We present the first controlled pilot trial of MPS treatment in patients with pSS. Our study shows that MPS can improve symptoms and laboratory findings in patients with active pSS. The optimum systemic treatment of pSS is still unclear. Although no controlled study has been performed so far, MPA was suggested as sole or adjuvant treatment for pSS in a recent review [19
We found a significant reduction of ocular dryness assessed by a VAS. In accordance with this finding, the daily demand for artificial teardrops decreased significantly in our patients. On the other hand, no improvement in the salivary and lachrymal gland functions in our cohort was observed. It should be noted, however, that we observed a remarkable improvement of glandular function in two patients with a disease duration of less than 3 years, possibly due to recovery of the glandular tissue. It has been reported that regeneration of glandular tissue and recovery of glandular function can occur only in patients with residual glandular function [20
]. Lack of improvement in the other patients might be due to irreversible damage of the glandular tissue after a long disease duration. Improvement of salivary gland function has been reported in patients with early pSS after treatment with rituximab, an anti-CD20 monoclonal antibody. These observations emphasize the need for an earlier and more aggressive treatment in pSS patients with short disease duration [21
Mycophenolate has been used in systemic vasculitis [22
]. In the one patient with vasculitis, a reduction that has been reported previously in a pSS patient treated with MMF was observed [12
]. Thus, MPA-containing compounds might be useful in this systemic manifestation.
We found a significant reduction of gamma globulins during treatment. Hypergammaglobulinemia has been proposed as a suitable target for therapy and as a primary outcome measure for the evaluation of the pSS treatment [23
]. It has been suggested that reduction of B-cell hyperactivity with immunosuppressants might be the best prevention of lymphoproliferation in pSS [24
]. As a low level of C4 has been associated with an increased risk of developing lymphoproliferative disease [25
] and as our data show an increase of C3 and C4 levels in patients treated with MPS, this drug may be essentially beneficial in this context.
Furthermore, we found a significant reduction of IgM after 24 weeks, whereas no substantial reduction of IgG or IgA was detectable. In addition, a reduction of IgM-RF during the treatment was observed. Treatment with rituximab has also been accompanied by a decrease of IgM and IgM-RF in pSS patients without changes in IgG or IgA levels [21
We found no changes in anti-SSA/anti-SSB antibody titers. These antibodies are relatively stable over time in individual patients and thus are not suggested as an outcome measure of disease activity [27
]. Likewise, in pSS patients receiving B-cell-depleting agents (for example, rituximab or epratuzumab), no changes in anti-SSA and anti-SSB antibodies were detected [26
We observed an increase of leukocytes/neutrophils during MPS treatment. Leukopenia is one of the most frequent extraglandular manifestations of the disease and is probably mediated by antineutrophil antibodies [29
]. Leukopenia in pSS has been shown to be reversed by immunosuppressive treatment with corticosteroids or hydroxychloroquine [29
]. Our data show that MPS also might be effective in treating pSS-associated leukopenia.
Patients of our cohort showed significant improvement in the general health and role emotional domains of the SF-36. A trend toward a significant increase of the mental component summary score was observed. This indicates an improvement in psychological distress, social disability due to emotional problems, and self-related health [16
The overall tolerability of MPS in patients with pSS was acceptable. The most frequent AE was mild GI discomfort. GI discomfort has been reported as the most common AE leading to discontinuation of therapy in transplant recipients [6
]. In SLE patients treated with MMF, GI-related symptoms are common as well. The symptoms tend to be mild and can improve with dose reduction [8
]. In transplant recipients treated with enteric-coated MPS, less severe GI AEs have been observed as compared with MMF [30
One of our patients, after 15 days of treatment, developed pneumonia that caused hospitalization. Although the patient received only a fairly low dose of 720 mg MPS per day for only 2 weeks, the event was possibly related to the study drug. All in all, however, compared with studies with transplant recipients [6
], the incidence rate of infections was low in the present study.