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While rituximab has proven to be an effective treatment for rheumatoid arthritis, it has failed to meet its primary endpoints in clinical trials for systemic lupus erythematosus (SLE). But now, an observational study suggests that rituximab could be effective as maintenance therapy in difficult SLE cases.
While rituximab has proven to be an effective treatment for rheumatoid arthritis, it has failed to meet its primary endpoints in clinical trials for systemic lupus erythematosus (SLE). But now, an observational study published online May 18 in Arthritis and Rheumatology, suggests that rituximab could be effective as maintenance therapy in difficult SLE cases.
The study, which was led by Federico Alberici M.D., Ph.D., of the University of Milano in Italy, included 147 SLE patients. At six months, treatment failed in 27 percent of patients. Of 80 patients on maintenance therapy over 24.5 months, 85 relapsed. But by the last course of rituximab, 84 percent were in remission. During maintenance treatment, 35 percent of patients never flared.
SYSTEMIC LUPUS ERYTHEMATOSUS
Systemic lupus erythematosus (SLE) is a complex autoimmune disease affecting a wide range of organ systems. Autoimmunity by definition is the attack on ones own tissues by ones own immune system and in particular B-cell hyperactivity. Rituximab, a monoclonal antibody, works by depleting the number of autoimmune B-cells. While having shown promise in other autoimmune disorders, it has failed to meet primary endpoints in randomized controlled trials.
The goal for treatment of SLE is sustained remission and maintenance of that remission. While limited rigorous evidence exists supporting the use of rituximab for systemic lupus erythematosus, it is often employed, with some success, in relapsing and refractory cases. This discrepancy may be explained by the presence of factors predicting the success or failure of rituximab therapy for systemic lupus erythematosus.
While some indicators have been associated with prognosis when treated with rituximab no large studies looking at retreating systemic lupus erythematosus patients with rituximab as maintenance to prevent relapses have been performed. The authors sought to explore the efficacy and safety of rituximab in systemic lupus erythematosus while determining what prognostic factors influence responses to the treatment.
The authors conducted a multicenter, observational study of 147 patients with systemic lupus erythematosus. Patients were either treated with a single course of rituximab or with maintenance treatment, which consisted of at lease three single courses of treatment.
• At six months, 27 percent of patients experienced treatment failure. The risk of treatment failure was reduced if patients had a low number of prior immunosuppressive treatments and low C4 complement levels (p=0.034 and p=0.008 respectively).
• 85 relapses occurred in the maintenance group which were mainly musculoskeletal and occurred at a rate of 1.06 per patient. After the last dose of rituximab in the maintenance group, 84 percent were in remission with 35 percent never having a relapse or significant damage accrual.
• Having active joint disease at the time of the first rituximab course was correlated with a higher risk for flare during maintenance treatment (p=0.010).
• When the maintenance period had ended, there was no difference in relapse free survival between the single course treatment group and the maintenance group (p=0.72).
• 109 severe adverse events occurred in 54 patients (24 in the maintenance group and 53 in the single course group). The cumulative number and the proportions of the events did not differ between the two groups. One patient died of neutorpenic sepsis.
• Damage accrual continued even in the maintenance group but was lower in the sustained responder subgroup (the 35 percent who had no flares).
• Anti-DNA levels decreased after the first rituximab dose and fell to normal levels during maintenance. CD19+ B-cells were undetectable in 76 percent of patients by the second rituximab course.
Take-Home Points for Clinicians and Final Thoughts
The overall positive response seen in this study supports the role of rituximab treatment in difficult systemic lupus erythematosus (SLE) cases. Rituximab treatment is particularly helpful in patients with low C4 levels, with more severe disease, and who have taken fewer immunosuppressive drugs in the past.
With relapses being difficult to predict, a rituximab maintenance course delivered at fixed intervals may be the best option. Rituximab maintenance may also allow the clinician to reduce other immunosuppressive drugs like corticosteroids.
While disease control was improved in this study, damage accumulated at the same rate as before the maintenance phase. This effect may have been due to the generally higher baseline disease activity of these patients.
Clinicians should be extremely vigilant for adverse events during rituximab treatment with a particular eye for infections and neutropenia.
The results of this study were far from definitive. The fact that they still support the use of rituximab maintenance therapy in SLE underscores the dire situation lupus patients are in when disease activity is high and refractory. This regimen should be considered in SLE patients with severe disease, high likelihood of flares, and when other options have failed.
Matthias A. Cassia, Federico Alberici, Rachel B. Jones, et al. “Rituximab as maintenance treatment for systemic Lupus Erythematosus: a multicentre observational study of 147 patients.”Arthritis and Rheumatology. Published online May 18, 2019. DOI:10.1002/art.40932