COPENHAGEN, Denmark—A group of studies reported at the 2009 Congress of the European League Against Rheumatism (EULAR) adds considerable evidence that rituximab (Rituxan^®, Genentech) is both safe and effective for repeat and/or long-term treatment of rheumatoid arthritis (RA) and suggests that other B-cell depleters, such as Trubion's TRU-015, will also be effective.^1-6

Rituximab often works on second try in initial non-responders

Edward Vital, MD, and colleagues from the University of Leeds, UK, reported that 72% of RA patients who do not respond to initial treatment with rituximab can be successfully re-treated with a second course of rituximab after 6 months.¹

Non-responders had significantly higher numbers of memoryand preplasma cells at baseline, as well as more numerous synovial B cells. After the initial infusion of rituximab, 92% of non-responders had persistent circulating B-lineage cells compared to 48% of responders.

The second infusion of rituximab raised the proportion of non-responders with complete depletion from 8% to 40%. Six months later these patients had a significant improvement in DAS28 compared to either the baseline before the second infusion or the original baseline, 68% of patients had a moderate or better EULAR response, and 37% had a good response.

“High baseline synovial plasma and circulating preplasma cell numbers predict incomplete depletion after rituximab and non-response. Retreatment of non-responders with a second cycle of rituximab before circulating preplasma cells return to baseline levels enhances B cell depletion and results in better clinical responses, with 68% significantly improving. This is a valuable treatment option for patients that have exhausted all other available therapies. Non-responding patients should be re-treated,” Dr. Vital concluded.

In other rituximab studies:

• Tak et al reported that in methotrexate-naive patients with early active RA a combination of rituximab and methotrexate was significantly better than methotrexate alone at improving clinical outcomes (including major clinical response) and inhibiting joint damage, but did not change radiological outcomes.² This study was a randomized active-comparator placebo-controlled trial.
• Bingham et al reported data from the SIERRA trial showing that RA patients treated with rituximab have normal responses to tetanus toxoid and preserved DTH response, but reduced responses to pneumococcal polysaccharide and neoantigen vaccination.³ “This suggests that polysaccharide and primary immunizations should be considered before rituximab infusions to maximize response,” Dr. Bingham said.
• Wendler et al reported interim data from the German RTX Treatment of Active Rheumatoid Arthritis in Daily Practice Trial, which showed similar disease activity scale (DAS) responses in patients treated with rituximab alone, rituximab+leflunomide, and rituximab+methotrexate, but better Health Assessment Questionnaire (HAQ) responses in those treated with rituximab+leflunomide than with rituximab+methotrexate.⁴
• van Vollenhoven et al reported long-term follow-up data from RA clinical trials and the re-treatment population confirming that rituximab remained well-tolerated for up to 5 courses, with a stable safety profile.⁵

Finally, in related work on B-cell depletion, Stromatt et al reported phase 2B data for the new agent TRU-015 (Trubion), which showed that repeat dosing was generally well tolerated, with pharmacodynamic and pharmacokinetic profiles comparable to initial treatment, and with durable beneficial effects on rheumatoid arthritis disease activity.⁶

References

1. Vital EM, Dass S, Buch MH, et al. How to manage non-response to rituximab? Predictors and outcome of retreatment provide data for a treatment algorithm. Presented at the 2009 EULAR meeting, Copenhagen, June 12, 2009. Presentation no. OP-0027.
2. Tak PP, Rigby W,  Rubbert A, et al. Inhibition of joint damage and improved clinical outcomes with a combination of rituximab (RTX) and methotrexate (MTX) in patients (PTS) with early active rheumatoid arthritis (RA) who are naive to MTX: a randomised active comparator placebo-controlled trial. Presented at the 2009 EULAR meeting, Copenhagen, June 12, 2009. Presentation no. OP-0022.
3. Bingham CO, Looney RJ, Deodhar A, et al. Immunization responses in rheumatoid arthritis patients treated with rituximab: results from a controlled clinical trial (SIERRA). Presented at the 2009 EULAR meeting, Copenhagen, June 12, 2009.
4. Wendler J, Soerensen H, Tony H, et al. Effectiveness and safety of rituximab (RTX)-monotherapy compared to RTX-combination therapy with methotrexate (MTX) or leflunomide (LEF) IN THE GERMAN RTX treatment of active rheumatoid arthritis (RA) in daily practice trial. Presented at the 2009 EULAR meeting, Copenhagen, June 12, 2009. Presentation no. OP-0025.
5. van Vollenhoven RF, Emery P, Bingham CO, et al. Long-term safety of rituximab: follow-up of the RA clinical trials and re-treatment population. Presented at the 2009 EULAR meeting, Copenhagen, June 12, 2009. Presentation no. OP-0026.
6. Stromatt S, Chopiak V, Dvoretskiy L, et al. TRU-015 improves rheumatoid arthritis disease activity after first course of retreatment following phase 2B study. Presented at: 2009 EULAR meeting, Copenhagen, June 12, 2009. Presentation no. OP-0028.