Michael P. Heffernan, M.D San Luis Dermatology & Laser Clinic Director, US Probity Medical Research

Transcription

1 Michael P. Heffernan, M.D San Luis Dermatology & Laser Clinic Director, US Probity Medical Research

2 DISCLOSURES Consultant, Speaker, Investigator: Abbvie, Amgen, Brickell Biotech, Dermavant, DS Biopharma, Eli Lilly & Co., Foamix, Incyte, Janssen, Merck/Serono, Novartis Employee/Stockholder(ended Sept 2014): Eli Lilly & Co.

3 Probity Medical Research International Consortium of Dermatology Researchers Adding research sites all across the US

4 Objectives Understand how new biologic therapies will dramatically change dermatology. Understand how the MOA of the biologic determines which Derm diseases will be successfully treated

5 ARS: Which Disease has the Highest Need for a Biologic? 1. Severe Atopic Dermatitis 2. Hidradenitis Suppurativa 3. Plaque Psoriasis 4. Pemphigus Vulgaris 5. Pyoderma Gangrenosa 6. Chronic Urticaria

6 Our Current Biologics Anti-TNF Receptor: Etanercept Antibody: Adalimumab, Infliximab, Certolizumab Anti-IL-12/23: Ustekinumab Anti-IL-17: Secukinumab, Ixekizumab Anti-IL-17RA: Brodalumab Anti-IL-23: Guselkumab, Tildrakizumab IL-1 RA: Anakinra Anti-IL-1B: Canakinumab Anti-IgE: Omalizumab Anti-CD20: Rituximab Anti-IL-4/13: Dupilumab

7 Tumor Necrosis Factor(TNF) TNF has myriad upstream and effector roles in TH1 inflammation Receptor binds free TNF Antibodies bind free and bound TNF Both approved for PSO, PSA, RA, AS Antibodies approved for Crohns, UC and Adalimumab is approved for HS

8 TNF Mediated Derm Diseases FDA Approved: Psoriasis Hidradenitis Suppurativa Off Label: Sarcoid GA/NLD Pyoderma Gangrenosa TEN Pityriasis Rubra Pilaris

9 Sarcoid Effective: Infliximab, Adalimumab Ineffective: Etanercept, Ustekinumab, Golimumab Drent M, Cremers JP, Jansen TL, et al. Practical eminence and experience-based recommendations for use of TNF-alpha inhibitors in sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2014;31(2):

10 Sarcoid (Cont.) Rossman MD, Newman LS, Baughman RP, et al. A double-blind, randomized, placebocontrolled trial of infliximab in patients with active pulmonary sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2006;23: Kamphuis LS, Lam-Tse WK, Dik WA, et al. Efficacy of adalimumab in chronically active and symptomatic patients with sarcoidosis. Am J Respir Crit Care Med. 2011;184(10):

11 Sarcoid (cont.) Judson MA, Baughman RP, Costabel U, et al. Safety and efficacy of ustekinumab or golimumab in patients with chronic sarcoidosis. Eur Respir J. 2014;44: Pariser RJ, Paul J, Hirano S, et al. A double-blind, randomized, placebocontrolled trial of adalimumab in the treatment of cutaneous sarcoidosis. J Am Acad Dermatol. 2013;68(5): (10 cases/ 6 placebo)

12 Granuloma Annulare Effective: Adalimumab, Infliximab Ineffective: Etanercept Min M, Lebwohl M. Treatment of recalcitrant granuloma annulare (GA) with adalimumab: A single-center, observational study. JAAD: 74(1) (7 cases)

13 Hidradenitis Suppurativa FDA Approved: Adalimumab Effective: Infliximab, Adalimumab Possible: Ustekinumab, Anakinra Ineffective: Etanercept Grant A, Gonzalez T, Montgomery MO, et al. : Infliximab therapy for patients with moderate to severe hidradenitis suppurativa: a randomized, double-blind, placebo-controlled crossover trial. J Am Acad Dermatol. 2010;62(2): Blok JL, Li K, Brodmerkel C, et al. : Ustekinumab in hidradenitis suppurativa: clinical results and a search for potential biomarkers in serum. Br J Dermatol. 2016;174(4): (17 cases)

14 Pyoderma Gangrenosa Effective: Infliximab(104), Adalimumab(15) Maybe: Ustekinumab (3), Canakinumab(6) Ineffective: Etanercept (7) The Future: anti-il-17??? Quist, S. R. and Kraas, L. (2017), Treatment options for pyoderma gangrenosum. JDDG: Journal der Deutschen Dermatologischen Gesellschaft, 15:

15 Toxic Epidermal Necrolysis Thalidomide trial worsened TEN Infliximab: 15 Case Reports 14/15 survive Etanercept: 12 Case Reports 11/12 survive

16 Pityriasis Rubra Pilaris Effective: Adalimumab, Infliximab, Ustekinumab Petrof G, Almaani N, Archer CB, Griffiths WAD, Smith CH. A systematic review of the literature on the treatment of pityriasis rubra pilaris type 1 with TNF-antagonists. J Eur Acad Dermatol Venereol. 2013;27:e131 e135. (15 Cases) Chowdhary M, Davila U, Cohen DJ. Ustekinumab as an alternative treatment option for chronic pityriasis rubra pilaris. Case Rep Dermatol. 2015;7(1): (4 cases, 6 since)

17 B Cell Derm Diseases Pemphigus Vulgaris Pemphigus Foliaceous Paraneoplastic Pemphigus Bullous Pemphigoid Mucous Membrane Pemphigoid Epidermolyis Bullosa Acquisita Vasculitis

18 Anti CD20: Rituximab CD20 is present on mature B cells. Anti- CD20 leads to sustained reduction in mature B cells FDA approved for Lymphoma, Rheumatoid Arthritis

19 Rituximab for Pemphigus Lymphoma: 375mg/m2 weekly x4 RA Protocol: 1000mg x 2 CR: 66.6%(L) vs. 75%(R) PR: 12.78%(L) vs %(R) Relapse: 22.78%(L) vs %(R) Ser. Infxn: 3.9%(L) vs. 15.2% (R) Mortality: 2.2% (L) vs. 1.1% (R) Dermatol Ther (Heidelb) Dec;2(1):17

20 Rituximab for Pemphigus 578 patients 76% Complete Response 5.8mos mean time to remission 40% Relapse Rate 3.3% Serious Adverse Events Acta Derm Venereol Apr 17

21 Key Takeaways We have several Biologic Medications that target specific parts of the immune system In addition to the FDA approved indications (Psoriasis and HS), the anti-tnf antibodies (Adalimumab and Infliximab) work well for Pyoderma Gangrenosa, PRP, Granuloma Annulare and Cutaneous Sarcoid Rituximab targets B cells and is the first line agent for pemphigus vulgaris and other AIBD s

22 The Future Biosimilars The Payor Decides Everything!!! Ask me about Probity