Do DMARDs affect interstitial lung disease risk in rheumatoid arthritis patients?

The choice of disease-modifying antirheumatic drug (DMARDs) used to treat rheumatoid arthritis (RA) may influence the risk of developing interstitial lung disease (ILD), a new study suggests. In a study that analyzed 16 years worth of data from a large cohort of RA patients, researchers found that treatment with tofacitinib was associated with reduced likelihood of developing ILD compared to other DMARDs. The findings may help provide a foundation for deciding how best to treat RA patients, particularly those at the highest risk for developing ILD, said rheumatologist and study co-author Dr. Matthew Baker, assistant professor of medicine at Stanford University. ILD affects at least 10% of all RA patients. And while some studies and case reports suggest certain DMARDs may impact existing ILD in RA patients, results overall have been mixed, including for specific classes of DMARDs. Indeed, there are even fewer data for more recently develop classes of DMARDs, Dr. Baker told the Medical Post in an interview. But whether any of them could potentially prevent the development of ILD has had little attention. There are three broad categories of DMARDs. The first is conventional synthetic DMARDs (csDMARDs), the older oral treatments such as methotrexate and hydroxychloroquine—generally first line ofreatment for RA. The others are biologic (bDMARDs) and targeted synthetic DMARDs (tsDMARDs). Most patients are ultimately treated with either a bDMARD or tsDMARD—making them the focus of the study, he said. “Theoretically, b/tsDMARDs could induce or worsen ILD through idiosyncratic reactions, tissue injury, or susceptibility to infection, or they may provide a therapeutic effect given the likely harmful role that inflammatory cytokines play in ILD pathogenesis,” the study said. But instead of looking at patients who already have ILD “we wanted to see if there was any signal to suggest treatment with a specific drug might potentially prevent the development of ILD,” Dr. Baker said. The nationwide, retrospective study was designed to estimate the incidence of ILD in RA patients treated with different bDMARDs or tsDMARDs, and to compare the risk of developing ILD between patients treated with those DMARDs and adalimumab. Dr. Baker noted that adalimumab was used as a standard comparator because it was the most commonly prescribed TNF-α inhibitor for RA in the population studied and the largest cohort in the study. Data from Dec. 1, 2003 to Dec. 31, 2019 were analyzed and included RA patients aged 18 years or older from the Optum Clinformatics Data Mart Database. Data for a total of 28,559 patients were included (77.6% female), were ethnically diverse and had an overall average age of 55.6 years. Patients had to have at least one year of continuous enrollment in the dataset prior to the start of their treatment and were excluded if they had a preexisting diagnosis of ILD. The drugs investigated in the study included adalimumab (the most commonly prescribed TNF-α inhibitor: 13,326 patients used this); abatacept (5,676 patients); rituximab (5,444 patients); tocilizumab (2,548 patients—the most commonly prescribed interleukin-6 inhibitor), or tofacitinib (1,565 patients—the most commonly prescribed Janus kinase inhibitor) for 180 days or more (two doses for rituximab). A total of 276 cases of ILD occurred during follow-up. Of these, 119 were in the adalimumab cohort, 60 in the abatacept cohort, 62 in the rituximab cohort, 30 in the tocilizumab cohort and five in the tofacitinib cohort. Overall, the findings showed that the incidence of ILD was lowest among patients who were treated with tofacitinib. After adjusting for key important variables, the study showed a 69% reduction in the risk of developing ILD among patients treated with tofacitinib compared with adalimumab. There was a 21% reduction in the incidence of ILD in patients treated with abatacept compared with adalimumab, but this did not reach significance. “We do not think adalimumab increases the risk. It is the comparator group, and all drugs other than tofacitinib were not statistically different than adalimumab, meaning they all have similar risks,” Dr. Baker said. Tofacitinib was the only treatment associated with a reduced risk of ILD relative to the other DMARD treatments included in the study. At this point, the data aren’t strong enough to influence practice, Dr. Baker said. It is largely a hypothesis generating study and highlights an area that is worthy of further investigation. “It is certainly interesting data,” said rheumatologist Dr. Jean-Philip Deslauriers, a clinical professor of medicine at the University of Sherbrooke, who was not involved in the study. He noted that, “for established RA-ILD we usually avoid TNF's and favor CD20 (rituximab) and CD80/86 (Abatacept). It would be interesting to see future studies look deeper into this idea of ILD prevention and the various DMARDs.”

Do DMARDs affect interstitial lung disease risk in rheumatoid arthritis patients?

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