The aim of this study was to evaluate the safety and efficacy of RTX in systemic symptoms of pSS. To our knowledge, no published study has focused on the effect of RTX on systemic features of pSS. RTX has been evaluated for pSS‐associated lymphoma and in 15 patients with early disease in a recent phase‐II trial, in which only one patient showed systemic involvement (table 3).9,11,12,13,14,15,16,17,18,19,20
As there is little published experience regarding RTX in pSS, the tolerability of this treatment and the clinical benefit obtained are noteworthy, despite the retrospective design of the study.
Table 3Efficacy and indications of rituximab reported in our and previously published studies
This study confirms the efficacy of RTX for lymphoma alone or with a cyclophosphamide, doxorubicin, vincristine, and a prednisone regimen, and shows its efficacy for other systemic features of pSS (82%). In accordance with the results obtained for rheumatoid arthritis,21
RTX induced clinical improvement in all patients with refractory polysynovitis. RTX was effective for pSS in patients with purpura and ulcerations associated with mixed cryoglobulinaemia, as shown for hepatitis C‐associated mixed cryogobulinaemia.22,23
RTX also had some efficacy in the patient with pSS‐related peripheral nerve involvement without cryoglobulinaemia. Finally, it allowed for sustained remission of renal and pulmonary involvement in patients 1 and 2, respectively.
In our study, RTX was effective in reducing the use of corticosteroids in patients with pSS, as shown in other autoimmune diseases.9,22
The efficacy of RTX for sicca symptoms was rather limited. Interestingly, in a recent study, no improvement in objective parameters was reported in patients with low residual salivary flow and long disease duration, and conversely, in patients with early pSS, a high rate (64.3%) of objective improvement was observed. If dryness results from glandular damage rather than disease activity, RTX given in later stages of the disease, as in our patients, might be insufficient to restore glandular function.
Immediate infusion‐related reactions were observed in only one patient. Such reactions are well described and occur in approximately 30% of patients with rheumatoid arthritis during the first infusion of RTX and in 10% after the remaining infusions.21,24,25
Serum sickness reaction is a rare complication and has been described in only 14 other cases of patients with autoimmune diseases.18,26,27,28,29,30
Regarding the heterogeneous presentation of this complication in the literature, some cases of supposed serum sickness reaction could be merely delayed RTX infusion‐related reactions rather than “authentic” serum sickness diseases. Among our three patients who experienced delayed infusion‐related reactions, one patient did not present with a serum sickness reaction: patient 1, who was re‐treated with no recurrence of delayed RTX infusion‐related reaction. Moreover, she did not develop HACAs. Conversely, the development of HACAs supports the diagnosis of a true serum sickness reaction in patient 3, and might also have impaired B cell depletion and efficacy of RTX in this patient.
For most of our patients, the level of biomarkers of B cell activation, such as rheumatoid factor, β2‐microglobulin, IgG and γ‐globulin, decreased after RTX treatment and increased before clinical relapse (fig 1). The increase in serum BAFF level after RTX treatment was an unanticipated and interesting result. Identical findings have been described recently in patients with rheumatoid arthritis treated with RTX.31
The increase in BAFF level might be the result of depletion of B cells, which are the major source of BAFF receptors, leading to the inability of BAFF to target its receptors. BAFF increase may also represent a feedback mechanism to maximise the proliferation and survival of B cells back to normal levels. A prospective study of additional patients is now required to investigate these hypotheses.
In conclusion, the present study shows the efficacy of RTX for systemic features and glandular swelling in pSS. In addition, RTX allowed for a marked reduction in corticosteroid use. These results illustrate the potential interest of RTX treatment for a disease, often refractory to other immunosuppressive agents. Further controlled trials are now required to confirm the efficacy of RTX in pSS.