To evaluate the safety and efficacy of infliximab, a TNFα inhibitor, in improving lung function, symptoms, and functional capacity in patients with chronic sarcoidosis with pulmonary involvement who are symptomatic despite treatment.
Patients (n=138) were randomized (1:1:1) to infliximab [3 or 5mg/kg] or placebo at 34 centers in US and EU. Patients were infused at week 0, 2, 6, 12, 18, 24 and followed through week 52. Eligibility criteria included a diagnosis of sarcoidosis for ≥1 year, an American Thoracic Society dyspnea score of ≥1 despite treatment with ≥3 months of prednisone (≥10mg) or immunomodulator therapy or both, evidence of parenchymal disease (Stage II or III) on chest radiograph and a forced vital capacity (FVC) of ≥50-≤85% predicted. The 1° endpoint was defined as the change from baseline in the % of predicted FVC at week 24. Major secondary endpoints included the St. George’s Respiratory Questionnaire, 6-minute walk distance, and Borg’s CR10 dyspnea score.
Baseline characteristics were well balanced, with 42% of patients receiving immunomodulators and corticosteroids. There was a significant improvement in the 1° endpoint in the combined infliximab group (delta 2.5%, p = 0.038). Results did not differ substantially between the infliximab doses. Subgroup analysis demonstrated greater benefit in patients with more extensive sarcoidosis disease burden, duration, activity or severity. There were no significant differences in major secondary endpoints. Ten percent of patients had infusion reactions and ∼5% discontinued treatment due to adverse events (no difference between placebo and infliximab). There were no instances of delayed hypersensitivity reactions or anaphylaxis. One patient (receiving placebo) died of respiratory failure due to pulmonary hypertension secondary to sarcoidosis.
Infliximab appears to be effective in improving pulmonary function in symptomatic patients with chronic pulmonary sarcoidosis with a reasonable safety profile.
Addition of infliximab to corticosteroid therapy with or without immunomodulators is a promising new treatment strategy. These results should be confirmed in a larger, more severely affected chronic pulmonary sarcoidosis population.
R Baughman, Grant monies (from industry related sources) Research grants; Consultant fee, speaker bureau, advisory committee, etc.; Employee.