A randomized, double-blind, placebo-controlled trial of infliximab in refractory polymyositis and dermatomyositis

Abstract

Objective: To investigate in a pilot study the safety and efficacy of infliximab in patients with refractory dermatomyositis (DM) and polymyositis (PM).

Methods: A randomized, double-blind, placebo-controlled trial including subjects with active DM or PM. Participants had stable doses of immunosuppressive medication and prednisone (≤0.5mg/kg/day), and exhibited clinical signs of muscle weakness for at least 4 weeks prior to study entry. Participants received infusions of either placebo or infliximab 5mg/kg at 0, 2, 6, and 14 weeks in blinded manner. The primary outcome was a ≥15% manual muscle strength (MMT) improvement at week 16 compared to week 0. The secondary outcome measures were improvement defined by the International Myositis Assessment and Clinical Studies Group (IMACS) criteria. At week 16, responders in each arm had the option of either continuing the same treatment or changing to the non-responder treatment for that study arm. Non-responders in the 5mg/kg infliximab arm were increased to infliximab 7.5mg/kg for weeks 22, 30, and 38. Non-responders in the placebo arm at week 16 received infliximab 5mg/kg at weeks 16, 18, 22, 30, and 38. Outcomes were reassessed at week 40.

Results: Twelve subjects completed the study to week 16. Six of the 12 subjects received infliximab treatment at the dose of 5mg/kg with only one subject meeting the responder criteria at that dose. Of the remaining five subjects on infliximab, three crossed over to the infliximab 7.5mg/kg dose. One of those three subjects responded. All six patients in the placebo arm crossed over to the 5mg/kg dosing regimen after week 16, and two of those responded to infliximab.

Conclusions: Infliximab therapy for patients with refractory PM and DM was well tolerated and may benefit a subset of patients.

Trial registration: ClinicalTrials.gov NCT00033891.

Keywords: Dermatomyositis; Infliximab; Polymyositis; TNF inhibitor.

Figure 1:

Patients were randomized to receive 4 infusions of placebo vs treatment (infliximab). Response was defined as ≥ 15% improvement in strength based on the Manual Muscle Test (MMT*). Outcomes were assessed at 16 and 40 weeks. Responders were continued on 5mg/kg of infliximab. Non- responders were started on infliximab (5 mg/kg) in the placebo arm and increased to 7.5 mg/kg of infliximab in the treatment arm. *The MMT-8 score is a summative value with a scoring range of 0 to 150. The 8 muscle groups included in the MMT-8 were tested using a 10-point scale. Muscle groups tested bilaterally were the shoulder abductors, elbow flexors, wrist extensors, knee extensors, ankle dorsiflexors, hip abductors, and hip extensors. Muscle groups tested unilaterally were the neck flexors.