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Patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) had slower rates of decline in lung function over 1 year when treated with nintedanib (Ofev), an intracellular inhibitor of tyrosine kinases, according to a post-hoc analysis from a larger trial known as INBUILD.

Among patients with RA-ILD randomized to nintedanib, the rate of decline in forced vital capacity (FVC) at 52 weeks was -82.6 mL/year compared with a rate of -199.3 mL/year among those receiving placebo, which represented a difference of 116.7 mL/year (95% CI 7.4-226.1, P=0.037), reported Clive Kelly, MD, of Newcastle University in Newcastle upon Tyne in England, at the European League Against Rheumatism virtual congress.

INBUILD included 663 patients who had a chronic fibrosing ILD other than idiopathic pulmonary fibrosis. Eligible patients also had reticular abnormalities with traction bronchiectasis of at least 10% on high-resolution CT, FVC of at least 45% predicted, and diffusing capacity of the lungs for carbon monoxide of 30% to 80% predicted, and met criteria for progression of ILD within the 2 years prior to screening despite management considered appropriate.

Patients could be taking stable doses of medications for RA or connective tissue disease at baseline, except azathioprine, cyclosporine, mycophenolate mofetil (Cellcept), tacrolimus, rituximab (Rituxan), cyclophosphamide, or oral glucocorticoids in dosages above 20 mg/day. (These therapies were subsequently allowed after 6 months in patients whose lung or autoimmune disease deteriorated.)

In the primary analysis of INBUILD that included all patients, the annual rate of decline in FVC was -80.8 mL/year in the nintedanib group versus -187.8 mL/year in the placebo group, for a difference of 107 mL/year (95% CI 65.4-148.5, P<0.001). This represented a relative reduction of 57%, Kelly noted.

Of the 663 patients enrolled in the trial, 89 (13.4%) had RA-ILD. In this subgroup, the mean age was 67, 60% were men, and two-thirds were current or former smokers. The time since RA diagnosis was 10 years, and the time since ILD diagnosis was 3 years.

Of these patients, 21% were taking biologic medications, more than half were receiving disease-modifying antirheumatic drugs (DMARDs), and 73% were taking glucocorticoids in dosages below 20 mg/day. Median baseline C-reactive protein (CRP) level was 8.2 mg/L in the nintedanib group and 3.8 mg/L in the placebo group.

"The decline of 116.7 mL/year in the RA-ILD subgroup was consistent with what was seen in the overall population, and there was a clear separation between the active and placebo group at 36 weeks," Kelly said.

He and his colleagues then performed a subgroup analysis of rate of decline in FVC according to CRP level at baseline. No differences were seen in rate of decline in patients whose CRP level was above or below 1 mL or 3 mL. "This analysis was limited by small numbers, but the interaction P values of 0.73 with the 1 mL cutoff and 0.40 for the 3 mL cutoff did not indicate heterogeneity in the effect of nintedanib in these subgroups," he explained.

A similar lack of heterogeneity was observed when the rate of FVC decline was compared among patients using DMARDs and/or glucocorticoids, with a nonsignificant interaction P value of 0.76, he noted.

The adverse event profile was also similar to what was seen in the overall population, with the most common event being diarrhea, reported in 55% of the nintedanib group versus 26% of the placebo group. Other adverse events included bronchitis, nausea, and dyspnea, and treatment was discontinued in 19% of the nintedanib group and 13% of the placebo group.

"In conclusion, in INBUILD, nintedanib slowed the rate of decline in FVC in patients with progressive fibrosing ILD, with adverse events that were manageable for most patients," Kelly said. In this post-hoc analysis of the RA-ILD subgroup, "the efficacy and safety were consistent with the overall trial population," he concluded.

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