Treatment for primary Sjogren's syndrome with the B-cell depleting antibody rituximab (Rituxan) failed to provide statistically significant improvements, despite the increasing evidence for B cells in the pathogenesis of this disorder, French researchers reported.
On the primary outcome measure, decreases of 30 mm on two of four 100-mm visual analog scales measuring various disease domains at 6 months was seen in 23% of patients receiving rituximab and 22% of those given placebo, for a mean difference of 1% (95% CI -16.7-18.7, P=0.91), according to Alain Saraux, MD, PhD, of Hopital de la Cavale Blanche in Brest, and colleagues.
had suggested the possibility of benefits for rituximab in Sjogren's patients. And while 6-month results were nonsignificant in the current study, , with a difference between the treatment and placebo groups of 13.3% (95% CI 0.8-25.8 P=0.036), the researchers reported in the Feb. 18 issue of Annals of Internal Medicine.
"Thus, although our data provide some support for the efficacy of rituximab reported in two previous preliminary studies, the size and duration of the benefit argue against treating [primary Sjogren's syndrome] with rituximab," they wrote.
No systemic treatment has shown efficacy for altering the course of Sjogren's syndrome, an autoimmune disease primarily affecting the exocrine glands, although various disease-modifying agents such as hydroxychloroquine and methotrexate have been used for symptom relief.
To further explore the possible benefits of rituximab seen in earlier trials that measured outcomes such as fatigue and , Saraux and colleagues enrolled 120 patients who had scores of at least 50 on two of four outcomes: fatigue, dryness, pain, and global disease, randomizing them to infusions of 1 g rituximab at baseline and week two, or placebo.
More than 90% of the patients were women. Mean age was 53 and mean time since diagnosis was 5 years.
Mean scores on visual analog scales were approximately 69 for global disease, 54 for pain, 69 for fatigue, and 71 for dryness.
Mean baseline score on the European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (ESSDAI), which evaluates systemic manifestations of the disease, was 10.1 out of a possible 47.
Although benefits were limited on the primary outcome, certain secondary measures, such as fatigue, showed positive effects.
Patients with Sjogren's syndrome report fatigue to be a particularly troublesome symptom, and this was the disease domain with the greatest effect in this study.
At week six, the mean difference between the rituximab and placebo groups for fatigue was 26.6% (95% CI 15.7-37.5, P<0.001), although this decreased to a nonsignificant 9.3% (95% CI -2-20.5, P=0.105) by month six.
Also at week six, significant differences between the rituximab and placebo groups were seen on these physician-rated outcomes:
- Disease activity: 19.1% (95% CI 4.4-33.7, P=0.011)
- Treatment efficacy: 21% (95% CI 9.3-32.7, P=0.001)
- Global score: 8.4% (95% CI 4.2-12.5, P<0.001)
However, these differences had become nonsignificant by 6 months, the researchers reported.
In addition, significant differences weren't found on the ESSDAI or in the percentages of patients who had resolution of joint symptoms or parotid gland swelling.
The lack of apparent effect on the ESSDAI may have reflected the low baseline score on this measure, "and we cannot exclude a better effect of the treatment in more active [primary Sjogren's syndrome]," the investigators noted.
Adverse events occurred at similar rates in the rituximab and placebo groups, although patients receiving the active treatment more often had infusion reactions.
The investigators also observed that a possible explanation for the lack of effect of rituximab in Sjogren's syndrome is that B cells located within target organs, such as the salivary glands in Sjogren's, may not be as susceptible to depletion as those in the wider circulation.
"In conclusion, our data do not support the use of rituximab therapy in many patients with recent-onset or systemic [primary Sjogren's syndrome]," they stated.
A limitation of the study was the possibility that the primary endpoint may not been sufficiently sensitive "to detect clinically important changes in symptoms."
Disclosures
The study was supported by the Programme Hospitalier de Recherche Clinique 2010, and rituximab was supplied without charge by Roche.
The investigators disclosed relevant relationships with Roche, Abbott, Chugain, BMS, Pfizer, and UCB.
Primary Source
Annals of Internal Medicine
Devauchelle-Pensec V, et al "Treatment of primary Sjogren syndrome with rituximab" Ann Intern Med 2014; 160: 233-242.