THU0245 Rituximab has a beneficial effect on lung function and skin fibrosis in patients with systemic sclerosis. An open label study

Abstract

Background Evidence suggests that B cells may play a role in fibrosis. We have previously shown that rituximab (RTX) may favorably affect lung function and skin fibrosis in patients with systemic sclerosis (SSc). Objectives To further assess efficacy and safety of RTX in SSc Methods Twenty five patients with diffuse SSc from two University Hospitals were recruited. All patients had evidence of lung involvement as indicated by findings in chest HRCT and pulmonary function tests (PFT). Patients received 4 weekly pulses of rituximab (375 mg/m2) at baseline and were retreated with the same scheme at 6 months. Lung function and skin thickening was assessed by PFTs and MRSS respectively, at baseline, 6 and 12 months. Data are presented as mean ± SEM, median (range) or percentages, as appropriate. Results Patients were predominately female (n=19) with a median age of 54.5 (32-77) and disease duration of 6 (1-28) years. All patients had diffuse SSc apart from 2 patients with CREST. Nine patients received concurrent immune based therapies (7 MMF, 1 MTX and 1 HCQ, all initiated at least 3 years prior to enrollment). At the 12 month evaluation time point (data available from 12 patients) a significant improvement of FVC and DLco was found (FVC: 69.1±5.6 vs 75.7±5.4 at baseline vs 12 months, respectively, p=0.001 and DLco: 54.8±5.6 vs 60.4±6 at baseline vs 12 months, respectively, p=0.008, n=12). Skin thickening improved significantly as well (mean MRSS ± SEMat 12 months: 8.75±1.6vs. 15.1±2.2at baseline, p=0.0001) an effect that was evident already at 6 months following RTX treatment (11.2±1.7, p=0.0001 vs. baseline). At the 6 month evaluation time point lung function parameters recorded a statistically significant yet perhaps a clinically questionable increase (mean FVC ± SEM: 78.6±4.4 vs 80.1±4.3 at baseline vs 6 months, respectively, p=0.047, n=25) while the improvement seen in DLco did not reach statistical significance (mean ± SEM, 60.9±3.4 vs 64±3.5 at baseline vs 6 months, respectively, p=0.13). Functional status improved as indicated by a decline in HAQ-DI (p<0.001, at 6 months compared to baseline). A beneficial effect on skin calcinosis in a patient with CREST was noted. RTX treatment was generally well tolerated. One case of respiratory tract infection requiring short term hospitalization, one case of Hepatitis B reactivation, one case of herpes zoster and two cases of mild infusion reactions were recorded. Conclusions Our data indicate that RTX can have a beneficial effect on skin fibrosis as well as lung function in patients with SSc. Skin involvement responds earlier than pulmonary function parameters; our preliminary data suggest that long-term treatment may be needed in order to enhance and sustain this effect. Treatment with RTX was well-tolerated and safe. A large-scale, randomized, controlled study is clearly needed. Disclosure of Interest None Declared

Two-year Results of an Open Pilot Study of a 2-treatment Course with Rituximab in Patients with Early Systemic Sclerosis with Diffuse Skin Involvement

“…The previously reported 6-month followup data of our study suggested that RTX was well tolerated and could safely be administered in patients with early dcSSc 16 . The 2-year followup data confirm this finding, as does work from other groups 13,14,15,17 .…”

“…The safety and potential benefits of RTX in SSc have been evaluated 13,14,15,16,17 . But to date a 2-treatment course (months 0/6) of RTX in early diffuse SSc has not been investigated.…”

Targeting B cells for treatment of systemic sclerosis

“…The same study group conducted a posthoc analysis of this study, revealing that CD19-positive cell count and high mRSS predict favourable response to rituximab [15]. The use of rituximab for SSc with interstitial lung disease (SSc-ILD) seems effective based on previous reports [20–25]. Still the efficacy should be confirmed through randomized controlled clinical trials with a larger sample size.…”

Interstitial Lung Disease Associated with Systemic Sclerosis

“…Supportive evidence of the efficacy of rituximab in SSc-ILD also came from a small sample size trial 141 and observational studies. [142][143][144] Collectively, these results indicate that patients with SSc-ILD benefit from rituximab treatment in terms of FVC, quality of life, and skin fibrosis, offering an effective treatment option for this group of patients at the expense of a manageable risk of infection. 138,140…”