PracticeUpdate Dermatology Best of 2018

EDITOR’S PICKS 13

Maintenance of Skin Clearance With Ixekizumab Treatment of Psoriasis Journal of the American Academy of Dermatology Take-home message

• This study reports on the long-term efficacy and safety of ixekizumab in patients with psoriasis treated for 3 years in the UNCOVER-3 study. Of the 385 participants originally randomized to receive ixekizumab every 2 weeks for 12 weeks and then every 4 weeks thereafter, 77.9% completed the total of 156 weeks, among whom the percentage with PASI 75, 90, and 100 at week 156 were 80.5%, 66.0%, and 45.1%, respectively. Clinical responses were also maintained by participants with nail, scalp, and palmoplantar involvement of their psoriatic disease at baseline. Infections, including viral and upper respiratory tract infections, were the most commonly reported adverse events reported over the course of the study. • Ixekizumab demonstrated sustained clinical efficacy over 3 years, with a safety profile consistent with that reported with other psoriasis treatments. Jeffrey F. Scott MD

" The current paper now allows us to also say that the response

COMMENT By Mark G. Lebwohl MD and George Han MD, PhD W hen a drug is first approved after phase III time-limited stud- ies, patients and physicians

Abstract BACKGROUND Psoriasis, a chronic disease, may require long-term treatment. Ixekizumab, a high-affinity monoclonal antibody that selec- tively targets interleukin-17A, is an approved therapy for patients with moderate-to-severe plaque psoriasis. OBJECTIVE To evaluate efficacy and safety of ixekizumab through 156 weeks from the UNCOVER-3 study in patients who received the recommended dose regimen [160 mg at Week 0, 80 mg every 2 weeks (IXE Q2W) to Week 12, and 80 mg every 4 weeks (IXE Q4W) thereafter. METHODS Patients randomized to IXE Q2W, IXE Q4W, etanercept twice weekly, or placebo were switched to IXE Q4W during long-term extension period. Efficacy data were summarized using as-observed, multiple imputation (MI), and mod- ified nonresponder imputation (mNRI) methods. RESULTS At Week 156, response rates were 80.5%, 66.0%, and 45.1% for PASI 75, 90 and 100 using mNRI method, respectively, and 97.2% and 86.2 for PASI 75 using as-observed and MI methods, respectively. Similar response rates were observed in patients with baseline scalp, nail, or palmoplantar involvement. No new safety signals were identi ed through Year 3. LIMITATIONS No placebo or active comparison after Week 12. CONCLUSION Ixekizumab sustained high responses with clearance of skin and nail lesions, with no new safety concerns through 3 years. Maintenance of Skin Clearance With Ixeki- zumab Treatment of Psoriasis: Three-Year Results From the UNCOVER-3 Study. J AmAcad Dermatol 2018 May 24;[EPub Ahead of Print], C Leonardi, C Maari, S Philipp, et al. www.practiceupdate.com/c/69091 is durable and that the safety of the drug does not appear to change with long-term use. "

and 45.1% of patients achieved PASI 90 and PASI 100, respectively, using the mod- ified non-responder imputation analysis. The observation that only 3% of patients discontinued because of lack of effi- cacy is further evidence of the durability of response seen with this drug. Equally impressive was the durability of response for scalp and nails; but, perhaps most impressive, was the improvement in pal- moplantar psoriasis. The PP PASI 100 rate by modified non-responder imputation at week 156 was 60.5%. Using other statisti- cal analyses such as “as observed,” 84.7% of patients achieved PP PASI 100 at week 156, a response rate never seen before for palmoplantar psoriasis. It should be pointed out that this response rate might not be seen in patients with predomi- nant palmoplantar psoriasis in contrast to palmoplantar lesions in patients with pre- dominant generalized plaque psoriasis. In summary, previous studies have shown the high degrees of efficacy and the speed of response achieved by ixeki- zumab. The current paper now allows us to also say that the response is durable and that the safety of the drug does not appear to change with long-term use.

naturally ask a number of questions. The first and most important questions include the following: 1) Will the drug continue to be safe with long-term use; and 2) will the drug continue to be effective with long- term use? The paper by Leonardi et al answers both of those questions with a resounding “yes.” Rare side effects may not become evident until a drug has been used in thousands of patients for many years, but it is comforting to know that over 1000 patients have been followed for 3 years without the emergence of any new unexpected side effects. When fol- lowing 1274 patients for 3 years, adverse events certainly occur, but the frequency of malignancies, respiratory infections, and cerebrocardiovascular events were not greater than one would expect in the general population. Candida infec- tions, which were noted in early trials of ixekizumab, certainly did occur in 4.6% of patients, and there were 4 patients (0.3%) who developed Crohn’s disease; how- ever, these had been noted in early trials of all of the drugs that block IL-17. And patients born with mutations in IL-17 or its receptor develop chronic mucocuta- neous candidiasis, so the development of monilial infections was anticipated. The durability of response in patients treated with the approved dosing of ixeki- zumab was particularly noteworthy. Using a rigorous modified non-responder impu- tation method, at 3 years 80.5% of patients had maintained PASI 75. Overall, 66.0%

Dr. Lebwohl is Professor and Chairman of the Department of Dermatology at Mount Sinai School of Medicine in New York.

Dr. Han is Chair of the Department of Dermatology at Mount Sinai Beth Israel in New York.

VOL. 2 • NO. 4 • 2018