What is your approach to treatment for a patient with progressive ILD (UIP pattern) with high titer RF but no articular symptoms?

Hello and thank you for this question. It is very important. But I need more facts to safely answer this question.

My very first thought is that assessment (i.e., a thorough history and physical exam) is highly operator-dependent. In most cases, the historical and exam findings of systemic autoimmune disease are overlooked not just by pulmonologists but also rheumatologists. Even in our JAMA report of RA ILD in 2008, there were cases where symptomatology had initially been overlooked.

If the rheumatoid factor (RF) is elevated, I am always mindful to check for HCV, which is associated with elevated RF factor alone, (i.e. could this be IPF in a person also with yet untreated HCV?). This is especially relevant in the VA patient population whereby about 20% have been HCV positive.

Additionally, what are the acute phase reactants doing (i.e., ESR, CRP, platelets, albumin (negative APR))? Be mindful that even if they are in the normal range, that alone may not rule out RA-related pulmonary disease. It is just another clue to add to the overall picture.

If after careful and detailed questioning, which seems a lost art in this day and age, there truly is no other systemic findings or report, then carefully consider whether this could be IPF and may possibly need to follow the diagnostic pathway for atypical presentation, especially if in an older white male.

If it is rapidly progressive (barring punctuated exacerbation events), it may not be IPF and in my book should be treated as a CTD ILD. This approach is to give the patient a chance at survival and decreased disability.

Another very important clarifying question that can answer this question and could also help further characterize the underlying entity is; "What is the rate of progression, i.e., FVC decline?," and "What are the characteristics of the patient?"

Progressive in the real clinical world has multiple patterns and treatment should be targeted to disease behavior.

Nintedanib might be okay for a patient with slow seepage, as I call it, of FVC (e.g., a few percentage points over a year). But it is not sufficient to save a life in the rapidly progressive phenotype which means that it is not sufficient for rescue and not sufficient for the early stages of maintenance. And, in my opinion, it is relegated at least until disease activity has quiesced to a 3rd line agent.

But if I felt confident this was RA and moderately progressive, in a person without contraindications, I would rescue with rituximab whilst initiating MMF (anti-lymphocytic, strong anti-fibrotic) for maintenance - and taper glucocorticoids as soon as able. I usually keep a close eye on these patients with close communication to inform GC taper-down while tapering up MMF.

MMF- I have very good experience with the following: start 500mg BID for 1 to 2 weeks depending on patient tolerance, and add 500mg every 5 days to a goal of 3 gram daily divided BID. If patients have GI side effects, we drop down to the previous dose and stay there for a week or two and then re-escalate and of course monitor CBC.

Before starting any immunosuppression, if at all possible, vaccinate and always check hepatitis and TB profiles. I also give Shingrix when I can and provide anticipatory guidance on shingles symptoms and a window for treatment.

I always provide anticipatory guidance regarding MMF or nintedanib and a protocol for side effects but MMF has generally worked out better than nintedanib (re: managing GI side effects).

Thanks for this question. Though, more background is needed for a safe and complete answer.

Stay safe everyone.