Background/Purpose: To investigate the efficacy and safety of rituximab (RTX) in the the management of progressive rheumatoid arthritis related interstitial lung disease (RA-ILD).

Methods: An open observational study was performed in patients with progressive RA-ILD (evidence of clinical and functional decline) and inadequate articular response (DAS28 > 3.2) despite treatment with glucocorticoids and synthetic DMARDs.

The following main efficacy variables were evaluated at the end of follow-up: 1) the improvement of joint counts measured by DAS28-ESR and 2) the evolution of pulmonary function tests (PFT) according to definitions from the American Thoracic Society, including a) improvement: if an increase in FVC ≥ 10% or DLCO ≥ 15% is observed; b) stabilization:  if changes in FVC are less than 10% or 15% in DLCO; and c) worsening:if FVC decreases ≥ 10% or DLCO ≥ 15%.   

Results: Thus far, 13 patients have been included (seven women) with a mean age (± SD) of 53 ± 13 years (range, 35-74). All patients were ACPA positive. 

The time of evolution (median) was 24 months (range, 8-168) for RA and seven months (range 1-16) for RA-ILD. Regarding tissue specificity, 10 (77%) cases corresponded to NSIP and three to UIP.

Once RA-ILD was diagnosed, patients with NSIP received prednisone treatment at a dose of 0.75-1 mg/kg, whereas patients with UIP were treated with prednisone at a dose of 10-15 mg/day and N-acetylcysteine at a dose of 1800 mg/day. In addition, methotrexate was substituted for leflunomide in eight patients, azathioprine in three, and salazopyrin in two.

At the start of RTX treatment (dose: 1 g on days 1 and 15, repeating the cycle after six months depending on the response), the mean DAS28 value was 5.5 ± 1.1, baseline FCV (%) was 75 ± 15, and baseline DLCO (%) was 55.5 ± 21.

At the end of an 11-month (median, range 6-111) follow-up period, the mean DAS28-ESR score decreased to 3 ± 1.3 (% improvement: -45.45%; range, -62 to -24%). In seven patients (54%), remission of the joint disease (DAS28 < 2.6) was achieved, and in six patients, there was low activity (DAS28 ≤ 3.2). The evolution of PFT values is shown in the following table:   

Considering the total sample, FCV improvement (FCV after treatment: 87 ± 18; 16% improvement) and DLCO stabilization (DLCO after treatment: 59.3 ± 22; 6.8% improvement) were achieved. The number of RTX cycles administered (mean ± SD) was 3.25 ±1.5 (range, 1-6). 

The frequency of adverse effects was low, occurring in only one patient (8%) who developed pulmonary aspergillosis at five months of treatment, forcing a temporary suspension of treatment. 

Conclusion: In our experience, RTX is a relatively safe and effective drug for the treatment of patients with active symptomatic RA-ILD and an insufficient articular response despite treatment with glucocorticoids and synthetic DMARDs. In this subgroup of patients RTX administration achieved remission/low activity of clinical joints and, at a minimum, PFT were stabilized.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/rituximab-efficacy-in-the-treatment-of-diffuse-interstitial-lung-disease-associated-with-rheumatoid-arthritis/