Rheumatoid arthritis and interstitial lung disease: a deadly combination

Rheumatoid arthritis-associated interstitial lung disease is difficult to control. The combination of DMARDs with antifibrotics might improve the prognosis for this difficult-to-treat patient population.

“Approximately 25% of patients with rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) die in the first year after diagnosis, and only around 20% are alive 8 years after the initial diagnosis,” Prof. Joan Bathon (Columbia University, USA) said [1]. Thus, mortality is considerably higher compared with RA patients without ILD. In total, the prevalence of RA-associated ILD is estimated between 8% and 15%, a 9-fold risk elevation compared to the general population.

How RA medications influence the risk of developing ILD is a matter of debate. ”It seems unlikely that methotrexate is worsening ILD, but I don´t know whether we will ever get to the root of this problem because RA itself is causing ILD and sorting this out from the treatment is always difficult,” Prof. Bathon said.

Concerning a DMARD that may treat both ILD and arthritis, there is only scarce data for targeted DMARDs. There are open-label studies regarding B-cell depletion therapy with rituximab and T-cell co-stimulatory inhibitor therapy with abatacept that suggested disease stabilisation, for example. There is data on the IL-6 receptor blocker tocilizumab only in systemic sclerosis, not in RA-ILD. In systemic sclerosis, a slower decline in pulmonary function tests was observed in the tocilizumab group versus placebo, “so there might be some hope that an improvement might also be the case in RA,” Prof. Bathon said.

The antifibrotics nintedanib and pirfenidone are approved for idiopathic pulmonary fibrosis (IPF). The tyrosine kinase inhibitor nintedanib was also tested in patients with autoimmune disease, namely in patients with systemic sclerosis-associated ILD in the SENSCIS trial. In this study, lung function decline was reduced by about 50% in the nintedanib arm compared with the placebo group. In the INBUILD trial, nintedanib was assessed in fibrosing ILDs other than IPF: 25% of patients suffered from autoimmune ILDs, including RA. The agent slowed down lung function deterioration by 57%. “The efficacy was similar among all autoimmune ILDs. This is very encouraging because some of these patients had RA,” Prof. Bathon concluded. At present, there is no data on pirfenidone on RA-ILD, but there is a trial in progress now.

Furthermore, another question is whether it is safe to combine nintedanib or pirfenidone with a conventional DMARD and/or a targeted DMARD. “Probably. We need more data for this answer, but at least for nintedanib, we have some data from the INBUILD trial, where patients with RA were allowed to remain on DMARDs. There was no report on synergistic or added toxicity,” concluded Prof. Bathon.

1. Bathon J. RA & Interstitial Lung Disease. 3S010, ACR Convergence 2020, 5-9 Nov.

Posted on 18 January 202117 May 2024