Rituximab in autoimmune diseases: off-label use in clinical practice

Janis Kelly

January 24, 2005

Jan 24, 2005

Paris, France - Although the B-cell depleter rituximab (Rituxan, MabThera; Genentech/IDEC) is not yet marketed for use in the treatment of autoimmune diseases, it is already being used off label in routine clinical practice, a French survey has found. Dr Xavier Mariette (Service de Rhumatologie Hopital Bicetre, Le Kremlin-Bicetre, France) and colleagues report on rituximab treatment of 43 patients identified in a survey of 866 rheumatologists and internists published online December 15, 2004 in the Annals of the Rheumatic Diseases [ 1 ].

Our main findings were that rituximab had considerable efficacy in rheumatoid arthritis, systemic lupus erythematosus, primary Sjogren's syndrome, vasculitis, and some other inflammatory arthritides and was relatively well tolerated in these patients.

"Our main findings were that rituximab had considerable efficacy in rheumatoid arthritis [RA], systemic lupus erythematosus [SLE], primary Sjogren's syndrome [pSS], vasculitis, and some other inflammatory arthritides and was relatively well tolerated in these patients," Mariette tells rheuma wire .

The researchers were surprised at how frequently rituximab was being used in patients with systemic autoimmune diseases. "Despite the absence of marketing authorization in these indications and taking into account that the drug is available for lymphoma and well tolerated, leader clinicians in some teaching hospitals have used it in cases of severe refractory autoimmune diseases, but with the agreement of the local committees on prescription of new drugs, in most cases," Mariette says.

Retrospective study finds widespread use

This retrospective study found that rituximab was prescribed for lymphoma in 2 patients with RA and 2 with pSS and because the autoimmune disease was refractory in the other 39 cases.

Efficacy was assessed by Disease Activity Score in 28 joints (DAS28) in RA, the SLE Disease Activity Index (SLEDAI) in SLE, and the clinician's estimate of a decrease of 50% or more in disease activity in other autoimmune diseases.

Rituximab was judged effective in 11 of 14 RA patients, 9 of 13 SLE patients, 5 of 6 pSS patients, 2 of 5 systemic vasculitis patients, and 3 of 5 patients with other autoimmune diseases. Responders were able to decrease daily corticosteroid intake by a mean 9.5 mg/day.

The researchers judged that tolerance of rituximab was good. There were 11 adverse events in 10 patients, in 6 of whom treatment was discontinued due to adverse effects.

Mariette says that trying an empirical course of rituximab might be a reasonable approach in RA patients who have not responded to TNF inhibitors, in severe refractory lupus, in severe Sjogren's with systemic involvement, or in antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis refractory to cyclophosphamide.

"Controlled trials [of rituximab] are in process in RA and in ANCA-associated vasculitis. They are going to start in lupus in the next few weeks. Our group is working to begin a controlled study in Sjogren's, I hope before the end of the year," Mariette says.

Rituximab not effective in Felty's syndrome

Rituximab was not effective in 2 patientswith Felty's syndrome, Dr Jean Sibilia (Hopital de Hautepierre, Strasbourg, France) reports in the February 2005 issue of the Annals of the Rheumatic Diseases [ 2 ]. The patients had a duration of RA of 6 and 11 years and remained active despite the use of corticoids plus sulfasalazine or sulfasalazine/methotrexate. Patients were treated with rituximab 375 mg/m 2 once weekly for 4 weeks, along with prednisone (15-25 mg/day) in both patients and methotrexate in 1 of them.

At a follow-up duration of 6 months, rituximab controlled RA activity in 1 patient but had no effect on the neutrophil counts or infection rates associated with Felty's syndrome.

The authors speculate that this lack of efficacy might be due to rituximab's inability to bind to plasma cells.


  1. Gottenberg JE, Guillevin L, Lambotte O, et al. Tolerance and short-term efficacy of rituximab in 43 patients with systemic autoimmune diseases. Ann Rheum Dis 2004; DOI:10.1135/ard.2004.029694.

  2. Sordet C, Gottenberg JE, Hellmich B, et al. Lack of efficacy of rituximab in Felty's syndrome. Ann Rheum Dis 2005; 64:332-333.



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