FRI0264 EFFECTIVENESS, SAFETY AND PATTERNS OF USE OF RITUXIMAB IN SCLERODERMA, IN CLINICAL PRACTICE: 9 YEARS’ EXPERIENCE IN A TERTIARY HOSPITAL
Authors: E. Vicente, J. Fernández, I. Llorente, L. Vega, S. Castañeda, A. García-Vadillo, I. González-Álvaro, A. Humbría, A. Ortiz, E. Patiño, E. Tomero Muriel, R. Garcia de Vicuna
Journal: Annals of the Rheumatic Diseases (2020)

Background: Systemic sclerosis (SSc) is a clinically complex and heterogeneous disease. Interstitial lung involvement (ILD) is the main cause of mortality, but progression of skin fibrosis has also been associated with pulmonary dysfunction and mortality. Recently, Rituximab (RTX) has been postulated as a promising therapeutic alternative to cyclophosphamide (CF) or mycophenolate (MFM), but long-term experience is scarce. Objectives: Describe the effectiveness, safety and long-term use of RTX, in a series of cases with SSc. Methods: Retrospective observational study of patients with SSc (EULAR/ACR 2013 criteria) treated with RTX in a university hospital from 2010 to 2019. Sociodemographic data related to SSc and treatments were collected. The effectiveness of RTX was evaluated at 6-12 months and at the end of follow-up, by means of these main outcomes: Rodnan’s modified cutaneous index (mRSS) for skin fibrosis; CK leves for myopathy, variation &gt;10% in forced vital capacity (FVC) and &gt;15% in lung diffusion capacity of carbon monoxide (DLCO) for ILD. Adverse events (AE) were recorded. Statistical analysis performed with Stata v.14 and statistical significance set for p≤0.05. Results: 14 women with SSc (mean age 47±13 years, mean evolution 6.2±4.5 years) were treated with RTX for ILD (n=9), skin involvement (n=11) and/or inflammatory myopathy (n=3). The mean±SD of follow-up was 3.36±2.17 years. SSc type: diffuse cutaneous 35.71%, limited cutaneous 21.44%, overlap 35.71% and sine scleroderma 7.14%. Type of antibodies: 50% anti-Scl-70, 14.3% anti-centromere, 21.4% anti-RNA polymerase III and 7.14% anti-Ku. ILD was classified as NINE in 8 patients and NIU in 1. The first cycle of RTX included 2 infusions of 1g and was initiated a mean of 3.36±2.17 years after diagnosis. The retreatments were initially fixed every 6 months and later on demand in 4 patients, and in the rest on demand from the beginning, according to duration of clinical response. A mean of 3.9±2.5 cycles/patient (range: 1-11) were administered. 30% of patients had previously received CF and 21.5% MFM. RTX was administered in association with other DMARDs (MTX 64.29%, hydroxychloroquine [HCQ] 35.71%, MFM 57.14%, others 14.28%), CF (14.29%), intravenous immunoglobulins (7,14%) and prednisone (78.57%). In the final visit, the percentage use of DMARDs (50% MTX, 50% MFM and 28.57% HCQ) and prednisone (62.5% patients, 30% doses) was reduced. mRSS improved significantly. Muscle weakness disappeared in 3/3 with normal CK levels in 2/3 patients with myopathy. The FVC improved or stabilized in 22% and 56% of ILD, respectively, and the DLCO stabilized in 66.70% (not significant). TACAR stabilized in 55.56% of ILD, with some degree of worsening in the rest. Outcomes evolution in the Table: Functional Parameters Basal (mean±SD) 6-12 m (mean±SD) CI 95% P Final (mean±SD) CI 95% P FVC (n=9) 63.2±16.8 70.3±18.6 [-13.3–6.1] 0,40 71.9±21.1 [-14.4–5.9] 0.36 DLCO (n=9) 46.3±18.5 46.1±20.3 0,34 45.2±22.03 [-3.9–12.8] 0.24 Clinical Parameters Basal (mean ± SD ) Final (mean ± SD ) CI 95% P mRSS (n=11) 13.1±7.2 8.8±7.1 [0.9–9.4] 0.02 CK (n=3) 1786.7 ±1483.8 134.7±119 [-2181.9 –5485.9] 0.2 CK: Creatine kinase; SD: Standard deviation; CI: Confidence interval; m: months. The AE were mostly mild: 13 infusional reactions (6 patients), 1 uncomplicated herpes zoster and 2 serious infections that required admission. There were no exitus. Conclusion: Our results, with a limited sample, suggest that the long-term use of RTX in real world clinical practice may be beneficial for the cutaneous, pulmonary and myopathic manifestations of SSc, with an acceptable security profile. Disclosure of Interests: Esther Vicente Speakers bureau: BMS, Roche., Javier Fernández: None declared, Irene Llorente Speakers bureau: Gebro, Janssen, Sanofi, Lilly., Lorena Vega: None declared, Santos Castañeda: None declared, Alberto García-Vadillo: None declared, Isidoro González-Álvaro Grant/research support from: Roche Laboratories, Consultant of: Lilly, Sanofi, Paid instructor for: Lilly, Speakers bureau: Abbvie, MSD, Roche, Lilly, Alicia Humbría: None declared, Ana Ortiz: None declared, Esther Patiño: None declared, Eva Tomero Muriel: None declared, Rosario Garcia de Vicuna Grant/research support from: BMS, Lilly, MSD, Novartis, Roche, Consultant of: Abbvie, Biogen, BMS, Celltrion, Gebro, Lilly, Mylan, Pfizer, Sandoz, Sanofi, Paid instructor for: Lilly, Speakers bureau: BMS, Lilly, Pfizer, Sandoz, Sanofi