Background Systemic sclerosis (SSc) is a connective tissue disease associated with chronic polyclonal B-lymphocytic activation and immunological tolerance disturbance. Rituximab (RTX) is a recombinant monoclonal chimeric antibody to C20 superficial B-cell receptors. Several research and clinical studies showed that B-cell depletion is potentially efficacious in SSc treatment. However, neither strong evidence of RTX efficacy for treatment of interstitial lung disease (ILD) associated with SSc, no clear recommendations on selection of optimal dose and treatment duration have been available.
Objectives To evaluate the impact of a-B-cell therapy with RTX on pulmonary function of the patients with ILD-SSc.
Methods A total of 54 patients with definite diagnosis ILD-SSc treated with RTX were enrolled into the study. At the time of enrollment to the study SSc duration since the first non-Raynaud syndrome was 6.5±5.7 years; male/female ratio 1:4.4; diffused/limited disease ratio 1.3:1, average age 48.5±12.9 years. Follow-up duration since the first RTX administration was 25.7±16.7 months (ranging from 6 to 72 months), average RTX dose at the time of the last examination was 2.1±1.2 g (ranging from 1100 mg to 5 g). The dynamics of FVC, DLCO and SSc activity index were evaluated in general group and in patient subgroups with the study duration ≤5 years (A, n=29) and>5 years (B, n=25). 10% and more change in FVC and DLCO were considered clinically significant.
Results In general group RTX therapy was associated with significant FVC increase from 74.5±19.6% to 82.5±22% (p=0.000006). FVC increment median was 7.5%. Clinically significant FVC increase and decrease were observed in 20 (37%) and 2 (4%) patients, respectively. FVC delta directly correlated with RTX cumulative dose (R=0.28, p<0.05) and inversely correlated with SSc activity index at the time of the last examination (R=0.3, p<0,05). In subgroup A greater FVC increase was observed compared with subgroup B (80.4±8.9% to 90.2±21.5%, p=0.017 vs 67.7±19.1% to 73.9±19.7,% p=0,06).
In general group RTX treatment did not result in significant change of DLCO level (47.4±22.1% vs 49.4±20.9%, p=0.4). DLCO increment median was 0.97%. Clinically significant DLCO increase and decrease were observed in 7 (13%) and 4 (7%) patients, respectively. DLCO delta directly correlated with RTX cumulative dose (R=0.29, p<0.05) and inversely correlated with SSc activity index at the time of the last examination (R=0.3, p<0.05). Similarly, no significant change of DLCO values was observed in subgroup A and subgroup B (51.7±19.3% - 52.8±18.5% and 35.3±12.5% - 39.2±12.4%, respectively).
Conclusions RTX therapy was associated with significant increase in FVC and DLCO stabilization. Greater FVC increase was observed in the patients with SSc duration up to 5 years. FVC and DLCO increase directly correlated with RTX cumulative dose and inversely correlated with SSc activity index at the time of last examination.
Disclosure of Interest None declared