Methotrexate plus infliximab was not superior to methotrexate plus intravenous corticosteroid for inducing remission in treatment-naïve patients in the Infliximab as Induction Therapy in Early Rheumatoid Arthritis (IDEA) Trial.
Participants in the 18-month, phase IV, randomized, controlled, superiority trial were treated using a rapid remission strategy followed by a treat-to-target approach. At week 50 after the start of treatment, the mean change in modified total Sharp-van der Heijde score (mTSS) was 1.20 in 55 patients in the infliximab group, compared with 2.81 in 57 patients in the intravenous corticosteroid group, Dr. Jackie L. Nam of the University of Leeds (England) and her colleagues reported (Ann. Rheum. Dis. 2013 Aug. 2 [doi:10.1136/annrheumdis-2013-203440]).
An mTSS score of less than 2.0, indicating radiographic nonprogression, was achieved by week 78 in 80.6% of patients who received infliximab and in 71% of those who received steroid (odds ratio, 1.77), and an mTSS of less than 0.5 was achieved by week 78 in 61.9% and 46.7% of patients in the groups, respectively.
The clinical and radiographic findings of this study "support the call to treat to target. They confirm benefit of methotrexate and biologic combination therapies in early DMARD [disease-modifying antirheumatic drugs]–naive RA with the potential for drug de-escalation. Additionally, they demonstrate the benefit of combination therapy with methotrexate and steroid given here initially as a single intravenous dose," Dr. Nam and her associates wrote. However, longer-term outcomes could refine the conclusions drawn thus far from the study, and some effects of the treatments remain to be determined, particularly on bone and cardiovascular risk.
An exploratory analysis suggested that more patients in the infliximab group had early remission, which was defined as a Disease Activity Score 44 (DAS44) of less than 1.6 for 6 months. Although early remission occurred in 18.3% of infliximab-treated patients and 7.1% of steroid-treated patients (OR, 5.02), the proportion of patients achieving DAS44 remission did not differ significantly between the groups at weeks 26, 50, or 78. At week 78, for example, 47.7% and 50% in the infliximab and steroid groups, respectively, achieved DAS44 remission (OR, 1.12), the investigators said.
No substantive differences in adverse events were seen between the two groups: 98.2% of patients in the infliximab group and 94.7% in the steroid group reported adverse events. The most common were noninfectious gastrointestinal events and pulmonary/upper respiratory infections. A total of 20 serious AEs occurred in 13 patients in the infliximab group and 9 occurred in 9 patients in the steroid group, and two serious infections occurred in each group, they noted.
Patients in the multicenter trial were adults aged 18-80 years with a DAS44 of 2.4 or greater and symptom duration that ranged from 3 to 12 months. They were recruited from five sites in West Yorkshire, England, from September 2006 to July 2009, and were blinded to their treatment assignment until week 26. Patients in both groups received 10 mg methotrexate weekly, increasing to 20 mg or the maximum tolerated dose by week 6, along with 5 mg folic acid daily except on the methotrexate administration day.
Additionally, the infliximab group received infusions from 250-mL bags over a 2-hour period, receiving 3 mg/kg to a maximum dose of 1,000 mg at weeks 0, 2, 6, 14, and 22. The steroid group received 250 mg intravenous methylprednisolone at week 0, and placebo infusions at weeks 2, 6, 14, and 22.
"Disease activity was measured at weeks 0, 6, 14, 22, 26, 38, 50, 68, and 78. From week 26, during an open label observation period, patients continued therapy according to a pragmatic predetermined study escalation protocol with dose adjustment or DMARD change in the infliximab group, and DMARD escalation in the intravenous steroid group if DAS44 was greater than 2.4," the investigators wrote.
Infliximab was discontinued for sustained remission, defined as DAS44 less than 1.6 for 6 months.
This study was supported by a research grant from the Investigator-Initiated Studies Program of Merck Sharp & Dohme. Dr. Nam reported receiving speakers bureau fees from UCB. Several other study authors reported receiving grant funding, consultancy fees, and/or honoraria, and also serving on speakers bureaus or advisory boards for numerous pharmaceutical companies, including AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Centocor, Chugai, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Janssen Biologics, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Roche-Chugai, Sanofi-Aventis, Schering-Plough, UCB, and Vertex.