Efficacy, Safety, and Patient-Reported Outcomes in Patients with Moderate-to-Severe Plaque Psoriasis Treated with Brodalumab for 5 Years in a Long-Term, Open-Label, Phase II Study

Abstract

Background: Chronic inflammatory diseases such as psoriasis require treatment options that maintain efficacy and tolerability during extended treatment.

Objective: The aim of the study was to assess the long-term efficacy and safety of brodalumab, a fully human anti-interleukin-17 receptor A monoclonal antibody, in patients with moderate-to-severe plaque psoriasis.

Methods: Patients who completed a 12-week, phase II, dose-ranging clinical trial received brodalumab 210 mg every 2 weeks in an open-label extension study. Efficacy was assessed by static physician's global assessment (sPGA) and psoriasis area and severity index (PASI). Quality of life, assessed by dermatology life quality index (DLQI), and safety were also evaluated.

Results: Overall, 181 patients received brodalumab for a median of 264 weeks. Brodalumab treatment resulted in rapid improvements in sPGA, PASI, and DLQI that were maintained through week 264. Achieving PASI 90 to < 100 or PASI 100 at weeks 12, 240, and 264 was associated with greater likelihood for DLQI 0 or 1 compared with achieving PASI 75 to < 90. Over 5 years, one adverse event of suicidal ideation was reported, no suicides occurred, and no new safety signals emerged.

Conclusions: Brodalumab demonstrated skin clearance and improved quality of life, with an acceptable safety profile, throughout 5 years of treatment. CLINICALTRIALS.

Gov identifier: NCT01101100.

Conflict of interest statement

Mark G. Lebwohl is an employee of Mount Sinai, which receives research funds from AbbVie, Boehringer Ingelheim, Bausch Health, Celgene, Eli Lilly, Incyte, Janssen/Johnson & Johnson, Leo, Medimmune/Astra Zeneca, Novartis, Pfizer, Sciderm, UCB, and Vidac, and is also a consultant for Allergan, Aqua, Arcutis, Boehringer-Ingelheim, Leo, Menlo, and Promius. Andrew Blauvelt has served as a scientific adviser and/or clinical study investigator for AbbVie, Aclaris, Akros, Allergan, Almirall, Amgen, Arena, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dermavant, Dermira, Eli Lilly, FLX Bio, Galderma, Genentech/Roche, GlaxoSmithKline, Janssen, Leo, Meiji, Merck Sharp & Dohme, Novartis, Pfizer, Purdue Pharma, Regeneron, Revance, Sandoz, Sanofi Genzyme, Sienna Pharmaceuticals, Sun Pharma, UCB, and Vidac and as a paid speaker for AbbVie, Regeneron, and Sanofi Genzyme. Alan Menter has received compensation from or served as an investigator, consultant, advisory board member, or speaker for AbbVie, Allergan, Amgen, Anacor, Boehringer Ingelheim, Celgene, Dermira, Eli Lilly, Galderma, Janssen, Leo, Merck & Co, Neothetics, Novartis, Pfizer, Regeneron, Symbio/Maruho, Vitae, and Xenoport. Kim A. Papp has served as a consultant; scientific officer; member of a speaker’s bureau, advisory board, or steering committee for or received research grants or honoraria from AbbVie, Akesis, Akros, Allergan, Alza, Amgen, Anacor, Artax Biopharma, Astellas, AstraZeneca, Bausch Health, Baxter, Baxalta, Boehringer Ingelheim, Bristol-Myers Squibb, Can-Fite BioPharma, Celgene, Celtic Pharma, Cipher, Dermira, Dow Pharma, Eli Lilly, Ferring, Formycon, Forward Pharma, Fujisawa, Funxional Therapeutics, Galderma, Genentech, Genexion, Genzyme, Gilead, GlaxoSmithKline, Janssen, Kyowa Hakko Kirin Co, Leo, MedImmune, Meiji Seika Pharma Co, Merck & Co (MSD), Merck Serono, Mitsubishi Tanabe Pharma, Mylan, Novartis, NovImmune, Pan-Genetics, Pfizer, Regeneron, Roche, Sanofi-Aventis, Stiefel Laboratories, Takeda, UCB, and Vertex Pharmaceuticals. Scott Guenthner serves as a speaker for Janssen, Pfizer, AbbVie, Sun Pharma, and Aclaris. Radhakrishnan Pillai is an employee of Bausch Health Americas and may hold stock and/or stock options in the company. Robert J. Israel is an employee of Bausch Health US, LLC and holds stock and/or stock options in the company. Abby Jacobson is an employee of Ortho Dermatologics and holds stocks and/or stock options in Bausch Health US, LLC.

Figures

Fig. 1

Patient disposition. Q2W every 2 weeks

Fig. 2

Percentage of patients with sPGA score of 0 (clear) or ≤ 1 (clear or almost clear) at each study visit. Observed data analysis. Error bars show the 95% confidence interval. The red arrow indicates introduction of the protocol amendment that allowed dose reductions to brodalumab 140 mg for patients weighing ≤ 100 kg. The green arrow indicates introduction of the protocol amendment that allowed dose increases to brodalumab 210 mg for patients demonstrating an insufficient response with the 140-mg dose. n number of patients who had a valid measurement value at the specified week, sPGA 0 and sPGA ≤ 1 static physician’s global assessment score of 0 and ≤ 1. aAt week 264, patients had been off treatment for ≥ 6 weeks

Fig. 3

Percentage of patients with skin clearance response measured by PASI at each study visit. Observed data analysis. Error bars show the 95% confidence interval. The red arrow indicates introduction of the protocol amendment that allowed dose reductions to brodalumab 140 mg for patients weighing ≤ 100 kg. The green arrow indicates introduction of the protocol amendment that allowed dose increases to brodalumab 210 mg for patients demonstrating an insufficient response with the 140-mg dose. n number of patients who had a valid measurement value at the specified week; PASI 75, 90, and 100 psoriasis area and severity index 75%, 90%, and 100% improvement. aAt week 264, patients had been off treatment for ≥ 6 weeks

Fig. 4

Percentage of patients with DLQI 0/1 at each study visit. Observed data analysis. Error bars show the 95% confidence interval. The red arrow indicates introduction of the protocol amendment that allowed dose reductions to brodalumab 140 mg for patients weighing ≤ 100 kg. The green arrow indicates introduction of the protocol amendment that allowed dose increases to brodalumab 210 mg for patients demonstrating an insufficient response with the 140-mg dose. DLQI 0/1 dermatology life quality index 0 or 1, n number of patients who had a valid measurement value at the specified week. aAt week 264, patients had been off treatment for ≥ 6 weeks

Fig. 5

Percentage of patients with DLQI 0/1 by skin clearance response, as measured by categories of PASI improvement from baseline (PASI 75 to DLQI 0/1 dermatology life quality index 0 or 1, n number of patients who had a valid measurement value at the specified week, PASI 75, 90, and 100 psoriasis area and severity index 75%, 90%, and 100% improvement. aAt week 264, patients had been off treatment for ≥ 6 weeks