welcome and overview - forefront...

Welcome and Overview

Advances in the Treatment of Psoriasis

Neil Korman, MD, PhDDirector, Clinical Trials Unit

Clinical Director, Murdough Family Center for Psoriasis

Professor, DermatologyUniversity Hospitals Cleveland

Medical CenterCase Western Reserve University

School of MedicineCleveland, Ohio

Disclosure: Neil Korman, MD, PhD

Dr. Korman is an investigator, advisor, speaker, and or consultant for AbbVie, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Prothena, Regeneron, Sun Pharma, Valeant Pharmaceuticals International, and Regeneron

Trends in Biologic Use in Psoriasis in the United States

AAD=American Academy of Dermatology. NPF=National Psoriasis Foundation. Menter A, et al. J Am Acad Dermatol. 2008;58:826-850. Hsu S, et al. Arch Dermatol. 2012;148(1):95-102.

Step therapy Phototherapy

Then oral systemics

Then biologics

Phototherapy or oral systemics

or biologics

Both the AAD and the NPF support the use of biologics as a first-line agent for patients with moderate to severe psoriasis

Considerations Prior to Initiating Systemic Therapy in Patients With Psoriasis

TB=tuberculosis. CHF=congestive heart failure. TNF=tumor necrosis factor.

Assess for TB

Screen for hepatitis B and C

viral infections

Assess underlying cancer risk

Use caution in patients with

active CHF when considering

medications with TNF inhibitors

Verify absence of demyelinating

disease

Use caution in patients with CD/UC when considering

medications with IL-17 inhibitors

Verify absence of current infection

Consider completing

all age-appropriate

immunizations

FDA-Approved Biologics

PsA=psoriatic arthritis. IL=interleukin. FDA=US Food and Drug Administration.

Drug Class Agent

TNF antagonistsEtanerceptInfliximab

Adalimumab

Psoriasis, PsAPsoriasis, PsAPsoriasis, PsA

p40 IL-12/23 antagonist Ustekinumab Psoriasis, PsA

IL-17 antagonistsSecukinumabIxekizumab

Psoriasis, PsAPsoriasis

Indication

Brodalumab Psoriasis

IL-23 Blockers: Biologics on the Horizon

3 different IL-23 agents in development

Guselkumab Tildrakizumab Risankizumab

Phase 2 efficacy and safety data as well as some phase 3 data are very promising

IL-17 Inhibitors

IgG=immunoglobulin G.Gaspari AA, et al. Dermatol Ther. 2015;28(4):179-193.

Secukinumab Ixekizumab Brodalumab

Fully human IgG1 monoclonal

antibody

Neutralizes IL-17A

Approved for psoriasis and PsA

Humanized IgG4 monoclonal

antibody

Neutralizes IL-17A

Approved for psoriasis

Human anti–IL-17A

receptor monoclonal

antibody

Approved for psoriasis

Ustekinumab

Secukinumab

Secukinumab

Ixekizumab

Guselkumab

Superior Agent

Short-Term Head-to-Head Clinical Trials Among Biologics Used for Psoriasis

*All doses used are FDA-approved doses. Etanercept dose is the high-dose 50 mg twice weekly for the first 3 months.Blauvelt A et al. J Am Acad Dermatol. 2017;76:60-69. Gordon KB et al. N Engl J Med. 2015; 373:136-144. Griffiths CE at el. N Engl J Med. 2010:362:118-128. Griffiths CEM et al. Lancet. 2015;386:541-551. Langley RG et al. N Engl J Med. 2014;371: 326-338. Lebwohl M et al. N Engl J Med. 2015;373:1318-1328. New head-to-head data. 2017. https://investor.lilly.com/releasedetail.cfm?ReleaseID=1015859.

Ustekinumab vs etanercept

Secukinumab vs etanercept

Secukinumab vs ustekinumab

Ixekizumab vs etanercept

Guselkumab vs adalimumab

BrodalumabBrodalumab vs ustekinumab

IxekizumabIxekizumab vs ustekinumab

Treat to Target: The National Psoriasis Foundation Consensus

BSA=body surface area.Armstrong AW et al. J Am Acad Dermatol. 2017;76(2):290-298.

Preferred Assessment Tool in Clinical Practice BSA

Time at initial evaluation after treatment initiationAt 3 months

after initiation

Acceptable response at 12 weeks after treatment initiationEither BSA 3% orBSA improvement 75% from baseline

Target response at 12 weeks after treatment initiation BSA 1%

Time interval for evaluation during maintenance therapy Every 6 months

Target response during maintenance therapy BSA 1%

Unmet Needs in Psoriasis Still Exist

Lebwohl et al. Am J Clin Derm. 2016;17:87-97.

Patients report that itching is the most important factor in disease severity, while physicians report that size and severity of lesions are most important in disease severity

Patients with psoriasis must be regularly screened for PsA, and tools are needed to separate PsA from other rheumatic diseases

Ongoing communication between patients and physicians is needed for better understanding of choice of therapies

Summary: Treatment of Moderate to Severe Psoriasis

Options are increasing with inhibitors to TNF,

IL12/23, or IL17; among the currently

approved biologics at the currently approved doses, IL-17-blocking agents appear to be

most efficacious

Comparative effectiveness studies and consideration of

comorbidities are critical in determining

optimal therapy for individual patients

New biologics targeting IL-23 are

in development

Psoriasis Therapeutics From the 1950s to the Present:

Enter the Renaissance

Bruce E. Strober, MD, PhDProfessor and Chair,

Department of DermatologyUniversity of Connecticut Health Center

Farmington, Connecticut

Disclosure: Bruce E. Strober, MD, PhD

Dr. Strober is a consultant and or advisor for AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Celgene, Cutanea-Maruho, Dermira, Lilly, Janssen, Leo Pharma, Medac Pharma, Novartis, Pfizer, Sun Pharma, UCB, and Valeant Pharmaceuticals International, and is the Scientific Director for the Corrona/NPF Psoriasis Patient Registry

Game Rules

Your knowledge of psoriasis therapeutics and disease pathogenesis will be tested through a series of 10 questions

• Each question starts out worth 10 points, but the point value decreases with time so think fast!

• The score for each question is calculated by taking the total team points and dividing by the number of team members

• At halftime, you’ll be able to see how you are stacking up against your competition

• The team with the most points at the end wins bragging rights

• There will also be a Team MVP for each team—the individual with the highest overall score

Methotrexate

Molecular weight454.45 g/mol

Methotrexate (cont.)

Therapeutic Suppression of Tissue Activity II. Effect of Aminopterin (4-aminopteroylglutamic acid) in Rheumatoid Arthritis and Psoriasis

Gubner R, August S, Ginsberg V

Gubner R, August S, Ginsberg V. Therapeutic suppression of tissue reactivity. II. Effect of aminopterin in rheumatoid arthritis and psoriasis. Am J Med Sci. 1951;221(2):176-182.

1951

Methotrexate

Structurally similar to folic acid

Irreversible inhibition Reversible inhibition

Dihydrofolate reductase

Thymidylate synthetase

Folic acid tetrahydrofolate DNA

Methotrexate: Adenosine Metabolism

• Methotrexate is metabolized to polyglutamate derivatives potent inhibitors of AICAR transformylase

• Accumulation of AICAR inhibits adenosine deaminase and AMP deaminase increased concentrations of adenosine

• Adenosine binds to 1 or more of 4 known receptors (A1, A2a, A2b, and A3) that have anti-inflammatory effects

AICAR=5-aminoimidazole-4-carboxamide ribonucleotide. AMP=adenosine monophosphate.Chan ES, Cronstein B. Arthritis Res. 2002;4:266-273. Montesinos MC et al. Arthritis Rheum. 2003;48:240-247. Morgan SL et al. Arthritis Rheum. 2004;50:3104-3111. Whittle SL, Hughes RA. Rheumatology. 2004;43:267-271.

Methotrexate: Adenosine Metabolism

• Methotrexate is metabolized to polyglutamate derivatives potent inhibitors of AICAR transformylase

• Accumulation of AICAR inhibits adenosine deaminase and AMP deaminase increased concentrations of adenosine

• Adenosine binds to 1 or more of 4 known receptors (A1, A2a, A2b, and A3) that have anti-inflammatory effects

• Methotrexate increases the amount of adenosine, an endogenous anti-inflammatory compound

AICAR=5-aminoimidazole-4-carboxamide ribonucleotide. AMP=adenosine monophosphate.Chan ES, Cronstein B. Arthritis Res. 2002;4:266-273. Montesinos MC et al. Arthritis Rheum. 2003;48:240-247. Morgan SL et al. Arthritis Rheum. 2004;50:3104-3111. Whittle SL, Hughes RA. Rheumatology. 2004;43:267-271.

Etretinate and Acitretin

EtretinateMolecular weight

354.48 g/mol

AcitretinMolecular weight

326.43 g/mol

Etretinate and Acitretin (cont.)

A Double-Blind Comparison of Acitretin and Etretinate in the Treatment of Severe Psoriasis

Results of a Nordic Multicentre Study

Kragballe K, Jansén CT, Geiger JM, Bjerke JR, Falk ES, Gip L, Hjorth N, Lauharanta J, Mork NJ, Reunala T, et al.

Kragballe K, Jansen CT, Geiger JM, et al. A double-blind comparison of acitretin and etretinate in the treatment of severe psoriasis. Results of a Nordic multicentre study. Acta Derm Venereol. 1989;69(1):35-40.

1989

Etretinate and Acitretin

Induce differentiation and inhibit

proliferation of keratinocytes

Have no immunosuppressive

activity

Have low efficacy as monotherapy and at tolerable (lower) doses

Cyclosporine


Cyclosporine (cont.)

Cyclosporine for Plaque-Type Psoriasis

Results of a Multidose, Double-Blind Trial

Ellis C, Fradin M, Messana J, Brown M, Siegel M, Howland Hartley A, Rocher L, Wheeler S, Hamilton T, Parish T, Ellis-Madu M, Duell E, Annesley T, Cooper K, Voorhees J

Ellis CN, Fradin MS, Messana JM, et al. Cyclosporine for plaque-type psoriasis. Results of a multidose, double-blind trial. N Engl J Med. 1991;324(5):277-284.

1991

Cyclosporine: Mechanism of Action

IL=interleukin.

Selectively inhibits production of IL-2 and other

proinflammatorycytokines

Prevents T-cell activation

Is broadly acting immunosuppressant

TNF-α Inhibitors

Molecular weight=144 kDa

Antigen (TNF)binding sites

TNF receptors(TNF binding sites)

Anti-TNFmonoclonal antibody

Soluble TNF receptor:Fc fusion protein

Fc fragment Fc fragment

Infliximab and adalimumab Etanercept

Molecular weight=51 kDa

TNF=tumor necrosis factor.

Infliximab

Efficacy and Safety of Infliximab Monotherapy for Plaque-Type Psoriasis: A Randomized Trial

Early Report

Chaudhari U, Romano P, Mulcahy LD, Dooley LT, Baker DG, Gottlieb AB

Chaudhari U, Romano P, Mulcahy LD, Dooley LT, Baker DG, Gottlieb AB. Efficacy and safety of infliximab monotherapy for plaque-type psoriasis: a randomised trial. Lancet. 2001;357(9271):1842-1847.

2001

Etanercept

A Randomized Trial of Etanercept as Monotherapy for Psoriasis

Gottlieb AB, Matheson RT, Lowe N, Krueger GG, Kang S, Goffe BS, Gaspari AA, Ling M, Weinstein GD, Nayak A, Gordon KB, Zitnik R

Gottlieb AB, Matheson RT, Lowe N, et al. A randomized trial of etanercept as monotherapy for psoriasis. Arch Dermatol. 2003;139(12):1627-1632; discussion 1632.

2003

Adalimumab

Adalimumab Therapy for Moderate to Severe Psoriasis: A Randomized, Controlled Phase III Trial

Menter A, Tyring SK, Gordon K, Kimball AB, Leonardi CL, Langley RG, Strober BE, Kaul M, Gu Y, Okun M, Papp K

Menter A, Tyring SK, Gordon K, et al. Adalimumab therapy for moderate to severe psoriasis: A randomized, controlled phase III trial. J Am Acad Dermatol. 2008;58(1):106-115.

2008

Current Model of Psoriasis Immunopathogenesis

GM-CSF=granulocyte/macrophage-colony stimulating factor.Keijsers RR et al. Br J Dermatol. 2013;168:1294-1302. Lin AM et al. J Immunol. 2011;187:490-500. Res PCM et al. PloS ONE. 2010;5:e14108. Taylor PR et al. Nat Immunol. 2014;15:143-151.

Stressed keratinocytes

Myeloid dendritic cell

Activation

T cells

Keratinocytes

TNF-α

IL-1BIL-6

TNF-α

IL-17A/FIL-22

GM-CSF

IL-23IL-12

TNF-α Inhibitors

Leads to the induction of an inflammatory milieu that accelerates

keratinocyte proliferation epidermal hyperplasia

Angiogenic tissue reaction leading to increased skin vascularization

An inflammatory cellular infiltrate

IFN=interferon. Th1=Type 1 T helper.

Inhibits the activity of TNF-α

Autoreactive Th1 cells

produce IFN-and TNF-α

TNF-α inhibitors reverse all of

the above

Demonstrate a dose-response

effect in clearing psoriasis

TNF-α

T-Cell Inhibitors

A Randomized, Double-Blind, Placebo-Controlled Phase III Study Evaluating Efficacy and Tolerability of 2 Courses of Alefacept in Patients With Chronic Plaque Psoriasis

Krueger GG, Papp KA, Stough DB, Loven KH, Gulliver WP, Ellis CN;Alefacept Clinical Study Group

Krueger GG, Papp KA, Stough DB, Loven KH, Gulliver WP, Ellis CN. A randomized, double-blind, placebo-controlled phase III study evaluating efficacy and tolerability of 2 courses of alefacept in patients with chronic plaque psoriasis. J Am Acad Dermatol. 2002;47(6):821-833.

2002

T-Cell Inhibitors (cont.)

Efalizumab for Patients With Moderate to Severe Plaque Psoriasis

A Randomized Controlled Trial

Gordon KB, Papp KA, Hamilton TK, Walicke PA, Dummer W, Li N, Bresnahan BW, Menter A; Efalizumab Study Group

Gordon KB, Papp KA, Hamilton TK, et al. Efalizumab for patients with moderate to severe plaque psoriasis: a randomized controlled trial. JAMA. 2003;290(23):3073-3080.

2003

T-Cell Inhibitors

Low efficacy drugs with variable safety concerns

and monitoring requirements

No longer available

IL-12/23 (p40) Inhibitors

Efficacy and Safety of Ustekinumab, a Human Interleukin-12/23 Monoclonal Antibody, in Patients With Psoriasis: 76-Week Results From a Randomized, Double-Blind, Placebo-Controlled Trial (PHOENIX 1)Leonardi CL, Kimball AB, Papp KA, Yeilding N, Guzzo C, Wang Y, Li S, Dooley LT, Gordon KB; PHOENIX 1 study investigators

Leonardi CL, Kimball AB, Papp KA, et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1). Lancet. 2008;371(9625):1665-1674.Papp KA, Langley RG, Lebwohl M, et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2). Lancet. 2008;371(9625):1675-1684.

Efficacy and Safety of Ustekinumab, a Human Interleukin-12/23 Monoclonal Antibody, in Patients With Psoriasis: 52-Week Results From a Randomized, Double-Blind, Placebo-Controlled Trial (PHOENIX 2)Papp KA, Langley RG, Lebwohl M, Krueger GG, Szapary P, Yeilding N, Guzzo C, Hsu MC, Wang Y, Li S, Dooley LT, Reich K; PHOENIX 2 study investigators

2008

IL-12/23 (p40) Inhibitors (cont.)

Comparison of Ustekinumab and Etanercept for Moderate to Severe Psoriasis

Griffiths CE, Strober BE, van de Kerkhof P, Ho V, Fidelus-Gort R, Yeilding N, Guzzo C, Xia Y, Zhou B, Li S, Dooley LT, Goldstein NH, Menter A; ACCEPT Study Group

Griffiths CE, Strober BE, van de Kerkhof P, et al. Comparison of ustekinumab and etanercept for moderate-to-severe psoriasis. N Engl J Med. 2010;362(2):118-128.

2010

IL-12/23 (p40) Inhibitors (cont.)

Efficacy and Safety Results From a Phase III, Randomized Controlled Trial Comparing the Safety and Efficacy of Briakinumab With Etanercept and Placebo in Patients With Moderate to Severe Chronic Plaque Psoriasis

Strober BE, Crowley JJ, Yamauchi PS, Olds M, Williams DA

Strober BE, Crowley JJ, Yamauchi PS, Olds M, Williams DA. Efficacy and safety results from a phase III, randomized controlled trial comparing the safety and efficacy of briakinumab with etanercept and placebo in patients with moderate to severe chronic plaque psoriasis. Br J Dermatol. 2011;165(3):661-668.

2011





Activation

T cells

Keratinocytes

TNF-α

IL-1BIL-6

TNF-α

IL-17A/FIL-22

GM-CSF

IL-23IL-12

Molecular Weight = 460.5

Apremilast


Apremilast

Apremilast, an Oral Phosphodiesterase 4 (PDE4) Inhibitor, in Patients With Moderate to Severe Plaque Psoriasis: Results of a Phase III Randomized Controlled Trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM 1])

Papp K, Reich K, Leonardi CL, Kircik L, Chimenti S, Langley RG, Hu C, Stevens RM, Day RM, Gordon KB, Korman NJ, Griffiths CE

Papp K, Reich K, Leonardi CL, et al. Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: Results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1). J Am Acad Dermatol. 2015;73(1):37-49.

2015

Apremilast (cont.)

Efficacy and Safety of Apremilast, an Oral Phosphodiesterase 4 Inhibitor, in Patients With Moderate to Severe Plaque Psoriasis: Over 52 Weeks: A Phase III Randomized Controlled Trial (ESTEEM 2)

Paul C, Cather J, Gooderham M, Poulin Y, Mrowietz U, Ferrandiz C, Crowley J, Hu C, Stevens RM, Shah K, Day RM, Girolomoni G, Gottlieb AB

Paul C, Cather J, Gooderham M, et al. Efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with moderate-to-severe plaque psoriasis over 52 weeks: a phase III, randomized controlled trial (ESTEEM 2). Br J Dermatol. 2015;173(6):1387-1399.

2015

Apremilast: Mode of Action

cAMP=cyclic adenosine monophosphate.

Proinflammatory

mediators

(ie, TNF-α,

IL-23, IFN-γ)

Anti-inflammatory

mediators

(ie, IL-10)

cAMP

AMP

AMP

AMP

PDE4

Apremilast: Mode of Action (cont.)

Proinflammatory

mediators

(ie, TNF-α,

IL-23, IFN-γ)

Anti-inflammatory

mediators

(ie, IL-10)

Apremilast

cAMP

AMP

PDE4

cAMP

cAMP

IL-17 Inhibitors

Secukinumab in Plaque Psoriasis: Results of 2 Phase III Trials

Langley RG, Elewski BE, Lebwohl M, Reich K, Griffiths CE, Papp K, Puig L, Nakagawa H, Spelman L, Sigurgeirsson B, Rivas E, Tsai TF, Wasel N, Tyring S, Salko T, Hampele I, Notter M, Karpov A, Helou S, Papavassilis C; ERASURE Study Group; FIXTURE Study Group

Langley RG, Elewski BE, Lebwohl M, et al. Secukinumab in plaque psoriasis--results of two phase 3 trials. N Engl J Med. 2014;371(4):326-338.

2014

IL-17A/FIL-22

GM-CSF

IL-17 Inhibitors (cont.)

Phase III Trials of Ixekizumab in Moderate to Severe Plaque Psoriasis

Gordon KB, Blauvelt A, Papp KA, Langley RG, Luger T, Ohtsuki, K Reich,Amato D, Ball SG, Braun DK, Cameron GS, Erickson J, Konrad RJ, Muram TM, Nickoloff, Osuntokun OO, Secrest RJ, Zhao F, Mallbris L, Leonardi CL; UNCOVER-1, UNCOVER-2; UNCOVER-3 Study Groups

Gordon KB, Blauvelt A, Papp KA, et al. Phase 3 Trials of Ixekizumab in Moderate-to-Severe Plaque Psoriasis. N Engl J Med. 2016;375(4):345-356.

2016

IL-17 Inhibitors (cont.)

Phase 3 Studies Comparing Brodalumab With Ustekinumab in Psoriasis

Lebwohl M, Strober B, Menter A, Gordon K, Weglowska J, Puig L, Papp K, Spelman L, Toth D, Kerdel F, Armstrong AW, Stingl G, Kimball AB, Bachelez H, Wu JJ, Crowley J, Langley, Blicharski T, Paul C, Lacour JP, Tyring S, Kircik L, Chimenti S, Duffin KC, Bagel J, Koo J, Aras G, Li J, Song W, MIlmont CE, Shi Y, Erondu N, Klelotka P, Kotzin B, Nirula A

Lebwohl M, Strober B, Menter A, et al. Phase 3 Studies Comparing Brodalumab with Ustekinumab in Psoriasis. N Engl J Med. 2015;373(14):1318-1328.

2015





Activation

T cells

Keratinocytes

TNF-α

IL-1BIL-6

TNF-α

IL-17A/FIL-22

GM-CSF

IL-23IL-12

IL-23 (p19) Inhibitors

A Phase II Trial of Guselkumab vs Adalimumab for Plaque Psoriasis

Gordon KB, Duffin KC, Bissonnette R, Prinz JC, Wasfi Y, Li S, Shen YK, Szapary P, Randazzo B, Reich K

Gordon KB, Duffin KC, Bissonnette R, et al. A phase 2 trial of guselkumab versus adalimumab for plaque psoriasis. N Engl J Med. 2015;373(2):136-144.

2015

IL-23IL-12

Tildrakizumab (MK-3222), an Anti-Interleukin-3p19 Monoclonal Antibody, Improves Psoriasis in a Phase IIbRandomized Placebo-Controlled TrialPapp K, Thaçi D, Reich K, Riedl E, Langley RG, Krueger JG, Gottlieb AB, Nakagawa H, Bowman EP, Mehta A, Li Q, Zhou Y, Shames R

Papp K, Thaci D, Reich K, et al. Tildrakizumab (MK-3222), an anti-interleukin-23p19 monoclonal antibody, improves psoriasis in a phase IIb randomized placebo-controlled trial. Br J Dermatol. 2015;173(4):930-939. Krueger JG, Ferris LK, Menter A, et al. Anti-IL-23A mAb BI 655066 for treatment of moderate-to-severe psoriasis: Safety, efficacy, pharmacokinetics, and biomarker results of a single-rising-dose, randomized, double-blind, placebo-controlled trial. J Allergy Clin Immunol. 2015;136(1):116-124 e117.

Anti-IL-23A mAB BI 655066 for Treatment of Moderate to Severe Psoriasis: Safety, Efficacy, Pharmacokinetics, and Biomarker Results of a Single-Rising-Dose, Randomized, Double-Blind, Placebo-Controlled TrialKrueger JG, Ferris LK, Menter A, Wagner F, White A, Visvanathan S, Lalovic B, Aslanyan S, Wang EE, Hall D, Solinger A, Padula S, Scholl P (Pulled from NCBI)

2015

IL-23 (p19) Inhibitors (cont.)

Clinical Case Roundtable

Linda Stein Gold, MDDirector of Dermatology Clinical Research,

Division Head, DermatologyHenry Ford Health System

Detroit and West Bloomfield, Michigan

Disclosure: Linda Stein Gold, MD

Dr. Stein Gold is an investigator, advisor, and or consultant for Celgene, GSK, Leo Pharma, Novartis, Taro, and Valeant Pharmaceuticals International

10-year history of psoriasis

and PsA

Was started on etanercept in 2011; did well for 2 years but flared

in 2013

This photo is not the actual patient.

CASE 1: Mr. Melfor, 48-Year-Old White Man

PMH: HTN,

BMI=35

The patient stopped adalimumab himself and

was subsequently admitted to psoriasis day hospital

with 90% TBSA

Images: Courtesy of Dr. Linda Stein Gold.PsA=psoriatic arthritis. PMH=past medical history. HTN=hypertension. BMI=body mass index. TBSA=total body surface area.

The patient was switched to adalimumab; after 6 weeks, his joints improved but his

skin was still flaring

Comparison of Ustekinumab and Etanercept for Moderate to Severe Psoriasis

Griffiths CE et a. N Engl J Med. 2010;362:118-128.

0

20

40

60

80

100

0 2 4 6 8 10 12

*P<0.001†P=0.01

†*

**

Week

% o

f P

atie

nts

At Least 75% Improvement in PASI Score

0

20

40

60

80

100

0 16 20 24 28 32

Week

% o

f P

atie

nts

At Least 75% Improvement in PASI Score

Crossover to ustekinumab 90 mg after no response to etanercept

Among patients who did not have a response to etanercept:

48.9%had at least 75% improvement in the PASI score and 23.4%

had at least 90% improvement after crossing over to ustekinumab 90 mg for 12 weeks

Ustekinumab 90 mg (N=347)

Ustekinumab 45 mg (N=209)

Etanercept (N=347)

TNFi Primary Failure Predicts Decreased Ustekinumab Efficacy in Patients With Psoriasis

TNFi=tumor necrosis factor inhibitor. Sorensen EP et al. J Drugs Dermatol. 2015;14(8):893-898.

Retrospective study: 44 patients with psoriasis treated with ustekinumab who had 1 previous TNFi exposure

Result: Among patients with psoriasis previously exposed to TNFi, a history of a previous TNFi primary failure predicts a decreased response to ustekinumab independent of patient demographics and medical comorbidities

Success After Anti-TNF Failure

58.150.7

55.2

42.044.6

29.4 30.827.5

21.217.8 20.7

12.5

1.3 0.7 0.0 1.80

20

40

60

80

100

No Previous Biologic(n=1889)

Previous Biologic(n=498)

Biologic Without Failure(n=307)

Biologic With Failure(n=191)

Secukinumab 300 mg Secukinumab 150 mg Etanercept Placebo

% o

f S

ubje

cts

With R

esponse

PASI 90 Response

*P<0.0001 vs placebo. †P=0.0001 vs placebo. ‡P<0.0001 vs etanercept. §P=0.0001 vs etanercept. ||P<0.01 vs etanercept. ¶P<0.05 vs etanercept.Missing data were imputed as nonresponse. n=number of evaluable subjects.PASI= Psoriasis Area and Severity Index. PASI 90=90% improvement from baseline PASI score.Griffiths C et al. J Am Acad Dermatol. 2015;72(5):AB251.

*‡

*‡

*

*§

*

*

*||

*

†

*¶

*

SCULPTURE: Secukinumab Treatment—Adverse EventsSafety Remains Consistent Through 4 Years

AEs=adverse events. TB=tuberculosis. MACE=major adverse cardiac event. NMSC=nonmelanoma skin cancer.*1 case was an exacerbation of previously existing ulcerative colitis. †1 case of cholangiocarcinoma, 1 case of invasive ductal breast carcinoma .Bissonnette R, et al. 25th Congress of EADV, 28 September–2 October 2016, Vienna, Austria. Oral Presentation.Mrowietz U, et al; SCULPTURE Study Group. J Am Acad Dermatol. 2015;73(1):27-36.

Treatment Emergent AEsYear 1 n=168n (%)

Year 2n=168n (%)

Year 3n=157n (%)

Year 4n=142n (%)

Selected Less Frequent AEs

Opportunistic infections (other than TB and candidiasis) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)

Tuberculosis 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)

Candida infections

Vulvovaginal candidiasis 3 (1.8) 3 (1.8) 1 (0.6) 0 (0.0)

Oral candidiasis 0 (0.0) 1 (0.6) 0 (0.0) 1 (0.7)

Neutropenia 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)

MACE 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)

Crohn’s disease 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)

Ulcerative colitis 0 (0.0) 2 (1.2)* 1 (0.6) 0 (0.0)

Malignant or unspecified tumors (excluding NMSC) 0 (0.0) 2 (1.2)† 0 (0.0) 0 (0.0)

Ixekizumab (IXE) vs Etanercept (ETN) by Prior Biologic Exposure

50.7

24.3

7.0

34.6

13.2

3.7

82.2

64.4

34.9

76.2

55.2

25.2

87.7

67.7

37.0

91.5

76.1

47.2

0

20

40

60

80

100

PASI 75 PASI 90 PASI 100

% o

f P

atients

PASI Response Rates (NRI)

N=total number of patients. NRI=nonresponder imputation. Q4W=every 4 weeks. Q2W=every 2 weeks.Gottlieb AB et al. 2016 Fall Clinical Dermatology Conference.

ETN biologic naïve (N=604)ETN biologic experienced (N=136)

IXE Q4W biologic naïve (N=590)IXE Q4W biologic experienced (N=136)

IXE Q2W biologic naïve (N=594)IXE Q2W biologic experienced (N=142)

Both doses of ixekizumab provided higher efficacy compared to etanercept regardless of previous biologic use

P<0.001 for all comparisons between IXE and ETN

Safety Summary: Selected AEs of Special Interest

TEAE=treatment-emergent adverse event. SAE=serious adverse event. MI=myocardial infarction.*No deaths were observed. †This case was adjudicated as “probable” but classified as a diagnosis per EPIMAD criteria. ‡These cases were adjudicated as “definitive.”Gottlieb AB et al. 2016 Fall Clinical Dermatology Conference.

Placebo ETN IXE Q4W IXE Q2W

Biologic naïven (%)

Biologic experienced

n (%)



n (%)



n (%)



n (%)

1 TEAE 126 (44.4) 34 (44.7) 324 (53.6) 75 (55.6) 341 (58.2) 78 (54.5) 346 (58.4) 78 (54.9)

1 SAE* 6 (2.1) 1 (1.3) 12 (2.0) 2 (1.5%) 12 (2.0) 2 (1.4) 12 (2.0) 2 (1.4)

Infections 31 (20.5) 5 (14.3) 67 (22.9) 17 (28.8) 66 (24.1) 12 (23.5) 76 (25.9) 14 (25.9)

Oral candidiasis 0 (0.0) 0 (0.0) 1 (0.3) 0 (0.0) 0 (0.0) 0 (0.0) 2 (0.7) 1 (1.9)

Vulvovaginal candidiasis 0 (0.0) 0 (0.0) 0 (0.0) 1 (4.0) 1 (1.2) 0 (0.0) 0 (0.0) 0 (0.0)

Skin candida 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (0.3) 0 (0.0)

MACE: Acute MI 1 (0.4) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)

Crohn’s disease 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (0.2)† 0 (0.0)

Ulcerative colitis 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (0.4)‡ 0 (0.0)

CASE 1: Mr. Melfor, 48-Year-Old White Man

Patient started on ustekinumab 90 mg

After 4 weeks, PASI 50

After 12 weeks, PASI 90

Case 2: Mr. Rodder, 22-Year-Old White Man

He is heading out of state for graduate school and would like to discuss other options for psoriasis

History of extensive psoriasis

Has been on phototherapy and methotrexate in

the past

This photo is not the actual patient.

Has Crohn’s disease; well

controlled with sulfasalazine

TNFi and IBD

TNF plays a central role in the pathogenesis of CD and UC

High levels of TNF-α are found in the stool, lamina propria, and blood of patients with active disease

Inhibition of TNF-α with neutralizing monoclonal antibodies reduces disease activity in both CD and UC

FDA approved treatments for IBD include:

• Infliximab• CD (pediatric and adult)

• UC (pediatric and adult)

• Adalimumab• CD (pediatric and adult)

• UC (adult)

• Ustekinumab• CD (adult)

IBD=inflammatory bowel disease. CD=Crohn’s disease. UC=ulcerative colitis.Fréling E et al. Am J Gastroenterol. 2015;110(8):1186-1196. Singh S et al. Clin Gastroenterol Hepatol. 2016;14(8):1120-1129.

Secukinumab Long-Term Safety Experience: A Pooled Analysis of 10 Phase II and III Clinical Studies in Patients With Moderate to Severe Plaque Psoriasis

van de Kerkhof PC, Griffiths CE, Reich K, Leonardi CL, Blauvelt A, Tsai TF, Gong Y, Huang J, Papavassilis C, Fox T

van de Kerkhof PC, Griffiths CE, Reich K, et al. J Am Acad Dermatol. 2016;75(1):83-98.

Secukinumab and IBD: Background and Objectives

• Patients with psoriasis are up to 4 times more likely than the general population to have CD1

• The role of IL-17A in IBD is unclear2,3

• Secukinumab has been shown to be ineffective in treating patients with CD4

• IBD, including CD and UC, was analyzed in a set of pooled safety data from 10 clinical studies of secukinumab in subjects with moderate to severe plaque psoriasisand in the subgroup with a prior history of IBD

1. Li WQ et al. Ann Rheum Dis. 2013;72:1200-1205. 2. Skroza N et al. Biomed Res Int. 2013;2013:983902.3. O‘Connor W Jr et al. Nat Immunol. 2009;10:603-609. 4. Hueber W et al. Gut. 2012;61:1693-1700.

Methodology Relevant for IBD Analysis

Subjects: Subjects with prior or ongoing CD were allowed to participate in secukinumab psoriasis studies

Analysis: A broad search using IBD narrow NMQ consisting of 32 relevant preferred terms was performed to ensure all suspected cases of CD and UC were retrieved

NMQ=Novartis MedDRA Query.van de Kerkhof PC et al. J Am Acad Dermatol. 2016;75(1):83-98.

Incidence of IBD (CD and UC) Across Treatments in First 12 Weeks

Secukinumab 300 mg*(n=1173)

Secukinumab150 mg*(n=1174)

Secukinumab 300 mg, 150 mg, or Other Doses†

(n=2877)Etanercept‡

(n=323)Placebo(n=793)

Incidence Overall, n (%) (95% CI)

IBD1 (0.09)

(0, 0.55)

1 (0.09)

(0, 0.55)

2 (0.07)

(0.01, 0.28)

1 (0.3)

(0, 2.0)

0

(0, 0.6)

CD0

(0, 0.41)

1 (0.09)

(0, 0.55)

1 (0.03)

(0, 0.23)

0

(0, 1.5)

0

(0, 0.6)

UC1 (0.09)

(0, 0.55)

0

(0, 0.41)

1 (0.03)

(0, 0.23)

1 (0.3)

(0, 2.0)

0

(0, 0.6)

*Includes subjects from phase 3 studies only who were randomized to the specified secukinumab dose at the study start. †Includes subjects from phase 2 and 3 studies who were randomized to any dose of secukinumab at the study start. ‡Etanercept data are from 1 pivotal phase 3 study, FIXTURE.van de Kerkhof PC et al. J Am Acad Dermatol. 2016;75(1):83-98.

Exposure-Adjusted IR of IBD (CD and UC) Across Treatments for 52 Weeks

Any Secukinumab 300 mg*(n=1410)


Secukinumab 300 mg, 150 mg, or Other Doses†


(n=323)

Exposure-Adjusted Incidence Overall, n (IR) (95% CI)

IBD§ 3 (0.26)

(0.05, 0.75)

4 (0.35)

(0.10, 0.90)

9 (0.33)

(0.15, 0.63)

1 (0.34)

(0.01, 1.90)

CD0

(0, 0.31)

2 (0.18)

(0.02, 0.63)

3|| (0.11)

(0.02, 0.32)

0

(0, 1.26)

UC2 (0.17)

(0.02, 0.61)

2 (0.18)

(0.02, 0.63)

4|| (0.15)

(0.04, 0.38)

1 (0.34)

(0.01, 1.90)

IR=incidence rate per 100 subject-years. *Includes subjects from phase 3 studies only who were randomized to the specified secukinumab dose at the study start and subjects on placebo who were rerandomized to secukinumab at Week 12. †Includes subjects from phase 2 and 3 studies who were randomized to any dose of secukinumab at the study start and subjects on placebo who were re-randomized to secukinumab at Week 12. ‡Etanercept data are from 1 pivotal phase 3 trial, FIXTURE. §“Anal fistula” and “sclerosing cholangitis,” although not true IBDs, were also retrieved because of the broad search criteria applied. ||2 of the 3 cases of CD had a prior history of CD, and the third case was in a subject who had gastrointestinal symptoms at baseline suggestive of undiagnosed active CD–the event resolved with therapy and did not cause study treatment discontinuation; 2 of the 4 UC cases had a prior history of UC. van de Kerkhof PC et al. J Am Acad Dermatol. 2016;75(1):83-98.

IBD Reported During Entire 52 Weeks

3 cases of CD (2 flares and 1 new event, all on secukinumab 150 mg) were identified over 52 weeks of treatment1

• 1 flare occurred during the first 12 weeks in a subject with long-standing CD; the event resolved with therapy

• Another flare was ongoing at the time of reporting; both flare cases led to study treatment discontinuation

• 1 new event was reported in a subject with gastrointestinal symptoms at baseline, suggestive of an undiagnosed active CD; the event resolved with therapy and did not cause study treatment discontinuation

2 cases of exacerbation of UC and 2 cases of new-onset UCwere reported over 52 weeks of secukinumab treatment2

1. van de Kerkhof PC et al. J Am Acad Dermatol. 2016;75(1):83-98. 2. Cosentyx [US package insert] 2015.

Integrated Safety of Ixekizumab in Patients With Moderate to Severe Psoriasis: Results From a Pooled Analysis of 7 Clinical Trials

This study was supported by Eli Lilly and Company.Presented at 2016 Fall Clinical Dermatology Conference; Las Vegas, Nevada; October 20-23, 2016.

Strober B, Papp KA, Leonardi CL, Bissonette R, Ferris L, Mrowietz U, Lebwohl M, Braun DK, Acharya N, Reich K

Crohn’s Disease

Incidence of reported CD was low and rates remained stable over time

Placebo Etanercept Ixekizumab Q4W

Ixekizumab Q2W

Ixekizumab Q12W

Ixekizumab Q4W

All Patients on Ixekizumab

0

2

4

6

IR9

5%

CI

n (%)N

0 (0.0)791

0 (0.0)739

1 (0.1)1161

1 (0.1)1167

0 (0.0)408

1 (0.2)416

9 (0.2)4209

IR (Patients With Event/100 PYs)

0.4 0.4 0.0 0.3 0.1

Fall Clinical Dermatology Conference; Las Vegas, Nevada; October 20-23, 2016.

0.0 0.0

12 Weeks(Phase 3 RCT)

12-60 Weeks(Phase 3 RCT)

Integrated Safety

Population (7 Trials)

Ulcerative Colitis

Incidence of UC was low and rates remained stable over time


Ixekizumab Q2W

Ixekizumab Q12W

Ixekizumab Q4W


0

2

4

6

IR9

5%

CI



Integrated Safety


n (%)N

0 (0.0)791

0 (0.0)739

0 (0.-)1161

2 (0.2)1167

2 (0.5)408

1 (0.2)416

10 (0.2)4209


0.0 0.0 0.00.7 0.7

0.3 0.2

Fall Clinical Dermatology Conference; Las Vegas, Nevada; October 20-23, 2016.

The patient was diagnosed and treated for breast cancer

After S/P chemo and radiation, in remission for the past

12 months

CASE 3: Ms. Morgan,56-Year-Old White Woman

15-year history of psoriasis

No arthritis

Psoriasis has gotten progressively worse; currently at 25% BSA

This photo is not the actual patient.S/P=status post. BSA=body surface area. Image source: https://en.wikipedia.org/wiki/Psoriasis.

Safety Surveillance for Ustekinumab and Other Psoriasis Treatments From PSOLAR

PSOLAR=Psoriasis Longitudinal Assessment and Registry. F/U=follow-up.Papp K et al. J Drugs Dermatol. 2015;14(7):706-714.

DiscontinuedPresumed lost to F/U

Patient choice Lost to F/U Other Death Site closed

No longer met criteria

4364received ustekinumab

1394received infliximab

4251received other biologics

2084received nonbiologics

Continuing in registry

Disposition of Patients Enrolled in PSOLAR (12,093 Patients Enrolled)

Ustekinumab*(N=4364)

12,472 PYs

Infliximab(N=1394)5176 PYs

Other Biologics(N=4251)

15,991 PYs

Nonbiologics(N=2084)6749 PYs

Total(N=12,093)40,388 PYs

nRate/

100 PYs nRate/

100 PYs nRate/

100 PYs nRate/

100 PYs nRate/

100 PYs

Malignancy† (excluding NMSC) 60 0.48 41 0.79 116 0.73 57 0.84 274 0.68

MACE† 40 0.32 17 0.33 45 0.28 32 0.47 134 0.33

Cardiovascular death 15 0.12 5 0.10 14 0.09 14 0.21 48 0.12

Nonfatal CVA 9 0.07 4 0.08 13 0.08 7 0.10 33 0.08

Nonfatal MI 16 0.13 8 0.15 21 0.13 13 0.19 58 0.14

Serious infections‡ 74 0.93 96 2.91 245 1.91 233 1.43 648 1.60

All-cause mortality† 51 0.41 21 0.41 67 0.42 46 0.68 185 0.46

Cardiovascular 15 0.12 5 0.10 14 0.09 14 0.21 48 0.12

Other 25 0.20 12 0.23 35 0.22 20 0.30 92 0.23

Unexplained death 11 0.09 4 0.08 18 0.11 12 0.18 45 0.11

Safety Surveillance for Ustekinumab and Other Psoriasis Treatments From PSOLAR (cont.)

PYs=patient-years. CVA=cerebrovascular accident.*Attribution rules for this analysis dictated that, after a patient was exposted to ustekinumab, subsequent adverse events of special interest were attributed to ustekinumab, regardless of past of future exposures and duration of other therapies. †‡Incidences for malignancy, MACE, and mortality were based on patients who were ever exposed to a given biologic therapy. ‡Incidences for serious infections were based on patients who were exposed to a given biologic therapy within 91 days of the event (40,389 total patient-years: 7944 for ustekinumab, 3301 for infliximab, 12,833 for other biologics, and 16,322 for nonbiologics.)Papp K et al. J Drugs Dermatol. 2015;14(7):706-714.

Number of Events and Cumulative Incidence Rates per 100 PYs of AEs of Special Interest

Secukinumab Malignancy Rates During the First 12 Weeks

During the first 12 weeks, the incidence of malignant or unspecified tumors was comparable in the secukinumab 300 mg, 150 mg, and placebo groups

• No event was reported in the etanercept group

n (%)

(95% CI)



Secukinumab 300 mg,150 mg, or Other Doses†


(n=323)Placebo(n=793)

Malignant or

unspecified tumors§

2 (0.17)

(0.03, 0.69)

4 (0.34)

(0.11, 0.93)

6 (0.21)

(0.08, 0.48)

0

(0, 1.5)

3 (0.4)

(0.1, 1.2)

NMSC|| 1 (0.09)

(0, 0.55)

2 (0.17)

(0.03, 0.68)

3 (0.10)

(0.03, 0.33)

0

(0, 1.5)

3 (0.4)

(0.1, 1.2)

Other malignancies§

(excluding NMSC||)

1 (0.09)

(0, 0.55)

2 (0.17)

(0.03, 0.68)

3 (0.10)

(0.03, 0.33)

0

(0, 1.5)

0

(0, 0.6)

CI=confidence interval. MedDRA=Medical Dictionary for Regulatory Activities. *Includes subjects from phase 3 studies only who were randomized to the specified secukinumab dose at the study. †Includes subjects from phase 2 and 3 studies who were randomized to any dose of secukinumab at the study start. ‡Etanercept data are from 1 pivotal phase 3 trial, FIXTURE. §Based on standardized MedDRA query. ||Based on narrow Novartis MedDRA query.van de Kerkhof PC et al. J Am Acad Dermatol. 2016;75(1):83-98.

Initial 12-Week Treatment Period (Baseline to Week 12)

Secukinumab Exposure-Adjusted IRof Malignancy

Over 52 weeks, the exposure-adjusted IR of malignant or unspecified tumors was comparable in the secukinumab 300 mg, 150 mg, and etanercept groups

• For malignant or unspecified skin tumors, the exposure-adjusted IR (per 100 subject-years) was also comparable in the secukinumab 300 mg (0.60), 150 mg (0.70), and etanercept (0.34) treatment groups

The exposure-adjusted IR of NMSC was comparable in the secukinumab 300 mg and 150 mg groups

With NMSC cases excluded, the exposure-adjusted IR of malignant or unspecified tumors was comparable in the secukinumab 300 mg and 150 mg groups and lower than that in the etanercept group

n (IR per 100 Subject-Years)

(95% CI)



Secukinumab 300 mg, 150 mg,or Other Doses†


(n=323)

Malignant or unspecified tumor§ 9 (0.77)

(0.35, 1.46)

11 (0.97)

(0.48, 1.73)

26 (0.96)

(0.63, 1.40)

2 (0.68)

(0.08, 2.47)

NMSC|| 5 (0.43)

(0.14, 0.99)

7 (0.61)

(0.25, 1.27)

13 (0.48)

(0.25, 0.82)

0

(0, 1.26)

Other malignanciesd (excluding NMSC||)4 (0.34)

(0.09, 0.87)

4 (0.35)

(0.10, 0.90)

13 (0.48)

(0.25, 0.82)

2 (0.68)

(0.08, 2.47)

Entire Treatment Period (Baseline to Week 52)

*Includes subjects from phase 3 studies only who were randomized to the specified secukinumab dose at the study start and subjects on placebo who were rerandomizedto secukinumab at Week 12. †Includes subjects from phase 2 and 3 studies who were randomized to any dose of secukinumab at the study start and subjects on placebo who were rerandomized to secukinumab at Week 12. ‡Etanercept data are from 1 pivotal phase 3 trial, FIXTURE. §Based on standardized MedDRA query. ||Based on narrow Novartis MedDRA query. van de Kerkhof PC et al. J Am Acad Dermatol. 2016;75(1):83-98.

Integrated Safety of Ixekizumab in Patients With Moderate to Severe Psoriasis: Results From a Pooled Analysis of 7 Clinical Trials

This study was supported by Eli Lilly and Company.Presented at 2016 Fall Clinical Dermatology Conference; Las Vegas, Nevada; October 20-23, 2016.

Strober B, Papp KA, Leonardi CL, Bissonette R, Ferris L, Mrowietz U, Lebwohl M, Braun DK, Acharya N, Reich K.

Integrated Safety of Ixekizumab in Patients With Moderate to Severe Psoriasis, Pooled Analysis of 7 Clinical Trials: Malignancies Excluding NMSC

Malignancies excluding NMSC were uncommon and balanced between ixekizumab and placebo


Ixekizumab Q2W

Ixekizumab Q12W

Ixekizumab Q4W


0

2

4

6

IR9

5%

CI



Integrated Safety


n (%)N

1 (0.1)791

1 (0.1)739

2 (0.2)1161

1 (0.1)1167

2 (0.5)408

0 (0.0)416

33 (0.8)4209


IR=incidence rate (exposure-adjusted) per 100 PYs. Q2W=80 mg ixekizumab every 2 weeks. IXE Q4W=80 mg ixekizumab every 4 weeks. Q12W=80 mg ixekizumab every 12 weeks. RCT=randomized controlled trial.Fall Clinical Dermatology Conference; Las Vegas, Nevada; October 20-23, 2016.

0.6 0.60.8

0.40.7

0.0 0.5

Influence of Anti-TNF Therapy on CI in Patients With RA Who Have Had a Prior Malignancy

• Results from the British Society for Rheumatology Biologics Register

• Study evaluated patients with RA and malignancy treated with either a biologic agent or a nonbiologic control

• 177 patients treated with biologics vs 117 treated with nonbiologics, all with a history of malignancy

• Results demonstrated no increased risk of new primary, recurrent, or metastatic malignancies in the biologic arm (IR ratio 0.58; 95% CI 0.23-1.43)

RA=rheumatoid arthritis. DMARD=disease-modifying antirheumatic drugs.Dixon WG et al. Arthritis Care Res (Hoboken). 2010;62(6):755-763.

Influence of Anti-TNF Therapy on CI in Patients With RA Who Have Had a Prior Malignancy (cont.)

% C

um

ula

tive Incid

ence

Cumulative Incidence of Malignancy in Patients With Prior Malignancy by Nelson-Aalen Plot

0 1 2 3

0

12

14

16

4

6

8

10

2

4

Years Since Registration

Results From the British Society for Rheumatology Biologics Register.Dixon WG et al. Arthritis Care Res (Hoboken). 2010;62(6):755-763.

DMARD

Anti-TNF

Risk of Incident or Recurrent Malignancies Among Patients With RA Exposed to Biologic Therapy in the German Biologics Register

• Results from the German Rheumatoid Arthritis Observation of Biologic Therapy Register (RABBIT)

• The study analyzed whether biologic use causes increased risk of new or recurrent malignancies

• This study found no significant increase in the risk of recurrence in patients with a previous history of cancer exposed to biologics compared to nonbiologics (1.4; 95% CI 0.5-5.5)

Strangfeld A et al. Arthritis Res Ther. 2010;12(1):R5.

Observed Numbers of Cancers and Expected Numbers From the General Population, Standardized by Age and Sex

Total number of malignancies

60 0 6040 20 20 40

15 0 1510 5 5 10

58.7 29.444.0 30.0

Reproductive organs—males

Reproductive organs—females3.0 3.0

6.0 3.0

3.0 1.04.9 2.4

Pancreatic cancer1.0 5.0

1.5 0.8

Non-Hodgkin’s lymphoma 1.05.01.9 0.9

Malignant melanoma

Lung cancer

Breast cancer

3.0 0.02.1 1.0

7.05.7 2.8

6.0

8.013.9 6.8

3.0 Expected

Observed

Strangfeld A et al. Arthritis Res Ther. 2010;12(1):R5.

Risk of Incident or Recurrent Malignancies Among Patients With RA Exposed to Biologic Therapy in the German Biologics Register (cont.)

Anti-TNFα Controls

Question and Answer Session

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