Ron J. Feldman, MD, PhD Assistant Professor Dept. of Dermatology Emory University

Transkript

1 Ron J. Feldman, MD, PhD Assistant Professor Dept. of Dermatology Emory University

2 Outline Overview of Pemphigoid Diseases Current Treatments B-Cell Mediated Autoimmune Diseases Rituximab Therapy

3 Treatments for Pemphigoid Steroids Topical Oral Prednisone Other immune suppressing medications Dapsone Methotrexate Mycophenolate Azathioprine Intravenous immunoglobulin Need for Improved Therapies

4 Autoimmune Disease: Antibodies Bind to Skin Proteins Upper Layer of Skin = Epidermis Lower Layer of Skin = Dermis

5 Pemphigoid Diseases Bullous Pemphigoid Antibody Attack of Collagen XVII Ujiie H, Journal of Dermatological Science, 78, 2015

6 Inappropriate Signal Origin of the Autoantibody? Qiu J et al, Biosensors 8(3), 2018

7 Similar Autoimmune Mechanism as Pemphigus? J. Clin. Invest. 116: (2006)

8 B Cell Depletion Therapy B-Cell Mediated Diseases: Deplete the B Cells??

9 Rituximab

10 Rituximab distribution 6 hours post infusion Dermatomyositis RA Sjogren s Behcet s Sarcoidosis Malviya G, et al, Mol Imaging Biol, 2012; 14(5):

11 Rituximab: How Does it Work?

12 How Does Rituximab Work? Nagel A et al, Journal of Investigative Dermatology 129 (2), 2009

13 Balance of B Cells Sanz I et al, B cells and immunological tolerance, JID 129, , 2009

14 Rituximab Is it effective? Is it safe? How many treatments will I need? Is it expensive; will my insurance cover?

15 Rituximab Is it Effective? Way back in 2002 First published case report in bullous pemphigoid Bullous pemphigoid Two large case series 11 patients treated with rituximab and IVIG all developed remission (2 required repeat rituximab infusions), Ahmed AR et al, Journal of the American Academy of Dermatology 74: 700-8, 2016 Study comparing rituximab therapy (13 patients) versus steroids alone (19 patients) in bullous pemphigoid: Cho et al British Journal of Dermatology, 2015: 90% of patients achieved complete remission in rituximab group versus 53% in steroids along group

16 Rituximab Is it Effective? Case series in difficult to treat MMP patients 88% of patients 22/25 patients achieved remission; Le Roux-Villet C et al, Archives of Dermatology, 147 (7) % of patients in rituximab group compared to 40% in the conventional group achieved disease control; Maley A, et al, Journal of the American Academy of Dermatology, 74: , 2016 Encouraging results in MMP

17 Rituximab Is it Safe? Risk for Infection? Study comparing rituximab therapy (13 patients) versus steroids alone (19 patients) in bullous pemphigoid: Cho et al British Journal of Dermatology, 2015 Infection risk was lower 31% versus 53% (not significant) Urinary tract infections and pneumonia main infections Mortality rates? Mortality rate much lower in rituximab group, 15% versus 37% (not significant)

18 Rituximab How many Treatments? Bullous Pemphigoid 11 patients treated with rituximab and IVIG all developed remission--2 required repeat rituximab infusions, Ahmed AR et al, Journal of the American Academy of Dermatology 74: 700-8, 2016 Mucous Membrane Pemphigoid At Emory, 10 of 24 patients experienced a relapse Maley A et al, Journal of the American Academy of Dermatology; 74: 835, 2016 Repeated rituximab cycles in 5 patients with improvement Two Rituximab cycles were given to 16 of 25 patients; 12 of these patients went into remission. Le Roux-Villet C et al, Archives of Dermatology, 147 (7) 2011 Anecdotally, some patients require maintenance therapy at 6-12 months

19 Rituximab Is it Expensive? Rituximab infusions for Pemphigoid is off label in the US for not approved by the FDA Infusion costs are still substantial--each infusion at Emory is billed at $16,000 More information we can provide insurance companies better chance to get coverage Always check with your insurance plan and billing departments to clarify the real cost for you

20 Conclusion Rituximab demonstrates efficacy in Pemphigoid diseases How many cycles you will need is not clear and is individual dependent at this point Safety concerns are similar to conventional immune suppressing medications Need more data, clinical trials to clarify these issues

21 The End Questions? Thank you IPPF! Please go by our booth and see Taryn for Quality of Life Research Study