts.

Literature Searching We provide a literature searching service for any library member. For those embarking on their own research it is advisable to book some

time with one of the librarians for a 1 to 1 session where we can guide you through the process of creating a well-focused literature research and introduce you to the health databases access via NHS Evidence.

Critical Appraisal Training We also offer one-to-one or small group training in literature

searching, accessing electronic journals, and critical appraisal/Statistics. These are essential courses that teach how to

interpret clinical papers.

For more information, email: katie.barnard@uhbristol.nhs.uk

Books Books can be searched for using SWIMS our online catalogue at

www.swims.nhs.uk. Books and journals that are not available on site or electronically may be requested from other locations. Please email

requests to: library@uhbristol.nhs.uk

Contents

1: Tables of Contents from June’s

Rheumatology journals

2: New NICE Guidance

3: Latest relevant Systematic Reviews from

the Cochrane Library

4: New activity in Uptodate

5: Quick Exercise

6: Current Awareness database articles

Tables of Contents from Rheumatology journals

The links below will take you to the full Tables of Contents.

If you require full articles please email: library@uhbristol.nhs.uk

Rheumatology June 2016, Volume 55, Issue 6

Annals of Rheumatic Disease June 2016, Volume 75, Issue 6

Arthritis & Rheumatology June 2016, Volume 68, Issue 6

Journal of Rheumatology June 2016 Volume 43 Issue 6 Osteoporosis International June 2016 Volume 27 Issue 6

New NICE Guidance

IPG558 Biodegradable subacromial spacer insertion for rotator cuff tears

Latest relevant Systematic Reviews from the

Cochrane Library

Professional interventions for general practitioners on the management of musculoskeletal conditions

Biologics or tofacitinib for rheumatoid arthritis in incomplete responders to methotrexate or other traditional disease‐modifying anti‐rheumatic drugs: a systematic review and network meta‐analysis

New activity in Uptodate

www.uptodate.com

You will need your NHS Athens username/password (register through http://openathens.nice.org.uk/)

Acetaminophen for knee and hip osteoarthritis (May 2016)

Treatment with acetaminophen (paracetamol, N-acetyl-p-aminophenol [APAP]) appears to be slightly

more effective than no treatment in relieving overall pain from osteoarthritis (OA), but generally less

effective than nonsteroidal antiinflammatory drugs (NSAIDs). This was recently illustrated in a 2016

network meta-analysis of randomized trials involving nearly 60,000 patients with knee or hip OA

receiving either APAP, one of seven NSAIDs, or placebo [6]. The summary estimates of benefit with

APAP were extremely low, although statistically significant, for the highest dose of APAP, but

less than the predefined minimum clinically important effect. These results do not exclude the

possibility that some patients respond, while many others do not. In patients with OA lacking signs or

symptoms of inflammation, we initiate pharmacologic therapy with acetaminophen on an as-needed

basis. If this is inadequate, we advise a trial of acetaminophen on a scheduled basis up to three to

four times daily. Such use is consistent with evidence supporting its modest benefit compared with

placebo and its relative safety. (See "Initial pharmacologic therapy of osteoarthritis", section on

'Noninflammatory OA'.)

Tocilizumab for systemic sclerosis (May 2016)

New strategies under investigation for the treatment of systemic sclerosis (SSc, scleroderma) include

the anti-interleukin (IL)-6 receptor antibody, tocilizumab, based upon the association of high IL-6

expression with disease severity and poor outcome, evidence of a role for IL-6 in the

microvasculopathy in SSc, and case reports suggesting potential benefit from the drug. In a

recent phase 2 randomized trial involving nearly 90 patients with SSc for five years or less, patients

receiving tocilizumab failed to achieve a statistically significant reduction in the modified Rodnan skin

score (mRSS) at weeks 24 and 48, compared with those receiving placebo, although scores did

improve and several secondary endpoints favored tocilizumab [12]. A larger, phase 3 trial is ongoing

to further evaluate the potential role of such therapy in practice. (See "Immunomodulatory and

antifibrotic approaches to the treatment of systemic sclerosis (scleroderma)", section on 'Other

biologic agents'.)

Macitentan ineffective for ischemic digital ulcers in systemic sclerosis (May 2016)

Inhibition of vasoconstrictor endothelin-1 (ET-1) by the drug bosentan was previously shown to

reduce the frequency of recurrent digital ulcers associated with systemic sclerosis (SSc, scleroderma)

and to improve pulmonary hypertension (PH). Despite this, another potent nonselective ET-1

antagonist, macitentan, did not reduce the frequency of new ischemic digital ulcers over 16 weeks,

compared with placebo, in two randomized trials involving a total of over 550 patients with SSc,

although the number of new ulcers was lower than expected among the participants in both

trials [13]. However, macitentan has been shown to be beneficial in PH. The basis for the differences

between these two ET-1 inhibitors is unknown. (See "Treatment of the Raynaud phenomenon

resistant to initial therapy", section on 'Recurrent digital ulcers in scleroderma'.)

Upcoming Lunchtime Drop-in Sessions

July (1pm)

Tue 5th Critical Appraisal

Wed 13th Statistics

Thurs 21st Information resources

Fri 29th Literature Searching

June (12pm)

Weds 8th Understanding articles

Thurs 16th Statistics

Fri 24th Information resources

The Library and Information Service provides free specialist information skills training for

all UHBristol staff and students. To book a place, email: library@uhbristol.nhs.uk

If you’re unable to attend we also provide one-to-one or small group sessions. Contact

library@uhbristol.nhs.uk or katie.barnard@uhbristol.nhs.uk to arrange a session.

Quick Exercise

Relative Risk The relative risk is the ratio of probability of an event (a specified outcome) occurring in one group (i.e. those exposed to a particular intervention) compared to those in another group (i.e. those not exposed – a control group). The relative risk can be interpreted using the following chart. First, you must determine whether the event (the outcome measure) is adverse or beneficial.

Relative Risk Adverse outcome (e.g. death) Beneficial outcome (e.g. recovery of limb function)

<1 Intervention better than control

Intervention worse than control

1 Intervention no better or worse than control

Intervention no better or worse than control

>1 Intervention worse than control

Intervention better than control

Have a go at interpreting the relative risks for these three studies using the chart above. Is the intervention better or worse than the control?

Intervention Population Outcome measure (think: adverse or beneficial?)

Relative Risk

Study 1 Drug X Adults at risk of a heart attack

Heart attack 1.2

Study 2 Therapy programme Y

Smokers Smoking cessation 0.8

Study 3 Probiotic Z Children on antibiotics Diarrhoea 0.3

Find out more about relative risk in one of our Basic Statistics training sessions.

For more details, email library@uhbristol.nhs.uk.

Current Awareness database articles

If you require full articles please email: library@uhbristol.nhs.uk

Title: Tocilizumab for induction and maintenance of remission in giant cell arteritis: a phase 2, randomised, double-blind, placebo-controlled trial. Citation: Lancet (London, England), May 2016, vol. 387, no. 10031, p. 1921-1927, 1474-547X Author(s): Villiger, Peter M, Adler, Sabine, Kuchen, Stefan, Wermelinger, Felix, Dan, Diana, Fiege, Veronika, Bütikofer, Lukas, Seitz, Michael, Reichenbach, Stephan Abstract: Giant cell arteritis is an immune-mediated disease of medium and large-sized arteries that affects mostly people older than 50 years of age. Treatment with glucocorticoids is the gold-standard and prevents severe vascular complications but is associated with substantial morbidity and mortality. Tocilizumab, a humanised monoclonal antibody against the interleukin-6 receptor, has been associated with rapid induction and maintenance of remission in patients with giant cell arteritis. We therefore aimed to study the efficacy and safety of tocilizumab in the first randomised clinical trial in patients with newly diagnosed or recurrent giant cell arteritis. In this single centre, phase 2, randomised, double-blind, placebo-controlled trial, we recruited patients aged 50 years and older from University Hospital Bern, Switzerland, who met the 1990 American College of Rheumatology criteria for giant cell arteritis. Patients with new-onset or relapsing disease were randomly assigned (2:1) to receive either tocilizumab (8 mg/kg) or placebo intravenously. 13 infusions were given in 4 week intervals until week 52. Both groups received oral prednisolone, starting at 1 mg/kg per day and tapered down to 0 mg according to a standard reduction scheme defined in the study protocol. […] Our findings show, for the first time in a trial setting, the efficacy of tocilizumab in the induction and maintenance of remission in patients with giant cell arteritis.

Title: Economic Burden of Switching to a Non-Tumor Necrosis Factor Inhibitor Versus a Tumor Necrosis Factor Inhibitor Biologic Therapy among Patients with Rheumatoid Arthritis. Citation: Advances in therapy, May 2016, vol. 33, no. 5, p. 807-823, 1865-8652 (May 2016) Author(s): Zhou, Zheng-Yi, Griffith, Jenny, Du, Ella Xiaoyan, Chin, Daniel, Betts, Keith A, Ganguli, Arijit Abstract: The objective of this study was to examine healthcare resource utilization (HRU) and costs associated with switching to another tumor necrosis factor alpha inhibitor (TNFi) therapy versus a non-TNFi therapy among patients with rheumatoid arthritis (RA) discontinuing use of an initial TNFi biologic therapy. Patients with ≥2 RA diagnoses who used ≥1 TNFi on or after their initial RA diagnosis were identified in a US employer-based insurance claims database. Patients were selected based on ≥1 claim of another TNFi or a non-TNFi biologic therapy (occurring after 2010, and within 30 days before to 60 days after discontinuation of the initial TNFi), and continuous insurance ≥6 months before (baseline period) and ≥12 months after the switch date (study period). Patient demographic and clinical characteristics were measured during the baseline period. All-cause and RA-related HRU and costs were analyzed during the 12-month study period using multivariable regression analysis controlling for baseline characteristics and selected comorbidities. […] Adult patients with RA discontinuing TNFi therapy who switched to an alternative TNFi incurred lower healthcare costs than patients who switched to a non-TNFi biologic. AbbVie, Inc.

Title: The term 'non-radiographic axial spondyloarthritis' is much more important to classify than to diagnose patients with axial spondyloarthritis. Citation: Annals of the rheumatic diseases, May 2016, vol. 75, no. 5, p. 791-794 Author(s): Deodhar, Atul, Strand, Vibeke, Kay, Jonathan, Braun, Juergen Abstract: The term axial spondyloarthritis (axSpA) now is used frequently to describe patients with predominantly axial symptoms who fit into the spectrum of a well-recognised rheumatic disease that continues to be known as ankylosing spondylitis (AS). The 2009 Assessment of SpondyloArthritis international Society (ASAS) classification criteria, developed to identify patients with early or atypical disease which could not be classified by the 1984 modified New York (mNY) criteria for AS, have led to a differentiation between non-radiographic axial spondyloarthritis (nr-axSpA) and radiographic axSpA, which is largely synonymous with AS. The main reason to distinguish between these ends of the spectrum of axSpA was that tumor necrosis factor (TNF) inhibitors (TNFi) approved for AS could obtain additional labelling for nr-axSpA and be used to treat all patients manifesting clinical features of axSpA. These two terms are distinguished by the degree of 'radiographic sacroiliitis' assessed by conventional radiography, according to the 1984 mNY criteria for AS. Since this differentiation has been shown to be not very reliable, we argue that the terms nr-axSpA and AS should only be used for classification of patients with axSpA and not as separate diagnoses. Therefore, we propose that only the term axSpA be used to diagnose patients, unless there is a meaningful medical reason to differentiate nr-axSpA from AS. The available data justify performing randomised controlled trials designed to obtain regulatory approval for therapeutic agents in patients across the entire spectrum of axSpA. Full Text: Available from Highwire Press in EULAR Meeting Abstracts Available from Highwire Press in Annals of the Rheumatic Diseases

Title: Effectiveness of Foot Orthoses Versus Rocker-Sole Footwear for First Metatarsophalangeal Joint Osteoarthritis: Randomized Trial. Citation: Arthritis care & research, May 2016, vol. 68, no. 5, p. 581-589, 2151-4658 (May 2016) Author(s): Menz, Hylton B, Auhl, Maria, Tan, Jade M, Levinger, Pazit, Roddy, Edward, Munteanu, Shannon E Abstract: To compare the effectiveness of prefabricated foot orthoses to rocker-sole footwear in reducing foot pain in people with first metatarsophalangeal (MTP) joint osteoarthritis (OA). Participants (n = 102) with first MTP joint OA were randomly allocated to receive individualized, prefabricated foot orthoses or rocker-sole footwear. The primary outcome measure was the pain subscale on the Foot Health Status Questionnaire (FHSQ) at 12 weeks. Secondary outcome measures included the function, footwear, and general foot health subscales of the FHSQ; the Foot Function Index; severity of pain and stiffness at the first MTP joint; perception of global improvement; general health status; use of rescue medication and co-interventions to relieve pain; physical activity; and the frequency of self-reported adverse events. The FHSQ pain subscale scores improved in both groups, but no statistically significant difference between the groups was observed (adjusted mean difference 2.05 points, 95% confidence interval [95% CI] -3.61, 7.71; P = 0.477). However, the

footwear group exhibited lower adherence (mean ± SD total hours worn 287 ± 193 versus 448 ± 234; P < 0.001), were less likely to report global improvement in symptoms (39% versus 62%; relative risk [RR] 0.63, 95% CI 0.41, 0.99; P = 0.043), and were more likely to experience adverse events (39% versus 16%; RR 2.47, 95% CI 1.12, 5.44; P = 0.024) compared to the orthoses group. Prefabricated foot orthoses and rocker-sole footwear are similarly effective at reducing foot pain in people with first MTP joint OA. However, prefabricated foot orthoses may be the intervention of choice due to greater adherence and fewer associated adverse events.

Title: Physical Therapist-Delivered Pain Coping Skills Training and Exercise for Knee Osteoarthritis: Randomized Controlled Trial. Citation: Arthritis care & research, May 2016, vol. 68, no. 5, p. 590-602, 2151-4658 (May 2016) Author(s): Bennell, Kim L, Ahamed, Yasmin, Jull, Gwendolen, Bryant, Christina, Hunt, Michael A, Forbes, Andrew B, Kasza, Jessica, Akram, Muhammed, Metcalf, Ben, Harris, Anthony, Egerton, Thorlene, Kenardy, Justin A, Nicholas, Michael K, Keefe, Francis J Abstract: To investigate whether a 12-week physical therapist-delivered combined pain coping skills training (PCST) and exercise (PCST/exercise) is more efficacious and cost effective than either treatment alone for knee osteoarthritis (OA). This was an assessor-blinded, 3-arm randomized controlled trial in 222 people (73 PCST/exercise, 75 exercise, and 74 PCST) ages ≥50 years with knee OA. All participants received 10 treatments over 12 weeks plus a home program. PCST covered pain education and training in cognitive and behavioral pain coping skills, exercise comprised strengthening exercises, and PCST/exercise integrated both. Primary outcomes were self-reported average knee pain (visual analog scale, range 0-100 mm) and physical function (Western Ontario and McMaster Universities Osteoarthritis Index, range 0-68) at week 12. Secondary outcomes included other pain measures, global change, physical performance, psychological health, physical activity, quality of life, and cost effectiveness. Analyses were by intent-to-treat methodology with multiple imputation for missing data. A total of 201 participants (91%), 181 participants (82%), and 186 participants (84%) completed week 12, 32, and 52 measurements, respectively. At week 12, there were no significant between-group differences for reductions in pain comparing PCST/exercise versus exercise (mean difference 5.8 mm [95% confidence interval (95% CI) -1.4, 13.0]) and PCST/exercise versus PCST (6.7 mm [95% CI -0.6, 14.1]). Significantly greater improvements in function were found for PCST/exercise versus exercise (3.7 units [95% CI 0.4, 7.0]) and PCST/exercise versus PCST (7.9 units [95% CI 4.7, 11.2]). These differences persisted at weeks 32 (both) and 52 (PCST). Benefits favoring PCST/exercise were seen on several secondary outcomes. Cost effectiveness of PCST/exercise was not demonstrated. This model of care could improve access to psychological treatment and augment patient outcomes from exercise in knee OA, although it did not appear to be cost effective.

Title: Efficacy, Tolerability, and Safety of Cannabinoid Treatments in the Rheumatic Diseases: A Systematic Review of Randomized Controlled Trials. Citation: Arthritis care & research, May 2016, vol. 68, no. 5, p. 681-688, 2151-4658 (May 2016) Author(s): Fitzcharles, Mary-Ann, Ste-Marie, Peter A, Häuser, Winfried, Clauw, Daniel J, Jamal, Shahin, Karsh, Jacob, Landry, Tara, Leclercq, Sharon, Mcdougall, Jason J, Shir, Yoram, Shojania, Kam, Walsh, Zach

Abstract: To assess the efficacy, tolerability, and safety of cannabinoids (phyto- and syntheto-) in the management of rheumatic diseases. Multiple databases, including Medline, Embase, and CENTRAL, were searched. Randomized controlled trials with outcomes of pain, sleep, quality of life, tolerability (dropouts due to adverse events), and safety (serious adverse events), with comparison of cannabinoids with any type of control, were included. Study methodology quality was evaluated with the Cochrane risk of bias tool. In 4 short-term studies comprising 203 patients (58 with rheumatoid arthritis, 71 with fibromyalgia, and 74 with osteoarthritis [OA]), cannabinoids had a statistically significant effect on pain in 2, sleep in 2, and improved quality of life in 1, with the OA study prematurely terminated due to futility. The risk of bias was high for all 3 completed studies. Dizziness, cognitive problems, and drowsiness, as well as nausea, were reported for almost half of the patients. No serious adverse events were reported for cannabinoids during the study duration. No studies of herbal cannabis were identified. Extremely small sample sizes, short study duration, heterogeneity of rheumatic conditions and products, and absence of studies of herbal cannabis allow for only limited conclusions for the effects of cannabinoids in rheumatic conditions. Pain relief and effect on sleep may have some potential therapeutic benefit, but with considerable mild to moderate adverse events. There is currently insufficient evidence to recommend cannabinoid treatments for management of rheumatic diseases pending further study.

Title: Spironolactone for People Age 70 Years and Older With Osteoarthritic Knee Pain: A Proof-of-Concept Trial. Citation: Arthritis care & research, May 2016, vol. 68, no. 5, p. 716-721, 2151-4658 (May 2016) Author(s): Mcmurdo, Marion E T, Sumukadas, Deepa, Donnan, Peter T, Cvoro, Vera, Rauchhaus, Petra, Argo, Ishbel, Waldie, Helen, Littleford, Roberta, Struthers, Allan D, Witham, Miles D Abstract: To determine whether spironolactone could benefit older people with osteoarthritis (OA), based on a previous study showing that spironolactone improved quality of life. This parallel-group, randomized, placebo-controlled, double-blind trial randomized community-dwelling people ages ≥70 years with symptomatic knee OA to 12 weeks of 25 mg daily oral spironolactone or matching placebo. The primary outcome was between-group difference in change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale scores. Secondary outcomes included WOMAC stiffness and physical function subscores, EuroQol 5-domain (EQ-5D) 3L score, and mechanistic markers. Analysis was by intent to treat, using mixed-model regression, adjusting for baseline values of test variables. A total of 421 people had eligibility assessed, and 86 were randomized. Mean ± SD age was 77 ± 5 years and 53 of 86 (62%) were women. Adherence to study medication was 99%, and all participants completed the 12-week assessment. No significant improvement was seen in the WOMAC pain score (adjusted treatment effect 0.5 points [95% confidence interval (95% CI) - 0.3, 1.3]; P = 0.19). No improvement was seen in WOMAC stiffness score (0.2 points [95% CI -0.6, 1.1]; P = 0.58), WOMAC physical function score (0.0 points [95% CI -0.7, 0.8]; P = 0.98), or EQ-5D 3L score (0.04 points [95% CI -0.04, 0.12]; P = 0.34). Cortisol, matrix metalloproteinase 3, and urinary C-telopeptide of type II collagen were not significantly different between groups. More minor adverse events were noted in the spironolactone group (47 versus 32), but no increase in death or hospitalization was evident. Spironolactone did not improve symptoms, physical function, or health-related quality of life in older people with knee OA.

Title: No predictive effect of body mass index on clinical response in patients with rheumatoid arthritis after 24 weeks of biological disease-modifying antirheumatic drugs: a single-center study.

Citation: Clinical rheumatology, May 2016, vol. 35, no. 5, p. 1129-1136, 1434-9949 (May 2016) Author(s): Kim, Seong-Kyu, Choe, Jung-Yoon, Park, Sung-Hoon, Lee, Hwajeong Abstract: The aim of this study was to determine whether body mass index (BMI) is associated with clinical response to biologics in patients with rheumatoid arthritis (RA). We enrolled 68 patients with RA who were treated with biological disease-modifying antirheumatic drugs (bDMARDs). Biologics included abatacept, tocilizumab, and tumor necrosis factor-α (TNF-α) blockers (etanercept and adalimumab). Baseline BMI (kg/m(2)) was classified as normal (BMI < 23.0), overweight (23.0 ≤ BMI < 25.0), or obese (BMI ≥ 25.0). Improvement of disease activity score 28 (DAS28) and achievement of the European League Against Rheumatism (EULAR) remission and responses between baseline and 24 weeks were our measures of clinical improvement. Mean baseline BMI before treatment with bDMARDs in patients with RA was 22.2 (SD 3.6). DAS28-ESR and DAS28-CRP were significantly reduced from baseline after 24 weeks of treatment with bDMARDs (p < 0.001 of both). ∆DAS28-ESR and ∆DAS28-CRP were not found among patients with normal, overweight, or obese BMI (p = 0.133 and p = 0.255, respectively) nor were EULAR responses or EULAR remission (p = 0.540 and p = 0.957, respectively). Logistic regression analysis showed no relationship of BMI with EULAR clinical responses (p = 0.093 for good response and p = 0.878 for EULAR remission). This study reveals that BMI is not a predictive factor of clinical response to bDMARDs in patients with RA.

Title: Resource utilisation and direct costs in patients with recently diagnosed fibromyalgia who are offered one of three different interventions in a randomised pragmatic trial. Citation: Clinical rheumatology, May 2016, vol. 35, no. 5, p. 1307-1315, 1434-9949 (May 2016) Author(s): van Eijk-Hustings, Yvonne, Kroese, Mariëlle, Creemers, An, Landewé, Robert, Boonen, Annelies Abstract: The purpose of this study is to understand the course of costs over a 2-year period in a cohort of recently diagnosed fibromyalgia (FM) patients receiving different treatment strategies. Following the diagnosis, patients were randomly assigned to a multidisciplinary programme (MD), aerobic exercise (AE) or usual care (UC) without being aware of alternative interventions. Time between diagnosis and start of treatment varied between patients. Resource utilisation, health care costs and costs for patients and families were collected through cost diaries. Mixed linear model analyses (MLM) examined the course of costs over time. Linear regression was used to explore predictors of health care costs in the post-intervention period. Two hundred three participants, 90 % women, mean (SD) age 41.7 (9.8) years, were included in the cohort. Intervention costs per patient varied from €864 to 1392 for MD and were €121 for AE. Health care costs (excluding intervention costs) decreased after diagnosis, but before the intervention in each group, and increased again afterwards to the level close to the diagnostic phase. In contrast, patient and family costs slightly increased over time in all groups without initial decrease immediately after diagnosis. Annualised health care costs post-intervention varied between €1872 and 2310 per patient and were predicted by worse functioning and high health care costs at diagnosis. In patients with FM, health care costs decreased following the diagnosis by a rheumatologist. Offering patients a specific intervention after diagnosis incurred substantial costs while having only marginal effects on costs.

Title: Effects of music on pain in patients with fibromyalgia. Citation: Clinical rheumatology, May 2016, vol. 35, no. 5, p. 1317-1321, 1434-9949 (May 2016)

Author(s): Alparslan, Güler Balcı, Babadağ, Burcu, Özkaraman, Ayşe, Yıldız, Pınar, Musmul, Ahmet, Korkmaz, Cengiz Abstract: Fibromyalgia syndrome (FMS) is a chronic syndrome characterized by diffuse musculoskeletal system pain and painful tender points in certain areas of the body. The aim of the investigation was to determine the effects of music on pain in fibromyalgia patients. This randomized clinical trial was carried out with 37 fibromyalgia outpatients as an experimental group (n = 21) and control group (n = 16) at a University Hospital Internal Medicine and Rheumatology Clinic between 1 June and 1 December 2014. The research instruments used were descriptive characteristics questionnaire, Visual Analogue Scale (VAS), music CD which includes water and wave sounds recommended by the Turkish Psychological Association for psychological relaxation, and pain evaluation form. According to the findings, the average age of patients was 43.59 years ± 10.30, 94.6 % were women and 81.1 % were married. The fibromyalgia patients had the disease ranged from 1 month to 20 years, the average of disease duration was 23.6 ± 45.5 months, and the average of pain intensity was 6.89 ± 1.64 on the VAS. Average pain was reported in the experimental group in VAS on day 1 (5.45 ± 2.73), day 7 (4.57 ± 2.71), and day 14 (4.14 ± 2.45), and significant reduction in pain in the listening music group was seen (p = 0.026). A repeated measure analysis of variance controlling for differences between days demonstrated a significant decrease in pain between day 1 and day 14 (p = 0.022). There was no significant decrease in pain among control group participants. The effect of music has been found to control pain in fibromyalgia patients. Music therapy should be suggested in pain management for fibromyalgia patients as an non-pharmacologic nursing intervention.

Title: Economic Burden and Treatment Patterns of Cycling between Conventional Synthetic Disease-modifying Antirheumatic Drugs Among Biologic-treated Patients with Rheumatoid Arthritis. Citation: Clinical therapeutics, May 2016, vol. 38, no. 5, p. 1205-1216, 1879-114X (May 2016) Author(s): Betts, Keith A, Griffith, Jenny, Ganguli, Arijit, Li, Nanxin, Douglas, Kevin, Wu, Eric Q Abstract: To assess the economic outcomes and treatment patterns among patients with rheumatoid arthritis (RA) who used 1, 2, or 3 or more conventional synthetic disease-modifying antirheumatic drugs (DMARDs) before receiving a biologic therapy. Adult patients with ≥2 RA diagnoses (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes 714.xx) on different dates, ≥1 claim for a conventional synthetic DMARD, and ≥1 claim for a biologic DMARD were identified from a large commercial claims database. The initiation date of the first biologic DMARD was defined as the index date. Based on the number of distinct conventional synthetic DMARDs initiated between the first RA diagnosis and the index date, patients were classified into 3 cohorts: those who used 1, 2, or 3 or more conventional synthetic DMARDs. Baseline characteristics were measured 6 months preindex date and compared between the 3 cohorts. All-cause health care costs (in 2014 US$) were compared during the follow-up period (12 months postbiologic initiation) using multivariable gamma models adjusting for baseline characteristics. Time to discontinuation of the index biologic DMARD and time to switching to a new DMARD were compared using multivariable Cox proportional hazards models. The 1, 2, and 3 or more conventional synthetic DMARD cohorts included 6215; 3227; and 976 patients, respectively. At baseline, patients in the 3 or more conventional synthetic DMARD cohort had the least severe RA, as indicated by the lowest claims-based index for RA severity score (1 vs 2 vs 3 or more = 6.1 vs 5.9 vs 5.8). During the study period, there was a significant association between number of conventional synthetic DMARDs and higher all-cause total health care costs (adjusted mean difference, 1 vs 2:

$772; P < 0.001; 2 vs 3 or more: $2390; P < 0.001). The all-cause medical and pharmacy costs were also significantly higher with the increasing number of conventional synthetic DMARDs. Patients who cycled more conventional synthetic DMARDs were also more likely to switch treatment after biologic initiation (1 vs 2: adjusted hazard ratio = 0.89; P = 0.005; 2 vs 3 or more: adjusted hazard ratio = 0.89; P = 0.087). There were no differences in index biologic discontinuation between the 3 cohorts. Patients with RA who cycled more conventional synthetic DMARDs had increased economic burden in the 12 months following biologic initiation and were more likely to switch therapy. These results highlight the importance of timely switching to biologic DMARDs for the treatment of RA.

Title: Retinal vasculitis. Citation: Current opinion in rheumatology, May 2016, vol. 28, no. 3, p. 228-235 Author(s): Rosenbaum, James T, Sibley, Cailin H, Lin, Phoebe Abstract: Ophthalmologists and rheumatologists frequently have a miscommunication among themselves, and as a result differ in their opinion for patients consulting them with retinal vasculitis. This report seeks to establish a common understanding of the term, retinal vasculitis, and to review recent studies on this diagnosis. The genetic basis of some rare forms of retinal vascular disease has recently been described. Identified genes include CAPN5, TREX1, and TNFAIP3; Behçet's disease is a systemic illness that is very commonly associated with occlusive retinal vasculitis; retinal imaging, including fluorescein angiography and other newer imaging modalities, has proven crucial to the identification and characterization of retinal vasculitis and its complications; although monoclonal antibodies to interleukin-17A or interleukin-1 beta failed in trials for Behçet's disease, antibodies to TNF-alpha, either infliximab or adalimumab, have demonstrated consistent benefit in managing this disease. Interferon treatment and B-cell depletion therapy via rituximab may be beneficial in certain types of retinal vasculitis. Retinal vasculitis is an important entity for rheumatologists to understand. Retinal vasculitis associated with Behçet's disease responds to monoclonal antibodies that neutralize TNF, but the many other forms of noninfectious retinal vasculitis may require alternate therapeutic management.

Title: Management of connective tissue diseases associated interstitial lung disease: a review of the published literature. Citation: Current opinion in rheumatology, May 2016, vol. 28, no. 3, p. 236-245 Author(s): Wallace, Beth, Vummidi, Dharshan, Khanna, Dinesh Abstract: Interstitial lung disease (ILD), though a common and often a severe manifestation of many connective tissue diseases (CTD), is challenging to manage because of its variable presentation and the relative lack of guidelines to assist the clinician. In this review, we discuss the approach to diagnosis, treatment, and monitoring patients with CTD-associated ILD, with a focus on systemic sclerosis (SSc), rheumatoid arthritis (RA), and idiopathic inflammatory myopathy (IIM). High-resolution computed tomography scan and pulmonary function testing can be reliably used to diagnose ILD and monitor progression, and often to determine its likely histologic subtype and severity. In SSc-ILD, randomized controlled trials show ILD stabilization with cyclophosphamide treatment; preliminary data from another randomized controlled trial demonstrates similar findings with mycophenolate. There are no robust clinical trials supporting specific treatments for RA-ILD or IIM-ILD, but rituximab in RA-ILD, and cyclophosphamide, mycophenolate and calcineurin inhibitors in

IIM-ILD show promise. Though ILD contributes substantially to morbidity and mortality in patients with CTD, there are minimal data to guide its management except in SSc-ILD.

Title: New concepts of clinical trials in rheumatoid arthritis: a boom of noninferiority trials. Citation: Current opinion in rheumatology, May 2016, vol. 28, no. 3, p. 316-322 Author(s): Landewé, Robert, van der Heijde, Désirée Abstract: The purpose is to describe the most recent randomized controlled trials (RCT) in patients with rheumatoid arthritis that had a noninferiority design, and to focus on methodological aspects of noninferiority. In 2014 and 2015 10 different RCTs with a noninferiority-design could be identified, in comparison to only a few in the decade before. Most RCTs had a rather small sample size, and had ill-defined noninferiority-margins, or noninferiority-margins without comprehensible clinical meaning. Six of the 10 trials indeed arrived at a conclusion of 'noninferiority'; four did not. Interestingly, many of the RCTs were pragmatic studies comparing strategies, and the investigators were neither blind to the treatment nor to the outcome. In addition, the treatments were often adaptive (e.g. treat-to-target approach). These characteristics are considered built-in incentives for noninferiority. In the competitive pharmaceutical landscape of rheumatoid arthritis, with many effective drugs and strategies, it is no surprise that the number of noninferiority-trial (sharply) rises. But noninferiority trials are difficult to design, conduct, and interpret, and many principles of noninferiority-trial designs are currently ignored, which may jeopardise their conclusions to some extent.

Title: Treat-to-target in systemic lupus erythematosus: are we there yet? Citation: Expert review of clinical pharmacology, May 2016, vol. 9, no. 5, p. 675-680 Author(s): Mok, Chi Chiu Abstract: The treat-to-target (T2T) strategy has proven benefits in several chronic medical illnesses including rheumatoid arthritis. Whether the T2T principle can be applied to SLE has become a recent topic of discussion. A European panel of rheumatologists agrees that treatment of SLE should target at multiple goals that include control of disease activity, prevention of disease flares, minimization of disease or treatment related comorbidity, and improvement of quality of life. Therapy of SLE should aim at remission or when remission cannot be achieved, the lowest possible disease activity that is assessed by a validated lupus activity index and/or organ-specific markers. However, owing to the clinical heterogeneity of SLE, there is still no consensus on the definition of remission or low disease activity state in individual organ-systems. In real life, agents readily available for therapy switching in SLE are limited. Moreover, no disease activity index is universally agreed upon for disease monitoring to make therapeutic decisions. Currently, clinical parameters for the assessment and monitoring of lupus renal disease appear to be more objective and evidence-based. A therapeutic target in terms of proteinuria and/or other renal parameters should be tested in randomized controlled trials for the proof of the T2T concept in SLE.

Title: Relationship Between RANK and RANKL Gene Polymorphisms with Osteoporosis in Rheumatoid Arthritis Patients.

Citation: Genetic testing and molecular biomarkers, May 2016, vol. 20, no. 5, p. 249-254 Author(s): Mohamed, Randa H, Mohamed, Rasha H, El-Shahawy, Eman E Abstract: Bone disease in rheumatoid arthritis (RA) is a complex phenomenon where genetic risk factors have been partially evaluated. In the present study, we aimed to evaluate the relationship between polymorphisms of the receptor activator of the nuclear factor kappa B (RANK) gene; the receptor activator of the nuclear factor kappa B ligand (RANKL) gene; and RANKL levels with osteoporosis in postmenopausal RA patients. One hundred seventy-two postmenopausal female patients and 176 age- and sex-matched controls were enrolled in the study. All subjects were genotyped for the presence of RANK C575T (rs1805034) and RANKL C290T (rs9525641) gene polymorphisms. RANKL levels, bone mineral density (BMD), and biochemical markers were also obtained. Women with the RANK CC genotype were significantly (2X) more likely to develop osteoporosis than those with the TT genotype (p = 0.024). A significant association was also observed between the RANKL 290TT genotype and both BMD and RANKL levels. In addition, individuals with the -290TT genotype were twice as likely to develop osteoporosis as those with the CC genotype (p < 0.001). Postmenopausal women with RA, carrying either the RANKL-290T allele or possessing the RANK 575CC genotype were more likely to develop osteoporosis. Moreover, our results suggested that the polymorphism 290C>T could be considered a risk factor for genetic susceptibility to osteoporosis and low BMD.

Title: Reactivation of hepatitis B virus in rheumatoid arthritis patients treated with biological disease-modifying antirheumatic drugs. Citation: International journal of rheumatic diseases, May 2016, vol. 19, no. 5, p. 470-475 Author(s): Nakamura, Jun, Nagashima, Takao, Nagatani, Katsuya, Yoshio, Taku, Iwamoto, Masahiro, Minota, Seiji Abstract: To examine the incidence of hepatitis B virus (HBV) reactivation in patients with rheumatoid arthritis (RA) receiving biological disease-modifying antirheumatic drugs (DMARDs). We retrospectively reviewed RA patients treated with biological DMARDs at our institution from July 2010 to December 2012. Patients with antibodies for hepatitis B core antigen and/or hepatitis B surface antigen were regarded as having prior HBV infection. Clinical data on these patients, including HBV-DNA levels, were retrieved from the medical records. During the study period, 251 patients were administered various biological DMARDs. Six patients with a history of HBV vaccination and one patient with positive HBV surface antigen were excluded from the study. Fifty-seven of the remaining 244 patients (23.4%) had prior HBV infection. These patients were followed for a median of 18 months (range: 2-27 months) and HBV-DNA was examined a median of seven times (range: 2-27). HBV-DNA was detected in three patients (5.3%), comprising two receiving tocilizumab and one receiving etanercept. However, HBV-DNA levels were below the quantitation limit (<2.1 log copies mL(-1) ) in all three patients. HBV-DNA became negative again within several months in all three patients, while biological DMARDs were continued and liver function tests remained normal throughout. HBV-DNA reactivation occurred in 5.3% of RA patients with prior HBV infection during treatment with biological DMARDs, but there were no associated clinical manifestations. Accordingly, it seems that biological DMARDs can be used safely in patients with RA.

Title: Reverse shoulder prosthesis in patients with rheumatoid arthritis: a systematic review.

Citation: International orthopaedics, May 2016, vol. 40, no. 5, p. 965-973, 1432-5195 (May 2016) Author(s): Postacchini, Roberto, Carbone, Stefano, Canero, Gianfranco, Ripani, Maurizio, Postacchini, Franco Abstract: To obtain detailed information on the outcomes of patients with rheumatoid arthritis (RA) undergoing reverse shoulder arthroplasty (RSA) METHODS: A literature search was conducted for studies reporting on the use of RSA in RA patients from 1990 to 2014. The inclusion criteria were a report of sufficient information on pre-operative status and surgical outcome allowing evaluation of the therapeutic potential of RSA in RA. The literature search resulted in 586 hits, but only five studies that met the inclusion criteria were assessed. There were 100 shoulders that had been operated on, of which 87 were followed for a mean of 55.4 months, the longest follow-up being 11.9 years Most patients had glenohumeral erosive lesions of Larsen Grade III or IV. The Delta III prosthesis was implanted in most cases and in three studies bone graft was used for severe glenoid lesions. The main outcome measures employed were the Constant score (Cs) and ASES questionnaire. The mean increase in Cs and ASES score after surgery was 42.4 and 54 points, respectively. The mean post-operative forward elevation was 120.6°, the average increment being 51° and the mean increase of abduction was 58.5°. The mean prevalence of scapular notching was 35.4 %. The rate of adverse events was 31 %, but the vast majority were of minor severity. Eight prostheses underwent revision, due to infection in four. RSA implanted in RA patients would appear to give similar results to those obtained in massive cuff tears with or without arthropathy.

Title: Risk of incident chronic obstructive pulmonary disease in patients with rheumatoid arthritis: A systematic review and meta-analysis. Citation: Joint, bone, spine : revue du rhumatisme, May 2016, vol. 83, no. 3, p. 290-294 Author(s): Ungprasert, Patompong, Srivali, Narat, Cheungpasitporn, Wisit, Davis Iii, John M Abstract: To investigate the risk of subsequent development of chronic obstructive pulmonary disease (COPD) in patients with rheumatoid arthritis (RA). We conducted a systematic review and meta-analysis of cohort studies that reported relative risk, hazard ratio or standardized incidence ratio with 95% confidence interval (CI), comparing risk of incident COPD in patients with RA versus non-RA participants. Pooled risk ratio and 95% CI were calculated using a random-effect, generic inverse variance method of DerSimonian and Laird. Four retrospective cohort studies with 32,675 patients with RA and 122,204 controls were included in the data analysis. The pooled risk ratio of incident COPD in patients with RA versus control was 1.99 (95% CI, 1.61-2.45). The statistical heterogeneity was high with an I2 of 81%. Our study demonstrated a statistically significant increased risk of subsequent development of COPD among patients with RA.

Title: Evaluation of the effect of acupuncture on hand pain, functional deficits and health-related quality of life in patients with rheumatoid arthritis-A study protocol for a multicenter, double-blind, randomized clinical trial. Citation: Journal of integrative medicine, May 2016, vol. 14, no. 3, p. 219-227 Author(s): Seca, Susana, Kirch, Sebastian, Cabrita, António S, Greten, Henry J

Abstract: Rheumatoid arthritis (RA) is a systemic inflammatory disease characterized by functional disability and pain. Although acupuncture is widely used, until now Western acupuncture studies on RA have not shown conclusive positive results. Acupuncture is regarded as a reflex therapy that has effects on the human autonomic nervous system. By establishing a traditional Chinese medicine (TCM) diagnosis first, the practitioner is able to choose acupoints according to the state of each individual patient. We are interested if acupuncture, using a classical diagnostic procedure to allocate acupoints to the patient according to the Shang Han Lun theory, can be effective in relieving pain, improving hand function and increasing health-related quality of life in RA.The authors intend to harmonize TCM diagnosis according to clinical and genetic profiles. Patients with the TCM diagnosis of a so-called Turning Point syndrome will be followed up in a randomized, prospective, double-blind, placebo-controlled, multicenter and three-armed parallel-group study with a standardized treatment in order to optimize potential therapeutic effects of acupuncture on pain, strength and muscle function of patients with RA as well as the influence on inflammation and quality of life. The findings of this study will provide important clinical information about the feasibility and efficacy of acupuncture treatment for RA patients. In addition, it will explore the feasibility of further acupuncture research. ClinicalTrials.gov Identifier NCT02553005.

Title: Effects of Probiotic Supplementation on Oxidative Stress Indices in Women with Rheumatoid Arthritis: A Randomized Double-Blind Clinical Trial. Citation: Journal of the American College of Nutrition, May 2016, vol. 35, no. 4, p. 291-299 Author(s): Vaghef-Mehrabany, Elnaz, Homayouni-Rad, Aziz, Alipour, Beitullah, Sharif, Sakineh-Khatoun, Vaghef-Mehrabany, Leila, Alipour-Ajiry, Serour Abstract: Rheumatoid arthritis (RA) is an autoimmune inflammatory disease that causes great pain and disability and increasing oxidative stress in patients. The objective of the present study was to evaluate the effects of probiotics-live microorganisms with many health benefits, including antioxidant properties-on oxidative stress indices of patients with RA. This study is a secondary analysis from a previously published study Methods: In a randomized double-blind placebo-controlled clinical trial, 46 patients with RA were assigned to one of two groups; patients in the probiotic group received a daily capsule containing 10(8) colony forming units (CFUs) of Lactobacillus casei 01 (L. casei 01), while those in the placebo group took identical capsules containing maltodextrin, for 8 weeks. In the baseline and at the end of the study, anxiety, physical activity levels, and dietary intakes were assessed. Anthropometric parameters, serum malondialdehyde (MDA), total antioxidant capacity (TAC), erythrocyte superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activities were measured. There was no significant difference between the two groups for demographic characteristics, anthropometric parameters, physical activity, anxiety levels, or dietary intakes, throughout the course of the study. No significant within- and between-group differences were observed for MDA, TAC, or CAT. SOD activity decreased only in the probiotic group and GPx activity decreased in both study groups (p < 0.05); however, no significant between-group difference was found for these enzymes activities at the end of the study (p > 0.05). No significant effect of L. casei 01 supplementation was observed on the oxidative status of patients with RA, compared to placebo.

Title: Macrophage activation syndrome in the era of biologic therapy. Citation: Nature reviews. Rheumatology, May 2016, vol. 12, no. 5, p. 259-268

Author(s): Grom, Alexei A, Horne, AnnaCarin, De Benedetti, Fabrizio Abstract: Macrophage activation syndrome (MAS) refers to acute overwhelming inflammation caused by a 'cytokine storm'. Although increasingly recognized as a life-threatening complication of various rheumatic diseases, clinically, MAS is strikingly similar to primary and secondary forms of haemophagocytic lymphohistiocytosis (HLH). Not surprisingly, many rheumatologists prefer the term secondary HLH rather than MAS to describe this condition, and efforts to change the nomenclature are in progress. The pathophysiology of MAS remains elusive, but observations in animal models, as well as data on the effects of new anticytokine therapies on rates and clinical presentations of MAS in patients with systemic juvenile idiopathic arthritis (sJIA), provide clues to the understanding of this perplexing clinical phenomenon. In this Review, we explore the latest available evidence and discuss potential diagnostic challenges in the era of increasing use of biologic therapies.

Title: Fracture risk in oral glucocorticoid users: a Bayesian meta-regression leveraging control arms of osteoporosis clinical trials. Citation: Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, May 2016, vol. 27, no. 5, p. 1709-1718, 1433-2965 (May 2016) Author(s): Amiche, M A, Albaum, J M, Tadrous, M, Pechlivanoglou, P, Lévesque, L E, Adachi, J D, Cadarette, S M Abstract: Little data exist on the frequency of fracture among oral glucocorticoid users. We examined the effect of oral glucocorticoids on fracture incidence using data from randomized controlled trials. Patients starting glucocorticoids had a higher probability of fracture and decline in bone mineral density compared to chronic glucocorticoid users. Oral glucocorticoids (GCs) are the leading cause of secondary osteoporosis. However, there have been few studies that quantify the rate of fracture among GC users. We sought to provide a pooled estimate of fracture risk from randomized controlled trials (RCTs) of GC-treated patients. We updated a MEDLINE search published by the American College of Rheumatology through to March 2015 and identified RCTs of osteoporosis therapies that reported fracture and bone mineral density (BMD) among oral GC users. We restricted the analysis to placebo or control arms. RCT arms were stratified by GC exposure at enrolment to GC initiators (≤6 months) and chronic GC users (>6 months). Bayesian meta-regression was used to estimate the annual probability of vertebral fracture (primary), non-vertebral fracture and percentage change in lumbar spine and femoral neck BMD. The annual incidence of vertebral and non-vertebral fracture was 5.1 % (95 % CrI = 2.8-8.2) and 2.5 % (95 % CrI = 1.2--4.2) among GC initiators, and 3.2 % (95 % CrI = 1.8-5.0) and 3.0 % (95 % CrI = 0.8-5.9) among chronic GC users. Our meta-regression identified a non-significant effect of group-level variables (mean age, mean BMD, mean GC daily dose, patients with previous vertebral fractures, proportion of women and adjuvant used) on vertebral fracture rate. Our study found higher vertebral fracture incidence among GC initiators, yet a relative decline in fracture incidence with longer exposure. Our findings suggest that fracture incidence among oral GC users may be more common than previously estimated. Optimizing GC-induced osteoporosis management during early exposure to GC is essential to prevent fractures.

Title: Clinical and regulatory perspectives on biosimilar therapies and intended copies of biologics in rheumatology.

Citation: Rheumatology international, May 2016, vol. 36, no. 5, p. 613-625, 1437-160X (May 2016) Author(s): Mysler, Eduardo, Pineda, Carlos, Horiuchi, Takahiko, Singh, Ena, Mahgoub, Ehab, Coindreau, Javier, Jacobs, Ira Abstract: Biologics are vital to the management of patients with rheumatic and musculoskeletal diseases such as rheumatoid arthritis and other inflammatory and autoimmune conditions. Nevertheless, access to these highly effective treatments remains an unmet medical need for many people around the world. As patents expire for existing licensed biologic (originator) products, biosimilar products can be approved by regulatory authorities and enter clinical use. Biosimilars are highly similar copies of originator biologics approved through defined and stringent regulatory processes after having undergone rigorous analytical, non-clinical, and clinical evaluations. The introduction of high-quality, safe, and effective biosimilars has the potential to expand access to these important medicines. Biosimilars are proven to be similar to the originator biologic in terms of safety and efficacy and to have no clinically meaningful differences. In contrast, "intended copies" are copies of originator biologics that have not undergone rigorous comparative evaluations according to the World Health Organization recommendations, but are being commercialized in some countries. There is a lack of information about the efficacy and safety of intended copies compared with the originator. Furthermore, they may have clinically significant differences in formulation, dosages, efficacy, or safety. In this review, we explore the differences between biosimilars and intended copies and describe key concepts related to biosimilars. Familiarity with these topics may facilitate decision making about the appropriate use of biosimilars for patients with rheumatic and musculoskeletal diseases.

Title: Inadequate response or intolerability to oral methotrexate: Is it optimal to switch to subcutaneous methotrexate prior to considering therapy with biologics? Citation: Rheumatology international, May 2016, vol. 36, no. 5, p. 627-633, 1437-160X (May 2016) Author(s): Yadlapati, Sujani, Efthimiou, Petros Abstract: Methotrexate (MTX) is considered an anchor drug in the treatment of rheumatoid arthritis. It is also the first-line therapy in a multitude of rheumatologic conditions. Low-dose oral MTX is the preliminary modality of treatment for rheumatoid arthritis due to its affordability, favorable outcomes, and limited risks. However, patients refractory to low-dose MTX therapy may require larger doses of oral MTX. Several studies in the past have demonstrated variability in bioavailability of oral MTX at high doses. This warrants a subsequent switch to parenteral MTX. Widely used among the parenteral preparations of MTX is subcutaneous (SC) MTX. SC MTX provides dependable efficacy, predictable bioavailability, sustained clinical outcomes, and minimal GI adverse effects. It is useful either singularly or in combination therapy regimens. Although SC MTX and intramuscular MTX have similar pharmacokinetics, SC MTX may be preferred by most patients. Development of prefilled syringes and auto-injectors have enabled self-administration of the medication providing the patients with a sense of independence and improved general well-being. Hence, SC MTX can prove to be more efficacious in patients refractory to oral MTX therapy or in patients experiencing severe gastrointestinal adverse effects.

Title: Use of biologics in SLE: a review of the evidence from a clinical perspective. Citation: Rheumatology (Oxford, England), May 2016, vol. 55, no. 5, p. 775-779

Author(s): Aytan, Jayoti, Bukhari, Marwan A S Abstract: With the explosion in biologics use in rheumatology, newer and smarter ways of using these drugs in different diseases have been advocated. SLE has to date been at the back of the biologics algorithms. Recently, the US Food and Drug Administration and European Medicines Evaluation Agency licensed belimumab for use in SLE, the first drug in >30 years. A clinical review of the evidence that underlies the use of belimumab and other biologics in SLE reveals possible reasons why the results are not as spectacular as they are in other diseases. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Title: Biologic efficacy optimization-a step towards personalized medicine. Citation: Rheumatology (Oxford, England), May 2016, vol. 55, no. 5, p. 780-788 Author(s): Kiely, Patrick D W Abstract: This following is a review of the factors that influence the outcome of biologic agents in the treatment of adult RA and, when synthesized into the clinical decision-making process, enhance optimization. Adiposity can exacerbate inflammatory diseases; patients with high BMI have worse outcomes from RA, including TNF inhibitors (TNFis), whereas the efficacy of abatacept and tocilizumab is unaffected. Smoking adversely affects TNFi outcomes but has less or no effect on the efficacy of rituximab and tocilizumab, and the effect on abatacept is unknown. Patients who are positive for ACPA and RF have better efficacy with rituximab and abatacept than those who are seronegative, whereas the influence of serotype is less significant for tocilizumab and more complex for TNFis. All biologics seem to do better when co-prescribed with MTX, whereas in monotherapy, tocilizumab is superior to adalimumab and prescription of a non-MTX DMARD has advantages over no DMARD for rituximab and adalimumab. Monitoring of TNFi drug levels is an exciting new field, correlating closely with efficacy in RA and PsA, and is influenced by BMI, adherence, co-prescribed DMARDs and anti-drug antibodies. The measurement of trough levels provides a potential tool for patients who are not doing well to determine early whether to switch within the TNFi class (if levels are low) or to a biologic with an alternative mode of action (if levels are normal or high). Conversely, the finding of supratherapeutic levels has the potential to enable individual patient selection for dose reduction without the risk of flare.

Title: Is salivary gland ultrasonography a useful tool in Sjögren's syndrome? A systematic review. Citation: Rheumatology (Oxford, England), May 2016, vol. 55, no. 5, p. 789-800 Author(s): Jousse-Joulin, Sandrine, Milic, Vera, Jonsson, Malin V, Plagou, Athena, Theander, Elke, Luciano, Nicoletta, Rachele, Pascale, Baldini, Chiara, Bootsma, Hendrika, Vissink, Arjan, Hocevar, Alojzija, De Vita, Salvatore, Tzioufas, Athanasios G, Alavi, Zarin, Bowman, Simon J, Devauchelle-Pensec, Valerie, US-pSS Study Group Abstract: Ultrasonography (US) is a sensitive tool in the diagnosis of major salivary gland abnormalities in primary Sjögren's syndrome (pSS). The aim of this systematic review was to assess the metric properties of this technique. PUBMED and EMBASE databases were searched. All publications between January 1988 and January 2013 were considered. Data were extracted from

the articles meeting the inclusion criteria according to US definition of salivary gland scoring system and metric properties studied. The type and number of glands tested, study design and metric properties according to OMERACT filter (truth, discrimination, feasibility) were assessed. Of 167 publications identified initially with PUBMED and EMBASE, 31 met the inclusion criteria. The number of pSS patients varied among the studies from 16 to 140. The diagnosis of pSS was in line in most of the cases with the American-European Consensus Group (AECG) classification criteria for Sjögren's syndrome. The US examination was performed in suspected pSS only in studies in which the sensitivity ranged from 45.8 to 91.6% and specificity from 73 to 98.1%. There was heterogeneity in regard to the definition of US in B-mode and few studies used US in colour Doppler. Few studies reported reliability of US and sensitivity to change in pSS. US is a valuable tool for detecting salivary gland abnormalities in pSS. Its reliability has been poorly investigated and there is considerable variation in the definition of US abnormalities. Further studies are required to validate and standardize the US definition of salivary gland in pSS.

Title: Personalized biological treatment for rheumatoid arthritis: a systematic review with a focus on clinical applicability. Citation: Rheumatology (Oxford, England), May 2016, vol. 55, no. 5, p. 826-839 Author(s): Cuppen, Bart V J, Welsing, Paco M J, Sprengers, Jan J, Bijlsma, Johannes W J, Marijnissen, Anne C A, van Laar, Jacob M, Lafeber, Floris P J G, Nair, Sandhya C Abstract: To review studies that address prediction of response to biologic treatment in RA and to explore the clinical utility of the studied (bio)markers. A search for relevant articles was performed in PubMed, Embase and Cochrane databases. Studies that presented predictive values or in which these could be calculated were selected. The added value was determined by the added value on prior probability for each (bio)marker. Only an increase/decrease in chance of response ⩾15% was considered clinically relevant, whereas in oncology values >25% are common. Of the 57 eligible studies, 14 (bio)markers were studied in more than one cohort and an overview of the added predictive value of each marker is presented. Of the replicated predictors, none consistently showed an increase/decrease in probability of response ⩾15%. However, positivity of RF and ACPA in case of rituximab and the presence of the TNF-α promoter 308 GG genotype for TNF inhibitor therapy were consistently predictive, yet low in added predictive value. Besides these, 65 (bio)markers studied once showed remarkably high (but not validated) predictive values. We were unable to address clinically useful baseline (bio)markers for use in individually tailored treatment. Some predictors are consistently predictive, yet low in added predictive value, while several others are promising but await replication. The challenge now is to design studies to validate all explored and promising findings individually and in combination to make these (bio)markers relevant to clinical practice.

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