title: Itolizumab in combination with methotrexate modulates active rheumatoid arthritis: safety and efficacy from a phase 2, randomized, open-label, parallel-group, dose-ranging study.
abstract: The objective of this study was to assess the safety and efficacy of itolizumab with methotrexate in active rheumatoid arthritis (RA) patients who had inadequate response to methotrexate. In this open-label, phase 2 study, 70 patients fulfilling American College of Rheumatology (ACR) criteria and negative for latent tuberculosis were randomized to four arms: 0.2, 0.4, or 0.8 mg/kg itolizumab weekly combined with oral methotrexate, and methotrexate alone (2:2:2:1). Patients were treated for 12 weeks, followed by 12 weeks of methotrexate alone during follow-up. Twelve weeks of itolizumab therapy was well tolerated. Forty-four patients reported adverse events (AEs); except for six severe AEs, all others were mild or moderate. Infusion-related reactions mainly occurred after the first infusion, and none were reported after the 11th infusion. No serum anti-itolizumab antibodies were detected. In the full analysis set, all itolizumab doses showed evidence of efficacy. At 12 weeks, 50 % of the patients achieved ACR20, and 58.3 % moderate or good 28-joint count Disease Activity Score (DAS-28) response; at week 24, these responses were seen in 22 and 31 patients. Significant improvements were seen in Short Form-36 Health Survey and Health Assessment Questionnaire Disability Index scores. Overall, itolizumab in combination with methotrexate was well tolerated and efficacious in RA for 12 weeks, with efficacy persisting for the entire 24-week evaluation period. (Clinical Trial Registry of India, http://ctri.nic.in/Clinicaltrials/login.php , CTRI/2008/091/000295).
authors.affiliation: Department of Rheumatology, Center for Rheumatic Disease, Pune, India.
authors.forename: Arvind
authors.initials: A
authors.lastname: Chopra
authors.affiliation: ChanRe Rheumatology and Immunology Centre and Research, Bangalore, India.
authors.forename: S
authors.initials: S
authors.lastname: Chandrashekara
authors.affiliation: Department of Orthopedics, St. John's Medical College Hospital, Bangalore, India.
authors.forename: Rajgopalan
authors.initials: R
authors.lastname: Iyer
authors.affiliation: Department of Rheumatology, Nizams institute of Medical sciences, Hyderabad, India.
authors.forename: Liza
authors.initials: L
authors.lastname: Rajasekhar
authors.affiliation: Department of Orthopedics, M.S. Ramaiah Memorial Hospital, Bangalore, India.
authors.forename: Naresh
authors.initials: N
authors.lastname: Shetty
authors.affiliation: Department of Rheumatology, Krishna Institute of Medical Sciences, Secunderabad, India.
authors.forename: Sarathchandra Mouli
authors.initials: SM
authors.lastname: Veeravalli
authors.affiliation: Department of Rheumatology, Institute of Post Graduate Medical Education and Research, Kolkata, India.
authors.forename: Alakendu
authors.initials: A
authors.lastname: Ghosh
authors.affiliation: Department of Orthopedics, Shubhechha Multispecialty Hospital, Vadodara, India.
authors.forename: Mrugank
authors.initials: M
authors.lastname: Merchant
authors.affiliation: Department of Rheumatology, LTM Medical College & LTMG Hospital, Mumbai, India.
authors.forename: Jyotsna
authors.initials: J
authors.lastname: Oak
authors.affiliation: Medicine Department and Rheumatology Clinic, TNMC & BYL Nair Charitable Hospital, Mumbai, India.
authors.forename: Vikram
authors.initials: V
authors.lastname: Londhey
authors.affiliation: Research & Development, Biocon Research Limited, Bommasandra Industrial Estate - phase IV, Bangalore, 560099, India. abhijit.barve@biocon.com.
authors.forename: Abhijit
authors.initials: A
authors.lastname: Barve
authors.affiliation: Research & Development, Biocon Research Limited, Bommasandra Industrial Estate - phase IV, Bangalore, 560099, India.
authors.forename: M S
authors.initials: MS
authors.lastname: Ramakrishnan
authors.affiliation: Research & Development, Biocon Research Limited, Bommasandra Industrial Estate - phase IV, Bangalore, 560099, India.|Center of Molecular Immunology, Havana, Cuba.
authors.forename: Enrique
authors.initials: E
authors.lastname: Montero
mesh_terms: D000284:Administration, Oral; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006801:Humans; D007194:India; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D061214:Patient Safety; D015203:Reproducibility of Results; D012219:Rheumatology / Q000379:methods; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; C000597346:itolizumab; D008727:Methotrexate
keywords: ACR; CD6; DAS-28; Itolizumab; Methotrexate; Monoclonal antibody