Immunosuppression therapy was associated with an improved trajectory in forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO) in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD), according to study findings published in Chest.
Investigators hypothesized that immunosuppression therapy would positively affect the pulmonary trajectories of patients with RA-ILD, but that the response would be impeded in patients in whom high-resolution computed tomography showed a usual interstitial pneumonia (UIP) pattern.
The investigators conducted a multi-site retrospective cohort study of 212 patients with RA-ILD from 5 US tertiary ILD centers who were being treated with azathioprine (AZA; n=92 [43.4%]), mycophenolate mofetil (MMF; n=77 [36.3%]), or rituximab (RTX; n=43 [20.3%]). All participants had at least 1 value for FVC or DLCO for both before and after treatment initiation. Participants’ mean [SD] age was 63.5 [14.6] years; 62.3% were women; and 59.7% had a history of ever smoking.
Researchers analyzed change in lung function before and after treatment using a linear spline mixed effect model with random intercept. Lung function values associated with non-use of immunosuppressives were projected based on pre-treatment values and trajectories. Participants’ predicted mean response after 12 months of immunosuppressive therapy was compared with the projected potential mean response associated with non-use of immunosuppressives at 12 months.
A total of 865 FVC measures were obtained between the 24 months before and after treatment (333 before treatment and 532 at or after treatment), and 714 DLCO measures were available (275 before treatment and 439 at or after treatment). The median follow-up was 27.5 months during the observation period of 2000 to 2021.
The collective effect of immunosuppression with AZA, MMF, or RTX on lung function trajectory after ILD treatment initiation showed that the mean FVC percent predicted after 12 months was significantly higher (3.90%; P <.001; 95% CI, 1.95-5.84) compared with the potential mean response that would have been observed if the predicted pretreatment trend of FVC percent predicted had continued.
The effect of immunosuppression on the predicted DLCO percent predicted response after 12 months of treatment was associated with a significant improvement (4.53%; P <.001; 95% CI, 2.12-6.94) vs the potential mean response that would have been observed if the pretreatment trend had continued.
The non-UIP and UIP groups both had significantly improved FVC percent predicted compared with pretreatment trends (3.36%; P =.012; 95% CI, 0.74-5.98; and 4.74%; P =.003; 95% CI, 1.64-7.83, respectively), based on the interaction model. Presence of UIP did not significantly affect the response trajectory over time (interaction between UIP and spline variable, P =.5), with a comparable result observed for DLCO percent predicted (interaction P =.9).
No significant differences were observed in FVC percent predicted response between immunosuppressive therapy agents (AZA vs MMF, P =.8; AZA vs RTX, P =.8). In addition, no significant differences were found in DLCO percent predicted response among the therapies (AZA vs MMF, P =.595; AZA vs RTX, P =.1).
The researchers noted that their study design limited their ability to comment on the impact of immunosuppressive treatment on other outcomes such as RA disease control, quality of life, hospitalizations, and mortality. Also, referral bias was possible, they noted, as the 5 sites were tertiary ILD referral centers and likely included patients with RA-ILD who had more severe disease and were potentially more likely to have progression.
“Our data supports the current paradigm of primary, initial immunosuppression for treatment of rheumatoid arthritis interstitial lung disease regardless of underlying interstitial lung disease pattern,” concluded the study authors. “However, the limitations of observational and retrospective study design highlight the urgency for randomized, placebo-controlled trials in RA-ILD.”
Matson SM, Baqir M, Moua T, et al. Treatment outcomes for rheumatoid arthritis associated interstitial lung disease; a real-world, multisite study of the impact of immunosuppression on pulmonary function trajectory. Chest. Published online December 2, 2022. doi:10.1016/j.chest.2022.11.035