Burnt-Out but Still Declining: Antifibrotic Therapy in Fibrotic Sarcoidosis
Two decades into pulmonary sarcoidosis, a dedicated gardener's disease has stopped showing signs of active inflammation but keeps declining anyway — the disagreement is between two options neither of which is actually proven for her.
R.P., a 58-year-old woman, has spent the twenty-four years since her sarcoidosis diagnosis at thirty-four building a dahlia garden that now takes up most of her backyard, entering competitions most summers and staying out past dusk deadheading blooms longer than her pulmonologist would probably like. Two decades of intermittent flares and remissions have left her with what her pulmonologist now calls burnt-out disease — fibrocystic upper-lobe changes, traction bronchiectasis, and early honeycombing on her most recent CT, findings that describe scarring rather than ongoing inflammation. She has been stable for years on low-dose prednisone and methotrexate, with a normal ACE level, no new lymph node enlargement, and nothing on serial imaging to suggest active granulomatous disease is still driving anything. And yet her FVC has fallen from 61% to 52% predicted over the past eighteen months, a decline that has continued at essentially the same pace regardless of whether her immunosuppression has been held steady or briefly increased.
The INBUILD trial, which established nintedanib for progressive fibrosing interstitial lung disease broadly, is thinner ground for her than it first sounds. Wells and colleagues' diagnosis-subgroup analysis divided its 663 patients five ways, and sarcoidosis was not one of the five — twelve sarcoidosis patients in total sat inside an 81-patient “other ILDs” category alongside several unrelated diagnoses. There was never a sarcoidosis subgroup to read; twelve patients out of 663 is under two percent, not the tenth of the trial it is sometimes described as. Laboratory work has shown nintedanib can suppress the same fibrosis-promoting fibroblast behavior in cells taken from fibrotic-sarcoidosis lungs as it does in IPF, a mechanistic argument rather than a clinical one, and a dedicated randomized trial in fibrotic sarcoidosis (NCT06479603) is still recruiting, its result not yet known. Nobody in the room can fully rule out a smoldering inflammatory component her imaging and labs are simply not sensitive enough to catch. What removes the option of waiting to find out is her own arithmetic: nine points of FVC in eighteen months, holding steady, is six points a year; unchanged, that puts her near 40% predicted inside two years and into the forties within months. Whatever is chosen has to be chosen now, and on evidence that will not improve before her lungs do.
Two kinds of uncertainty
Add nintedanib. INBUILD gives us trial-level precedent for antifibrotic therapy in progressive fibrosing disease broadly — not for sarcoidosis specifically, I'll say that before you do — and separate laboratory work shows it suppresses fibroblast activity in fibrotic-sarcoidosis cells specifically. Her decline hasn't moved regardless of whether we've held or increased her immunosuppression — that pattern points past inflammation as the active driver.
You're right that her decline hasn't tracked with immunosuppression changes. But a normal ACE level and stable imaging don't rule out ongoing granulomatous disease that routine surveillance simply can't see; infliximab is the guideline-recommended step for refractory pulmonary sarcoidosis, and I'm not ready to call this fibrosis-only.
“Hasn't tracked with immunosuppression changes” assumes we've actually tested that — a brief steroid increase without infliximab's mechanism isn't the same test as a real escalation.
The dedicated randomized trial of nintedanib in fibrotic sarcoidosis is still recruiting, and INBUILD never had a sarcoidosis subgroup at all — twelve patients out of 663, folded into an “other ILDs” bin. Neither of us has a proven answer for her specifically. I'd rather pick one option, define in advance what counting as improvement would look like, and be honest that we might be wrong, than treat either choice as more settled than it is.
Agreed: start nintedanib for a defined six-month trial, with FVC checked at three months against her own established decline rate as the explicit benchmark for whether it's working.
Not agreed: what happens if it doesn't — the rheumatologist would move to infliximab next; the pulmonologist would want to reconsider the fibrotic diagnosis itself before escalating immunosuppression further.