We previously reported that B cell depletion therapy with rituximab (4 weekly infusions of 375 mg/m², premedication: 25 mg prednisolone intravenously) in eight patients with early primary Sjögren syndrome (pSS) and seven patients with mucosa-associated lymphatic tissue (MALT)/pSS was effective in reducing subjective and objective symptoms after 12 weeks of follow-up.1 Three patients with early pSS developed serum sickness-like disease, of whom one patient declined to further participate. The MALT component of six of the seven patients with MALT/pSS was initially effectively treated with rituximab, one of these six patients was successfully retreated 9 months after the first treatment and all six patients are still in remission of MALT >2 years after treatment. Therefore, we focused the present work on the extended follow-up and retreatment of the patients with early pSS. For seven of the eight patients with early pSS, 48-week follow-up data were available. In addition, five patients, who did not develop serum sickness and in whom symptoms returned, were retreated with four infusions of rituximab and followed for another 48 weeks. Return of symptoms included decrease of salivary flow, increase of rheumatoid factor and return of B cells and subjective symptoms.

FIRST COURSE OF RITUXIMAB (N = 7)

Depletion of peripheral B cells was complete 5 weeks after onset of therapy. By 36 weeks, median peripheral B cell numbers had returned, although levels were still low in some patients. Stimulated submandibular/sublingual salivary flow showed a significant increase at week 12, followed by a gradual decline to just above baseline at 48 weeks. Similarly, a significant improvement of most of the visual analogue scale (VAS) scores for dry mouth and most domains of the Multidimensional Fatigue Inventory (MFI) was observed, followed by a gradual decline to near baseline.

RETREATMENT WITH RITUXIMAB (N = 5, FIG 1)

Retreatment had a significant effect on B cells, levels of IgM-rheumatoid factor (RF) and stimulated submandibular/sublingual salivary flow similar to the effects of the first course. VAS scores for dry mouth, MFI scores for general fatigue and Short-Form 36 (SF-36) questionnaire scores for physical functioning improved significantly too. For the other subjective symptoms a similar trend towards improvement was seen as after the first course. Again, almost all variables had returned to baseline 6–9 months after retreatment. One patient developed serum sickness-like disease (purpura, arthralgia, myalgia) after the second rituximab infusion during the retreatment course. Rituximab treatment was stopped, pain relief (non-steroidal anti-inflammatory drugs (NSAIDs)) and 120 mg methylprednisolone was given once. The patient recovered completely.

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Figure 1 Increase and decrease (mean values of five patients with primary Sjögren syndrome (pSS)) in stimulated submandibular/sublingual flow rate, IgM-rheumatoid factor (RF), B cells, visual analogue scale (VAS) score for dry mouth during the night and Multidimensional Fatigue Inventory (MFI) score for fatigue following rituximab (re)treatment (baseline is 100%). Mean (SD) baseline values (week 0 first treatment) were: stimulated submandibular/sublingual flow rate 0.09 (0.07) ml/min, IgM-RF 339 (329) lU/ml, B cells 0.19 (0.09) 10⁹/litre, VAS score for dry mouth during the night 85 (12), MFI score for fatigue 16 (3). • Stimulated submandibular/sublingual salivary flow rate. ♦ IgM-RF. * B cells. ▾ VAS score for dry mouth during the night. ▾ MFI score for fatigue.

CONCLUSIONS

Rituximab appeared to be effective for at least 6–9 months in patients with pSS with active disease, improving subjective and objective symptoms. Development of serum sickness-like disorder in a substantial number of patients with pSS indicates that higher doses of corticosteroids might be needed during treatment. Retreatment resulted in a good clinical response in patients with pSS comparable to the response in patients with rheumatoid arthritis (RA)2 and patients with systemic lupus erythaematosus (SLE).3 Based on these promising results, one might consider maintenance treatment. The best approach to and timing of maintenance treatment has, however, to be studied in future trials. Furthermore, attention has to be paid to among others the possibility of development of humoral immunodeficiency related to repeated treatment.2