Elsevier

Autoimmunity Reviews

Volume 10, Issue 2, December 2010, Pages 108-111
Autoimmunity Reviews

Review
The administration of low doses of rituximab followed by hydroxychloroquine, prednisone and low doses of mycophenolate mofetil is an effective therapy in Latin American patients with active systemic lupus erythematosus

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Abstract

Background

In Latin America, the medical attention directed to systemic autoimmune diseases competes with a budget designed to fight poverty, lack of education, etc. In this context, the access to treatments recommended internationally are expensive and limited; therefore, research of methods that make these treatments cheaper is of paramount importance.

Objective

Our objective was to describe the 24-month clinical outcome of patients with active systemic lupus erythematosus (SLE) who received low doses of rituximab (RTX), followed by hydroxychloroquine (HCQ), prednisone and low doses of mycophenolate mofetil (MMF).

Methods

Forty-six patients with active SLE received 500 mg of RTX (together with 500 mg of methylprednisolone as a premedication) administered on two occasions 2 weeks apart, followed by HCQ (200–400 mg/day), prednisone and MMF (500–1000 mg/day) during a 24-month follow-up period. Clinical outcome was assessed using the MEX-SLE Disease Activity Index (MEX-SLEDAI) and serial serologic measurements. Remission was defined as MEX-SLEDAI scores 0–1, mild disease activity 2–5, moderate disease activity 6–9, severe 10–13, and very severe 14 or more.

Results

Disease activity decreased over time with treatment. At baseline, 19 (41.3%) patients had very severe, 16 (34.8%) severe, and 9 (19.6%) moderate disease activity. Improvement on disease activity was detected at 3 months, since 9 (19.6%) patients reached disease remission after this period of time and remission increased to 16 (34.8%) patients at 6 months, 19 (41.3%) at 1 year, and 23 (50%) at 2 years of follow-up (p < 0.0001).

Conclusion

The administration of low doses of RTX followed by HCQ, prednisone and low doses of MMF is an effective therapy in Latin American patients with active SLE.

Introduction

Systemic lupus erythematosus (SLE) is a complex autoimmune condition characterized by many diverse clinical manifestations, with different levels of disease activity and severity. Therapy should be addressed to obtain clinical remission; if this goal is not achieved, minimal disease activity can be an acceptable goal. The combination of several immunosuppressive and biological drugs has been an effective therapeutic strategy in patients with rheumatoid arthritis [1], [2] and it would be worth to explore this strategy in SLE patients.

While corticosteroids remain the cornerstone drugs to control disease activity in SLE, other immunosuppressive agents are also used to treat several manifestations and, in many cases, they are prescribed for their steroid-sparing effect [3], [4], [5]. Rituximab (RTX), a chimeric monoclonal antibody against CD20 B cell receptor, has been approved by the Food and Drug Administration (FDA) for non-indolent lymphoma and also for rheumatoid arthritis who failed an anti-tumor necrosis factor (TNF) therapy. It has been enthusiastically used in SLE with positive clinical results in many case series [6], [7], [8], [9], [10]. However, two randomized clinical trials have been published recently that could not confirm those previous findings [11], [12], but clinicians are reluctant to accept these results and several explanations have been postulated [13], [14], [15].

In Latin America, the medical attention directed to systemic autoimmune diseases, such as SLE, competes with a budget designed to fight poverty, lack of education, sanitation, etc. In this context, the access to treatments recommended internationally are expensive and limited; therefore, research of methods that make these treatments cheaper is of paramount importance to improve the quality of life of our patients. We think that by using smaller doses than those previously recommended, but in combination with other drugs, could help to improve our patients' health. We have been using RTX as part of a combination therapy for SLE since 2003. The objective of this study was to describe the 24-month clinical outcome of our patients with active SLE who received low doses of RTX, followed by hydroxychloroquine (HCQ), prednisone and low doses of mycophenolate mofetil (MMF).

Section snippets

Patients

Forty-six patients, who fulfilled the American College of Rheumatology (ACR) classification criteria for SLE and had active disease, were invited to participate in this study. They received complete clinical information regarding therapeutic procedures and possible side effects. All of them accepted to participate following ethical guidelines. All the patients were seen and followed at the Unidad de Enfermedades Reumáticas y Autoinmunes (UNERA) in Cuenca and Guayaquil, Ecuador.

Corticosteroids

All patients

Effects on disease activity

Disease activity decreased over time with treatment (Table 1). At baseline, 19 (41.3%) patients had very severe, 16 (34.8%) severe, 9 (19.6%) moderate, and only 2 (4.3%) mild disease activity. No patient was on remission at baseline. Improvement on disease activity was detected at 3 months, since 9 (19.6%) patients reached disease remission after this period of time and remission increased to 16 (34.8%) patients at 6 months, 19 (41.3%) at 1 year, and 23 (50%) at 2 years of follow-up. The number of

Discussion

Therapy of SLE has different goals: (i) induction of response: aimed at rapidly controlling disease activity for prolonged periods; (ii) maintenance therapy: aimed at continuing remission and preventing flares; (iii) treatment of comorbidities: aimed at reducing the side effects of drugs employed to control activity and at controlling other associated conditions (i.e., hypertension, diabetes…) and minimizing damage. These aspects make the treatment of SLE complex and dependent on the use of

Take-home messages

  • In Latin America, the medical attention directed to systemic autoimmune diseases competes with a budget designed to fight poverty, lack of education, etc. Therefore, research of methods that make these treatments cheaper is of paramount importance.

  • Low doses of rituximab (RTX), followed by hydroxychloroquine (HCQ), prednisone and low doses of mycophenolate mofetil (MMF) is a combination regimen that was administered to 46 patients with active systemic lupus erythematosus in Ecuador.

  • Disease

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