A Phase Ib Investigator-Initiated Trial of Filgotinib in Patients With Idiopathic Multicentric Castleman Disease.

Background Idiopathic multicentric Castleman disease (iMCD) is a chronic systemic inflammatory disease characterized by the production of interleukin (IL)-6. The contribution of Janus kinase, downstream of IL-6 signaling, to the pathophysiology of iMCD has been suggested by several studies. Patients and methods This phase Ib single-arm trial evaluated the safety profile and efficacy of filgotinib, a JAK1 preferential inhibitor, in patients with iMCD. We recruited patients with disease activity evaluated based on their values of C-reactive protein (CRP), hemoglobin, albumin, and Eastern Cooperative Oncology Group performance status (ECOG-PS). Filgotinib (200 mg daily) was administered for eight weeks. Results Five patients who were newly diagnosed with or under treatment for iMCD were recruited. The lymph node histology of all five patients was the plasma-cell type. Filgotinib demonstrated a favorable safety profile with manageable adverse events. At eight weeks, improvements in the ECOG-PS were observed in two patients, but no improvements in CRP, hemoglobin, or albumin levels were observed. Conclusion The safety profile of filgotinib against iMCD was comparable to those against rheumatoid arthritis and ulcerative colitis over a short duration, but the efficacy of filgotinib against iMCD was not evident after eight weeks. Long-term evaluations of the safety profile and efficacy of filgotinib in the treatment of iMCD are necessary.