When you don’t use anti-fibrotics in RA-ILD Save

RA-ILD occurs in somewhere up to 10% of patients with RA. It is a serious complication with significant morbidity and mortality attached to it. 

In terms of the management of RA-ILD we are in a curious situation where we have become polarised in two different directions. There are those who look at the historically poor prognosis of RA-ILD and the irreversibility of established pulmonary fibrosis and advocate for aggressive treatment of all patients with combination therapies of biologic agents and anti-fibrotic drugs. This emerges from similar concepts in other areas of medicine with a conceptualisation of the issue as “time is lung” and “once you’ve lost your lung function there is no going back”. I myself am guilty of this at times, out of a genuine concern that if you wait to see who will get worse, it will be too late. At the other end of the spectrum there are the group of “wait and see” rheumatologists out there who can end up observing patients with slowly but steadily declining lung function tests until things have progressed past a tipping point. This approach can be engendered because symptoms are frequently a late symptom in RA-ILD, only occurring after substantial loss of pulmonary reserve, and it is ingrained in most rheumatologist’s world view that treating asymptomatic conditions is wrong. As with most things in life, the truth, and in this case the appropriate clinical approach, likely lies somewhere in between. 

It is in this setting that the results of Abstract 0448, presented in Sunday’s poster session (Rheumatoid Arthritis – Treatment Poster A) piqued my interest. This study looked at the effect of adding nintedanib to abatacept in RA-ILD. This comes from the same Spanish group who have pioneered the study of abatacept in RA-ILD. 

Now I will say at the start that there are significant limitations to this data. There are 526 RA-ILD patients treated with abatacept in this study, but only 19 of them received nintedanib, so numbers are small. There is also the shared limitation of many of the previous work here with abatacept in that this is a national multicentre observational study, it is not a randomised controlled trial.

The aim here was to compare patients treated who had nintedanib added to abatacept with those who remained on abatacept alone. There was then a stratification into those who had progressive and non-progressive pulmonary disease. Progressive ILD was defined as either 1) a >= 10% absolute decline in FVC or b) a 5-9% relative decline in FVC combined with clinical and/or radiologic progression over the 24 months after starting abatacept. 

So, what did the authors find? 

In patients who had previously progressive ILD, nintedanib+abatacept was associated with stabilisation of lung function with no relevant decline up to 48 months, whereas abatacept alone was associated with a more variable course. In patients with previously non-progressive ILD, FVC remained stable irrespective of whether nintedanib was added or not.

I guess part of the reason I like this study is that it fits with my priors. I fundamentally believe that the first action in managing RA-ILD is to manage the autoimmune RA process fully (in this case with abatacept). In my opinion the role of anti-fibrotics is secondary and they should certainly be utilised as a next step, but only in those who need them. Anti-fibrotics are associated with frequent quality of life impairing adverse events such as nausea and anorexia, and so aren’t as benign an intervention as often portrayed. The data here supports the suggestion that the role of anti-fibrotics is in those patients who have progressive pulmonary fibrosis after being established on effective immunomodulating treatment. Once that is present I fully agree that they should be instituted as quickly as possible to prevent further decline in lung function.