Brentuximab Vedotin in Severe Systemic Sclerosis: Data on Long-Term Follow-Up and Retreatment

Abstract

Objectives We previously reported skin and forced vital capacity (FVC) improvements in an open-label clinical trial exploring the use of brentuximab vedotin (BV) in patients with severe diffuse cutaneous systemic sclerosis (dcSSc).[1] Long-term outcomes after therapy was discontinued, and retreatment experience remain unknown. Methods Observational study including the participants completing the original Brentuximab vedotin case series. Retreatment was authorized by Health Canada if the modified Rodnan skin score (mRSS) increased ≥6 or immunosuppression failure. Three of 10 patients received a new course of BV. The mRSS and pulmonary function tests were assessed at baseline, end of treatment (week 52), and during follow-up (as per usual clinical practice) until last visit or death. Results Ten patients were included (Table 1). Six were female (60%), with a median age at the end of the initial study of 62 (SD 14.1) years. Disease duration at the time of the first BV cycle was 4.7 years (SD 3.4). The mean change in mRSS after the original BV treatment (week 0 to 52) was −11.3 (5.8 SD). Patients were followed for up to week 192 (last follow up visit or death). At week 104, 5 patients had mRSS worsening (≥6 points) and 5 remained relatively stable. Three patients were retreated intravenous BV 0.6mg/Kg every 3 weeks: patient #5 had skin progression 3 years after finishing the original trial despite background immunosuppression, mRSS improved from 30 to 24; patient #10 had skin progression at week 108 with lack of response to initial BV treatment, her mRSS started at 29 and increased to 34; and patient #11 due to skin contracture progression while on standard immunosuppression, his mRSS progressed from 29 to 48 at week 104, dying and he died from scleroderma renal crisis (SRC) during retreatment. By week 156, 4 out of 10 patients had died due to SSc complications. One patient (who dropped out early due to PAH progression) received a lung transplant. Another one developed new onset PAH. For the remaining patients, 3 had a stable mRSS compared to week 52 over follow-up; and 3 worsened. Most received concomitant immune suppression. Table 1. Treatment and skin evolution during long-term follow-up Conclusion Half of the patients treated with BV experienced scleroderma skin progression within the first year after the last infusion, despite standard of care immunosuppression. Retreatment with BV might be beneficial but data are heterogeneous, and the timing of retreatment is unknown. References [1.] Fernández-Codina A. Rheumatology (Oxford) 2025;64:1476-81.