Nintedanib combined with dual immunosuppression for interstitial lung disease in systemic sclerosis and rheumatoid arthritis: A systematic review and pooled multicentre real-world cohort study

Interstitial lung disease (ILD) in patients with systemic sclerosis (SSc) or rheumatoid arthritis (RA) carries substantial mortality, and treatment options remain limited. We investigated the effectiveness, safety, and tolerability of triple therapy combining nintedanib with two immunomodulatory drugs in SSc- and RA-associated ILD. We carried out a systematic search of studies reporting triple combination in SSc-ILD and RA-ILD. Published and unpublished investigator-provided data were pooled into a multicentre cohort. Longitudinal variations in % predicted forced vital capacity (FVC), % predicted diffusing capacity of the lungs for carbon monoxide (DLCO), and modified Rodnan Skin Score (mRSS) in SSc-ILD were analysed at 6 and 12 months using linear mixed-effects models. The cohort comprised 64 patients (36 SSc-ILD, 28 RA-ILD). Longitudinal pulmonary function data were not available for the RA-ILD subgroup; longitudinal analyses were therefore limited to 35 SSc-ILD patients. In SSc-ILD, FVC and DLCO remained overall stable at 6 and 12 months. mRSS remained stable at 6 months, while the mixed-effects model estimated a reduction in mRSS at 12 months (−2.1 points, 95% CI -3.5 to −0.7; p = 0.002). Across the whole cohort, serious adverse events occurred in 3 patients (4.7%), including 1 death, and infections were reported in 5 patients (7.8%). Most patients (75%) continued therapy, following nintedanib dose reduction. Triple therapy was generally well tolerated in SSc- and RA-ILD. Longitudinal lung function stability and a model-based reduction in skin score were observed in the SSc-ILD subgroup. These descriptive findings support further prospective studies.