Rituximab treatment in patients with primary Sjögren's syndrome: An open‐label phase II study

Abstract

Objective. To investigate the safety and efficacy of B cell depletion treatment of patients with active primary Sjögren's syndrome of short duration (early primary SS) and patients with primary SS and mucosaassociated lymphoid tissue (MALT)-type lymphoma (MALT/primary SS).Methods. Fifteen patients with primary SS were included in this phase II trial. Inclusion criteria for the early primary SS group were B cell hyperactivity (IgG >15 gm/liter), presence of autoantibodies (IgM rheumatoid factor, anti-SSA/SSB), and short disease duration (<4 years). Inclusion criteria for the MALT/ primary SS group were primary SS and an associated MALT-type lymphoma (Ann Arbor stage IE) localized in the parotid gland. Patients were treated with 4 infusions of rituximab (375 mg/m 2 ) given weekly after pretreatment with prednisone (25 mg) and clemastine. Patients were evaluated, using immunologic, salivary/ lacrimal function, and subjective parameters, at baseline and at 5 and 12 weeks after the first infusion.Results. Significant improvement of subjective symptoms and an increase in salivary gland function was observed in patients with residual salivary gland function. Immunologic analysis showed a rapid decrease of peripheral B cells and stable levels of IgG. Human antichimeric antibodies (HACAs) developed in 4 of 15 patients (27%), all with early primary SS. Three of these patients developed a serum sickness-like disorder. Of the 7 patients with MALT/primary SS, complete remission was achieved in 3, and disease was stable in 3 and progressive in 1.Conclusion. Findings of this phase II study suggest that rituximab is effective in the treatment of primary SS. The high incidence of HACAs and associated side effects observed in this study needs further evaluation.

The value of rituximab treatment in primary Sjögren's syndrome

“…β2-microglobulin levels show a 'delayed' drop at 16 weeks after treatment [8,12], which was not seen at 6 or 12 weeks after rituximab treatment [8,11]. Serum immunoglobulin free light chains (FLCs) are also affected by rituximab and decrease significantly from week 5 up to week 48 after treatment (unpublished data), in line with findings in RA [19].…”

“…In other trials, including the TEARS trial, no effect on UWS was observed [6,8,11,15]. Although the mean baseline UWS in the TEARS trial was comparable to the study of Meijer et al, the standard deviation was twice as high, which may influence the power of their analysis.…”

“…Pijpe et al showed that rituximab improved stimulated submandibular/sublingual salivary flow only in patients with residual salivary gland function at baseline (SWS N 0.10 ml/min) [11]. Similarly, in the RCT by Meijer et al only patients with a SWS ≥ 0.15 ml/min were included, and SWS was significantly increased in the rituximab group, while it deteriorated in the placebo group [4].…”

“…Measurement of the epithelial integrity of the ocular conjunctiva by rose Bengal or lissamin green, and cornea by fluorescein staining is more reliable to evaluate keratoconjunctivitis sicca [43]. Interestingly, studies using these ocular surface staining methods did show improvement after treatment [4,11]. This improvement may be caused by effects of rituximab on tear gland morphology and function, composition of tear fluid, as well as effects on the inflammatory microenvironment of the ocular surface.…”

Immunogénicité de protéines d’intérêt thérapeutique

“…Une telle dissociation est également observée avec l'Acm chimérique anti-CD20 rituximab (➜). Lorsqu'il est administré à des patients atteints de leucémie lymphoïde chronique B, il n'entraîne pas de réponse immune [13,14] ; au contraire 65 % des patients atteints de lupus érythémateux disséminé et 27 % de ceux atteints de polyarthrite rhumatoïde traités par ce même rituximab développent des ADA [15,16]. Quant à l'adalimumab, un anticorps complètement humain, il induit un taux de réponses immunes de 1 à 12 % dans la polyarthrite rhumatoïde [17,18].…”