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Hydroxychloroquine + pirfenidone is a combination therapy consisting of the immunomodulatory antimalarial agent hydroxychloroquine and the antifibrotic agent pirfenidone. This combination is being explored for the management of Rheumatoid Arthritis-associated Interstitial Lung Disease (RA-ILD), particularly in patients with a Usual Interstitial Pneumonia (UIP) pattern. Hydroxychloroquine, a 4-aminoquinoline derivative, acts by increasing lysosomal pH and inhibiting toll-like receptors (TLR7 and TLR9), which reduces the activation of the innate immune system and manages the articular manifestations of rheumatoid arthritis. Pirfenidone is an orally active small molecule that exerts antifibrotic and anti-inflammatory effects by inhibiting the production of transforming growth factor-beta (TGF-beta) and tumor necrosis factor-alpha (TNF-alpha), thereby reducing fibroblast proliferation and collagen synthesis. The combination aims to simultaneously address the systemic autoimmune inflammation and the progressive pulmonary fibrosis characteristic of RA-ILD.
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