Background Treatment of Systemic Sclerosis (SSc) remains challenging and some clinical studies reported the efficacy of Rituximab (RTX) in skin disease and in stabilizing lung involvement. Recently 2 randomized clinical trial demonstrated the efficacy of RTX in SSc and in lung involvement in connective tissue diseases (1,2), however current data are limited by the small number of samples examined and the short duration of follow-up.

Objectives We aimed at retrospectively evaluate the efficacy, safety, and long-term persistence of RTX therapy in a monocentric SSc cohort.

Methods All clinical records of SSc patients (pts) treated with RTX in our center were retrospectively analyzed. Demographic, clinical and disease characteristics, treatment approach, combination therapies, and adverse events during RTX were considered. Every 6 months, skin score, pulmonary function test and swollen joint count (SJC) modifications as well as digital ulcer occurrence were recorded.

Results Fifty-two SSc pts (pts) have been treated with RTX in our center since 2005. The mean age of the pts was 55.3±24.3 years and 21.5% were male. The disease duration at the time of the first treatment with RTX was 4.4±2.8 years and the mean reached follow-up was 6.6±2.2 years (range 2-17 years). Forty pts (77.0%) had a diffuse cutaneous involvement, 33 pts (63.6%) had anti-topoisomerase positivity, 45 (88.2%) an interstitial lung disease on high resolution chest CT, 30 pts (59.2%) arthritis or tenosynovitis, and finally 38 pts (73.1%) presented any history of digital ulcers. Twenty-three (44.2%) pts had been previously treated with cyclophosphamide.

During RTX treatment, 39 pts (75.0%) received an immunosuppressive combination therapy, most with mycophenolate mofetil (53.8%). Concomitant glucocorticoids treatment was assumed by the 53.8% of pts. Twenty-five pts (48.1%) were treated with Rituximab for only one clinical involvement, 27 pts (51.9%) received treatment for more than one organ involvement including skin, lung or joint. Overall, 82.7% were treated for progression of skin disease, 50.0% for lung involvement deterioration and 23.1% for active arthritis.

Treatment showed improvement in the skin score, arthritis, and/or stabilization of the pulmonary functional status in 44 pts (84.6%), while in the remaining 8 pts, therapy was stopped because of worsening of the disease over the 6 months of follow-up.

Among responders, skin score improved from 17.3±8.9 to 10.3±8.6 (p=0.04), while FVC and DLco remained stable (87.4±3.5% to 86.2±20.5% and 66.3±23.9% to 64.3±22.1%, respectively). As expected, there was an improvement in DAS28 (4.9±0.8 to 1.9±0.5, p<0.01). Finally, there was a reduction in the rate of ulcer occurrence (46.15% to 21.70%, p=0.04). Twenty-two pts (42.3%) were treated with one single cycle of therapy (1 gr two weeks apart), while the remaining 30 pts were treated with repeated cycles of RTX, with a mean number of cycles of 4.3±2.0. Among the re-treated pts, 50% were treated every year and 50.0% at the time of new clinical worsening, and retreatment was done every 60.5±31.4 months. All pts re-treated with RTX on demand responded to the therapy.

Nineteen percent of pts developed adverse events (5.7% leukopenia, 7.7% infusion reactions, 1.9% sepsis, 3.8% pneumonia). Ten pts (19.2%) died during follow-up: 8 deaths were related to organ complication of SSc and 2 to cancer.

Conclusion Our data suggest long-term efficacy and safety of RTX in pts SSc. Further real world studies will be necessary to evaluate the best therapeutic approach with RTX (regular cycles or retreatment when clinical worsening occurs) and/or the combination with other immunosuppressant drugs.

References [1]Ebata S, Lancet Rheumatol 2021;3:e489–97.

[2]Maher TM, Lancet Respir Med. 2023 Jan;11(1):45-54.

Acknowledgements: NIL.

Disclosure of Interests None Declared.