Background Current pharmacological treatments can improve the sicca symptoms but they are unable to modify the course of of primary Sjogren’s syndrome (pSS). There is evidence for a critical role of B cells in the pathogenesis of pSS. Both open labelled and small controlled studies suggested the efficacy of Rituximab (RTX) in specific subgroups of pSS.
Objectives We conducted a multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy of RTX in a large group of patients with active primary Sjögren’s syndrome (pSS).
Methods 122 Patients were assigned to receive either RTX infusions (1g) or placebo (P) at weeks 0 and 2. They were followed up for 24 weeks. All patients fulfilled the new American-European Consensus Group criteria for pSS, had an active disease as assessed by mean values of the 2 highest visual analog scales (VAS) ≥50 evaluating dryness, pain, fatigue and global (disease activity assessed by the patient), and had either a recent (less than 10 years since first clinical sign) and a biologically active pSS [Auto antibodies (SSA or RF) or cryoglobulinaemia, or hypergammaglobulinaemia, or high level of beta 2-microglobulinemia or hypo-complementaemia] or at least one extra-glandular manifestation. The primary end point was an improvement of at least a 30 mm on 2 of 4 VAS between weeks 0 and 24. Secondary end points included values on each VAS separately, the number of tender and swollen joints, the basal salivary flow rate, Schirmer test, the focus score on labial salivary gland biopsy, biological and extra glandular improvement evaluated from baseline to week 24.
Results 24 of 122 patients (19.5%) had a recent pSS without systemic symptoms, 67 (54.9%) had a recent pSS with systemic signs and 31 (25.4%) had a chronic systemic pSS. Concerning systemic manifestations, 33 (28%) had pulmonary involvement, 63 (53%) articular involvement and 34 (28.5%) parotidomegaly. 113 patients had an evaluation at week 24. 11/53 (20.7%) patients receiving P and 13/60 (21.7%) treated with RTX had a favourable overall response (P=0.9). The 30 points VAS improvement for fatigue and sicca were numerically better in the RTX than in the P group [11/60 (18%) vs 5/53 (9%) (p: 0.16) and 15/60 (25%) vs 6/53 (11%) (p:0.06), respectively] but the differences did not reach significance. 9/54 (16.7%) and 9/61 (14.7%) were considered as improved by physicians in P and RTX group, respectively. The two groups did not differ in term of salivary unstimulated flow rate improvement in both recent and chronic pSS.
Conclusions This randomized, double blind, placebo controlled study suggest that the efficacy of RTX is not sufficient enough to allow its prescription in a large population of pSS. Further studies are needed to select which subgroups may justify this treatment.
Disclosure of Interest V. Devauchelle-Pensec Speakers Bureau: Roche, X. Mariette Consultant for: Roche, Speakers Bureau: Roche, S. Jousse-Joulin: None Declared, J.-M. Berthelot: None Declared, A. Perdriger: None Declared, E. Hachulla Consultant for: Roche, Speakers Bureau: Roche, X. Puéchal: None Declared, V. Le Guern: None Declared, J. Sibilia Consultant for: Roche, Speakers Bureau: Roche, J.-E. Gottenberg: None Declared, L. Chiche: None Declared, V. Goeb Speakers Bureau: Roche, G. Hayem: None Declared, J. Morel Consultant for: Roche, Speakers Bureau: Roche, C. Zarnitsky Speakers Bureau: Roche, J.-J. Dubost: None Declared, J.-O. Pers: None Declared, E. Nowak: None Declared, A. Saraux Consultant for: Roche, Speakers Bureau: Roche