Abstract 1102: Rituximab Therapy for Primary Sjögren's Syndrome (pSS): An Open-Label Trial
Thomas Grader-Beck
Authors:
E. St. Clair, M. Levesque, N. Luning Prak, F. B. Vivino, C. Alappatt, D. Wallace, J. Wedgwood, P. Cohen
Background
To explore the safety, clinical efficacy, and biological activity of rituximab therapy for pSS.
Methods:
The study was an open-label trial in which 12 subjects with pSS were treated with two infusions of 1 g rituximab given two weeks apart, with follow-up for 52 weeks. Prior to each infusion, subjects received 100 mg of IV methylprednisolone and 50 mg of diphenyhydramine. Eligible subjects were 18 to 75 years old, met the American-European Consensus Group criteria for the classification of pSS, and had 1 or more severe disease manifestations, including fatigue (> 50 mm on a VAS scale), joint pain (> 50 mm on a VAS scale), parotid gland swelling, peripheral neuropathy, interstitial lung disease, and purpura. Subjects were allowed to continue hydroxychloroquine or prednisone (≤ 10 mg/day) therapy, but not other immunosuppressive drugs. Lymphocyte immunophenotyping was performed using flow cytometry. Changes in VAS scores (100 mm scale) were analyzed using the Wilcoxon sign rank test. The preliminary results described herein are for all subjects through week 26 of follow-up.
Results:
The 12 subjects with pSS were all female and had a median age of 51 years old (range 34-69), with a median disease duration of 6.5 years. Of the 12 eligible subjects at screening, 10 and 9 had VAS scores of > 50 mm for fatigue and joint pain, respectively; 3 had severe parotid gland swelling; 4 had peripheral neuropathy, 1 had interstitial lung disease, and 1 had purpura. All of the subjects had rapid depletion of circulating CD19+ B cells following rituximab therapy, with expected nadirs for all subjects of < 5/μL. There was 1 serious adverse event, a severe local reaction with fever related to immunization at week 26 with Pneumovax. Serum sickness was not observed in any subjects. A significant decrease was observed between baseline and week 26 for both the physician global (median change -29.0 mm; p=0.0068) and subject global (median change -9.0 mm; p=0.0068) assessment VAS scores. In addition, we found reductions over this period in the VAS scores for fatigue (median change -19.0 mm; p=0.019) and joint pain (median change -4.0 mm; p=0.019). No significant changes were observed between baseline and week 26 for most of the ocular and oral symptoms of dryness and the unstimulated (median change 0.02 mL/min; p=0.287) and stimulated (median change 0.01 mL/min; p=0.718) salivary flow rates.
Conclusions:
Rituximab therapy produced rapid depletion of circulating B cells in patients with pSS, without serious drug-related toxicity. Larger, placebo-controlled trials will be needed to determine if rituximab therapy has significant clinical benefits for this disease.
Editorial Comment:
None of the two studies reporting on clinical outcomes detected a striking effect on disease activity. Improvement was reported by changes in the VAS score for fatigue and joint pain as well as the global assessment physician and patient VAS score in the St.Clair et al. study. These results are in contrast to some earlier studies that reported significant improvement of salivary gland flow. The patients in the St. Clair et al. study had a median disease duration of 6.5 years. It is possible that many of the patients already suffered from irreversible structural damage before initiation of therapy. Salivary gland biopsies prior to initiation of therapy may have shed better light on the potential efficacy of Rituximab for salivary gland dysfunction. While Rituximab may represent a promising therapy for patients with Sjögren’s syndrome, it will be difficult to demonstrate this effect without reliable and consistent markers to measure disease activity.
