Efficacy and safety of itolizumab, a novel anti-CD6 monoclonal antibody, in patients with moderate to severe chronic plaque psoriasis: Results of a double-blind, randomized, placebo-controlled, phase-III study
Authors: Sandesh Gupta
Kotla Sai Krishna
Prasanna C Ganapathi
Dasiga Venkata Subrahmanya Pratap
T Narayana Rao
T K Sumathy
Radha Shah
Neeraj Pandey
D S Krupashankar
Pradip Nair
Uday Khopkar
Leelavathy Budamakuntla
M S Ramakrishnan
Vijay Garg
Dalavoi Padmaja
M G Gopal
Narendra Shetty
Mahendra Kura
Sunil Dogra
Abir Saraswat
G Manmohan
Enrique Montero
Ramesh Bhat
C R Srinivas
Journal: Journal of the American Academy of Dermatology (2014)
Discipline: CLINICAL MEDICINE
Keywords: Psoriasis Area and Severity Index; anti-CD6; autoimmune disease; itolizumab; monoclonal antibody
Affiliations: Manipal Hospital, Bangalore, India., Postgraduate Institute of Medical Education and Research, Chandigarh, India., Grant Medical College and JJ Group of Hospitals, Mumbai, India., Indushree Skin Clinic, Lucknow, India., Bowring and Lady Curzon Hospitals, Bangalore, India., M S Ramaiah Memorial Hospital, Bangalore, India., Apollo Hospital, Hyderabad, India., Kempegowda Institute of Medical Sciences, Bangalore, India., King George Hospital, Visakhapatnam, India., PSG Hospitals, Coimbatore, India., Father Muller Medical College and Hospital, Mangalore, India., AJ Institute of Medical Sciences, Mangalore, India., Derma Skin Clinic, Hyderabad, India., Sri Sai Skin Clinic, Hyderabad, India., Sumana Hospital, Hyderabad, India., Durgabhai Deshmukh Hospital, Hyderabad, India., Maulana Azad College and Lok Nayak Hospital, New Delhi, India., Skin and Laser Center, Delhi, India., DermaKlinic Skin, Laser and Cosmetic Clinic, Lucknow, India., Seth G.S. Medical College and KEM Hospital, Mumbai, India., Center of Molecular Immunology, Havana, Cuba; Biocon Research Limited, Bangalore, India., Biocon Research Limited, Bangalore, India., Biocon Research Limited, Bangalore, India. Electronic address: .

Abstract:  Background: Itolizumab, a humanized monoclonal antibody to CD6, is a novel therapeutic agent evaluated in chronic plaque psoriasis. Objective: We sought to assess the safety and efficacy of itolizumab in moderate to severe chronic plaque psoriasis. Methods: A total of 225 patients were randomized (2:2:1) to 2 different itolizumab arms (A or B; A = 4-week loading dose of 0.4 mg/kg/wk followed by 1.6 mg/kg every 2 weeks; B = 1.6/mg every 2 weeks) or placebo. At week 12, the placebo arm was switched to 1.6 mg/kg itolizumab every 2 weeks. The primary end point was the proportion of patients with at least 75% improvement in Psoriasis Area and Severity Index score at week 12. Results: At week 12, 27.0% in arm A (P = .0172 vs placebo), 36.4% in B (P = .0043 vs placebo), and 2.3% in the placebo arm had at least 75% improvement in Psoriasis Area and Severity Index score. At week 28, the proportion with at least 75% improvement in Psoriasis Area and Severity Index score was comparable: 46.1%, 45.5%, and 41.9% for A, B, and placebo, respectively. In weeks 1 to 12, the incidence of all adverse events was comparable across arms (A, 43%; B, 38%; placebo, 47%) and the incidence of infections was not greater than placebo (11.1%, 8.9%, and 18.6% for A, B, and placebo). Limitations: No active comparator is a limitation. Conclusions: Itolizumab is an effective and well-tolerated novel biological therapy in moderate to severe psoriasis. 

Retracted: No

PubPeer comments:
 Article [1] claims to perform intent-to-treat (ITT) analysis determine efficacy and safety of itolizumab in patients with moderate to severe chronic plaque psoriasis. However, they exclude five patients who were randomized and sent to treatment arms A and B. A total of 225 patients were randomized to arms A (n=91), B (n=91), C (n=43), where arms A and B were treatment arms and arm C was placebo initially. Full analysis set for ITT contained 220 patients: 89 in arm A, 88 in B, and 43 in C. 5 patients were excluded (not dosed: 1 each in A and B; withdrawn the day after the first infusion: 1 each in A and B; lost to follow-up: 1 in B). As stated in [2],  Intention-to-treat analysis is a method for analyzing results in a prospective randomized study where all participants who are randomized are included in the statistical analysis and analyzed according to the group they were originally assigned, regardless of what treatment (if any) they received. We can conclude that analysis presented in original article [1] is not proper and authors ended up doing per-protocol analysis, which is not reliable to make desired conclusion in [1]. Bibliography: [1] Efficacy and safety of itolizumab, a novel anti-CD6 monoclonal antibody, in patients with moderate to severe chronic plaque psoriasis: Results of a double-blind, randomized, placebo-controlled, phase-III study, http: dx.doi.org 10.1016 j.jaad.2014.01.897 [2] Understanding the Intention-to-treat Principle in Randomized Controlled Trials, doi: 10.5811 westjem.2017.8.35985. ,