BOSTON, Massachusetts—Rituximab (RTX) (Rituxan®, Genentech, Inc) can be given repeatedly and can produce remissions even in some patients with DMARD-resistant rheumatoid arthritis (RA), it is effective even without methotrexate (MTX), it offers hope in some cases of pediatric systemic lupus erythematosus (SLE), and it is being studied in Sjögren's syndrome, researchers reported at the American College of Rheumatology 2007 meeting.

Repeated RTX makes remission a possibility even for treatment-resistant RA

The researchers, led by Paul Emery, MD, analyzed data from an ongoing open-label extension of two phase II studies comprising 94 patients who had been exposed to at least three courses of RTX. Dr. Emery reported on the 57 patients who had reached at least 24 weeks of follow-up after the third course of treatment, at which point, 65% of patients had ACR20 responses, 33% had ACR50, and 12% had ACR70. Fourteen percent were in remission (DAS28 <2.6). The mean DAS28 change from baseline was -2.72.

"Our results show that repeated courses of rituximab produce sustained efficacy in patients with active RA and a previous inadequate response to DMARDs," Dr. Emery said.

RTX monotherapy a possibility in some cases

Owczarczyk et al reported that in RA patients for whom DMARDs have been ineffective or who cannot tolerate concomitant DMARDs, RTX monotherapy is as effective as standard RTX and MTX combination therapy.2 All patients received  two 1-g infusions of RTX. The researchers analyzed DAS28, serum rheumatoid factor, and anti-CCP levels at baseline and week 16 following the first RTX infusion in 15 patients on RTX monotherapy and in 15 on RTX with MTX. They also used flow cytometry to measure B-cell depletion.

"Our results show that repeated courses of rituximab produce sustained efficacy in patients with active RA and a previous inadequate response to DMARDs."—Paul Emery, MD.
Clinical responses were similar in both groups. B-cell depletion and the kinetics of B-cell repopulation were also similar. "In summary, our data suggest that rituximab monotherapy can be used effectively in patients who are unable to receive adjuvant DMARD therapy," the researchers concluded.

Single RTX course produces durable responses in pediatric SLE

Kumar et al reported that a single course of RTX produced complete remissions in all five pediatric lupus patients who had autoimmune thrombocytopenia (AITP) and in all three pediatric lupus patients who had autoimmune hemolytic anemia (AIHA).3

AITP in two children flared at weeks 48 and 68, respectively, and the children were re-treated with a second course of rituximab. In both cases partial B-cell reconstitution had occurred before the flare. The other three children remained in remission at weeks 8, 76, and 88. All patients with AIHA remained in complete remission at weeks 44, 66, and 76 of follow-up, and immunosuppressive medications were decreased in all patients.

"B-cell depletion therapy with rituximab is an efficacious and safe treatment for AITP and AIHA in pediatric SLE. The majority of children achieved complete remission for at least 9 months. Despite prolonged effect on B-cell numbers and function, no serious infections were observed," Dr. Kumar reported.

Early tests of RTX in Sjögren's syndrome

Dass et al reported a pilot study of RTX in primary Sjögren's syndrome, for which there is currently no effective therapy.4 Nine patients were randomized to RTX, nine to placebo. The authors reported a trend to greater improvement in the primary outcome measure (fatigue) in the RTX group (mean improvement 48.4% (vs 20%, P = NS). The investigators conclude that RTX may improve fatigue and systemic symptoms without influencing IgG levels and that a study with 37 patients per arm would be adequately powered to detect a significant difference in the primary endpoint.

St. Clair et al reported similarly promising results in an open-label trial of RTX in 12 patients with primary Sjögren's syndrome.5 Each patient received two 1-g infusions, with follow-up for 52 weeks. Treatment produced rapid depletion of circulating B-cells without serious drug-related toxicity. Both the physician global and subject global assessment VAS scores decreased significantly between baseline and week 26. There were also reductions in the VAS scores for fatigue (median change -19 mm; P = .019) and joint pain (median change -4 mm; P = .019). There were no significant changes for most of the ocular and oral symptoms of dryness or in the unstimulated or stimulated salivary flow rates.

References
1. Emery P, Furst DE, Ferraccioli G, et al. Repeated treatment courses of rituximab produce sustained efficacy in rheumatoid arthritis patients with an inadequate response to disease-modifying antirheumatic drugs. Presented at: American College of Rheumatology Meeting; November 7-11, 2007; Boston, Mass. Presentation Number: 266.
2. Owczarczyk K, Hellmann M, Roehrs T, et al. Clinical outcome and the kinetics of B-cell depletion in patients with active rheumatoid arthritis receiving rituximab monotherapy in comparison to patients with concomitant MTX. Presented at: American College of Rheumatology Meeting; November 7-11, 2007; Boston, Mass. Presentation Number F82.
3. Kumar S, Benseler S, Silverman E. B-cell depletion for autoimmune thrombocytopenia and autoimmune hemolytic anemia in pediatric systemic lupus erythematosus: a single center experience. Presented at: American College of Rheumatology Meeting; November 7-11, 2007; Boston, Mass. Presentation Number 876.
4. Dass S, Bowman SJ, Vital EM, et al. Safety and efficacy of rituximab in Sjögren's syndrome: results of a randomised, placebo-controlled pilot study. Presented at: American College of Rheumatology Meeting; November 7-11, 2007; Boston, Mass. Presentation Number 1094.
5. St. Clair EW, Levesque MC, Luning-Prak N, et al. Rituximab therapy for primary Sjögren's syndrome (pSS): an open-label trial. Presented at: American College of Rheumatology Meeting; November 7-11, 2007; Boston, Mass. Presentation Number 1102.