Psoriasis Patients with: Integrating New Psoriasis Therapies Into Your Practice

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1 Integrating New Psoriasis Therapies Into Your Practice Mark Lebwohl, MD Sol and Clara Kest Professor And Chairman Department of Dermatology The Mount Sinai School of Medicine Psoriasis Patients with: Psoriatic arthritis Palmoplantar psoriasis History of multiple SCC s Longterm methotrexate therapy in psoriatic arthritis: clinical and radiological outcome. Abu-Shakra M, et al. J Rheumatol 995 Feb; 22(2):24-5. Mtx does not prevent joint damage on x-ray. Adalimumab Percent ACR Response at Weeks 2 and 24 Percent of Patients Placebo Adalimumab Placebo Adalimumab n=62 n=5 n=62 n=5 57 Week 2 Week ACR2 ACR5 ACR7 All results p<. placebo vs adalimumab Mease P, et al. Presented at the 68 th Annual Scientific Meeting of the American College of Rheumatology, October 9, 24; San Antonio, Texas. Change in mtss Mean Change in mtss at Week 24 Placebo Adalimumab Weeks N Baseline Mean change Placebo Adalimumab *** Effect of certolizumab pegol on signs and symptoms in patients with psoriatic arthritis: 24-week results of a Phase 3 double-blind randomised placebo-controlled study (RAPID-PsA) Mease PJ, Fleischmann R, Deodhar AA, Wollenhaupt J, Khraishi M, Kielar D, Woltering F, Stach C, Hoepken B, Arledge T, van der Heijde D. Ann Rheum Dis. 24;73: Source: Mease, et al. Presented at: EULAR Congress; June 8-25; Vienna, Austria. ***p. vs placebo for ranked ANCOVA

2 Treatment of psoriatic arthritis in a phase 3 randomised, placebocontrolled trial with apremilast, an oral phosphodiesterase 4 inhibitor. Kavanaugh A, et al Ann Rheum Dis. 24;73:2-6. PSUMMIT Study Group. Efficacy and safety of ustekinumab in patients with active psoriatic arthritis: year results of the phase 3, multicentre, double-blind, placebo-controlled PSUMMIT trial. McInnes IB, Kavanaugh A, Gottlieb AB, Puig L, Rahman P, Ritchlin C, Brodmerkel C, Li S, Wang Y, Mendelsohn AM, Doyle MK; Lancet. 23;382(9894):78-9. Brodalumab, an anti-il7ra monoclonal antibody, in psoriatic arthritis. Mease PJ, Genovese MC, Greenwald MW, Ritchlin CT, Beaulieu AD, Deodhar A, Newmark R, Feng J, Erondu N, Nirula A. N Engl J Med. 24 Jun 2;37(24): Secukinumab improves patient-reported outcomes in subjects with active psoriatic arthritis: results from a randomised phase III trial (FUTURE ). Strand V, et al FUTURE study group. Ann Rheum Dis. 26 [Epub ahead of print] An investigator-initiated, open-label study evaluating the efficacy and safety of UST in patients with moderate-tosevere palmar/plantar psoriasis 24 subjects with palmar/plantar psoriasis with PGA 3 treated with FDA-approved dose of UST using weight-based dosing Report of 2/24 subjects, in 45-mg dose, 9 in 9-mg dose. Mean weight of subjects not reported Investigator-initiated, open-label trial of ustekinumab for the treatment of moderate-tosevere palmoplantar psoriasis. J Dermatolog Treat. 22 May 8. [Epub ahead of print] Au SC, Goldminz AM, Kim N, Dumont N, Michelon M, Volf E, Hession M, Lizzul PF, Andrews ID, Kerensky T, Wang A, Yaniv S, Gottlieb AB. 7/2 clear (9 mg:6/9; 45mg:/) 2/2 >2point PGA improvement Shimrat Y, et al. AAD 22: P4733; Study sponsored by Centocor 2

3 at least one point of PGA at week 2 Safety and efficacy of Adalimumab in the treatment of moderate to severe palmo-plantar psoriasis: an open label study. Richetta AG, et al Clin Ter. 22;63:e6-6. improvement (>point) PGA: 6/ >5% improvement 5/ 4/ clear Clinical and patient-reported improvements of hand and/or foot psoriasis with ADA 4 mg qow: Subanalysis of REACH Subanalysis of REACH study looking at elements of erythema, scaling, induration and fissuring (ESIF) score along with DLQI % Patients Achieving Change from Baseline in ESIF Score of > Patients achieving a change from baseline in ESIF score of >4.98 Week 6 Week 28 Menter A, et al. AAD 22: P56; Study sponsored by Abbott Laboratories PBO ADA Non-responder imputation. ESIF: Erythema, scaling, induration, fissuring. Successful treatment of hand and foot psoriasis with infliximab. Di Lernia V, Guareschi E. Dermatol Online J. 2 ;6:8. Severe psoriasis pustulosa palmaris et plantaris (Barber-Königsbeck) treated successfully with soluble tumour necrosis factor receptor fusion protein (etanercept). Kasche A, et al J Eur Acad Dermatol Venereol.27;2: Apremilast, an oral phosphodiesterase-4 inhibitor, in the treatment of palmoplantar psoriasis: Results of a pooled analysis from phase II PSOR-5 and phase III Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis (ESTEEM) clinical trials in patients with moderate to severe psoriasis. Bissonnette R, et al. J Am Acad Dermatol. 26 [Epub ahead of print] PPPGA or Achievement at Week 6 in Patients With Baseline PPPGA Patients Achieving PPPGA or (%) * Placebo Apremilast 3 mg BID * 65.4 n/m = 2/ 6/ 8/26 22/57 5/6 7/2 9 6 PSOR-5 ESTEEM ESTEEM 2 *P<.5 vs. placebo. Includes patients with Palmoplantar Psoriasis Physician Global Assessment (PPPGA) 3, indicating moderate or severe palmoplantar psoriasis, at baseline; all data are last observation carried forward. n/m=number of patients with response/number of patients with sufficient data for evaluation. Secukinumab improves hand, foot and nail lesions in moderate-to-severe plaque psoriasis: subanalysis of a randomized, double-blind, placebo-controlled, regimen-finding phase 2 trial. Paul C, Reich K, Gottlieb AB, Mrowietz U, Philipp S, Nakayama J, Harfst E, Guettner A, Papavassilis C; CAIN457A22 study group. JEur Acad Dermatol Venereol. 24;28:

4 Hands and feet IGA / response rates Full analysis set subgroup of patients with hands and/or feet psoriasis dosing Patients achieving hands and feet IGA / response rate (%) *p=.74 vs placebo 3x 5 mg 3x 75 mg 3x 25 mg x 25 mg Placebo * 7.4% (5/7) 2.% (2/) 2.% (/5 ) 6.7% (/6) Weeks 3x 25 mg; for both 3x 75 mg and placebo 43 y.o. WF 5% Psoriasis Failed UVB PUVA x 7 yrs 4 therapies 5 SCC s, 8 in past months Highest response after 2 weeks seen in 3x 5 mg arm Sigurgeirsson B, et al. EADV 22: P945; Study sponsored by Novartis Options: ) More PUVA 2) Cyclosporine 3) Methotrexate 4) Acitretin 5) Apremilast 6) TNF-α blocker 7) Ustekinumab 8) Secukinumab, ixekizumab, brodalumab Posttransplant lymphoproliferative disorders after renal transplantation in the United States in era of modern immunosuppression. Transplantation. 25;8(9): Caillard S, et al.4% develop nonhodgkins lymphoma Risk of Nonmelanoma Skin Cancer Associated With the Use of Immunosuppressant and Biologic Agents in Patients With a History of Autoimmune Disease and Nonmelanoma Skin Cancer. Scott FI et al JAMA Dermatol. 26;52: individuals with RA or IBD mtx + other medications 2 nd NMSC HR.6 (CI, ) Adjusted for other medications, mtx >yr NMSC HR.24 (CI,.4-.48) anti-tnf NMSC HR.49 (CI, trials analyzed RA, PsA, JRA, PsO, AS 3,926 ETN subjects; 7,656 patient-years Presented at EULAR 28 Malignancies in Patients Receiving Etanercept Across Indications AB Gottlieb, KB Gordon, EH Giannini, PJ Mease, et al J Drugs Dermatol. 2;:

5 Results SIRs (95% CIs) of Squamous Cell Carcinomas in Subjects Receiving Etanercept in Clinical Trials: High Sun Exposure Comparison SIRs for SCCs: High Sun Exposure Comparison (Harris 2) Total Results SIRs (95% CIs) of Squamous Cell Carcinomas in Subjects Receiving Etanercept in Clinical Trials: Low Sun Exposure Comparison SIRs for SCCs: Low Sun Exposure Comparison (Gray 997) Total RA JRA* PsA* AS* PsO Menu *No malignancies reported. May be used in response to the request for this scientific information. RA JRA* PsA* AS* PsO Menu *No malignancies reported. May be used in response to the request for this scientific information. Adalimumab: long-term safety in 23,458 patients from global clinical trials in rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis and Crohn s disease G. Burmester, Panaccione R, Gordon KB, McIlraith MJ, Lacerda AP Ann Rheum Dis. 22 Jul 6. Epub ahead of print 5

6 Prevention of Skin Cancer and Reduction of Keratotic Skin Lesions During Acitretin Therapy in Renal Transplant Recipients: A Double- Blind, Placebo-Controlled Study. Bouwes Bavinck JN, Tieban LM, Van der Woude FJ, et al. J Clin Oncol 3:933-38,995. Acitretin 3 mg/day vs. placebo 2/9 2 SCC s vs. 9/9 8 SCC s Multiple squamous cell carcinomas in a psoriatic patient following highdose photochemotherapy and cyclosporin treatment: response to long-tern acitretin maintenance. Van der Kerkhof PC, de Rooij MJ. Br J Dermatol 997 Feb;36(2): Ustekinumab Psoriasis Safety Databases: Duration of Patient Exposure* Evaluated in 2 and 2 Analyses The 2 Analyses included a total of 37 patients with 8998 PY of follow-up; 47.5% of patients were treated for at least 4 years and 26.9% treated for 5 years (median follow-up was 3.2 years) Cumulative Rates of NMSC Through 5 Years of Follow-up 47 patients reported NMSCs (3 patients reported both SCC and BCC) 4 had BCC (2 on 45 mg and 9 on 9 mg) had SCC (5 on 45 mg and 5 on 9 mg) Number of Patients Analyses (n=37, PY of follow-up = 679) 2 Analyses (n=37, PY of follow-up = 8998) year 2 years 3 years 4 years 4.5 years 5 years Duration of UST Exposure* Rate per PY (95% CI) (.4, 4.9).49 (., 2.75).98 (.2, 3.55).74 (.5, 2.6) BCC:SCC = 3:.7 (.43,.9).53 (.33,.82).6 (.43,.82) Controlled Period 2 Analyses 2 Analyses Placebo UST 45 mg UST 9 mg UST Combined BCC:SCC = 4:.64 (.4,.95).44 (.28,.66).52 (.39,.7) n PY f/u # patients *PBO subjects crossed-over to UST at Week 2, therefore they would only be captured in categories of 4 years and 4.5 years of exposure Papp K., et al. EADV 22. P965. ACCEPT data were not included in the Controlled Period rates since it did not include a placebo comparator. For PHOENIX 2, patients who were dose adjusted from 45 mg to 9 mg were switched to the corresponding column following dose adjustment. Cumulative Rates of Other Malignancies Through 5 Years of Follow-up Rate per PY (95% CI) (.37,.89) (.42,.87) (.45,.78) (.37,.) (.39,.9) (.45,.84).25 (., 3.5) (., 2.75). (.,.37) (.,.47). Controlled Period 2 Analyses 2 Analyses n 732 PY f/u # patients Placebo UST 9 mg UST Combined UST 45 mg ACCEPT data were not included in the Controlled Period rates since it did not include a placebo comparator. PHOENIX 2 patients who were dose adjusted from 45 mg to 9 mg were switched to the corresponding column following dose adjustment. IL-7 Mediated Inflammation Promotes Tumor Growth and Progression in the Skin D. He, et al PLoS ONE 22; 7: -9 IL-23 IL-7 tumor growth Could blocking IL-7 be protective against cancer? 6

7 Options: Reasons to Become a Registry Investigator ) More PUVA 2) Cyclosporine 3) Methotrexate 4) Acitretin 5) Apremilast 6) TNF-α blocker 7) Ustekinumab 8) Secukinumab, ixekizumab, brodalumab Contribute to education/clinical knowledge of the psoriasis community Opportunity to establish a database of your patient population Academic recognition and publication opportunities Supplement existing insurance fee schedules Site compensation is $4 (including $2 for patient) per Enrollment visit and $3 (including $2 for patient) per biannual Follow Up visit Become a Registry Research Investigator If you are interested in participating in the Psoriasis Registry as a research investigator, please psoriasis@corrona.org or visit or call