Rheumatology Advance Access originally published online on May 7, 2008
Rheumatology 2008 47(7):1097-1099; doi:10.1093/rheumatology/ken015a
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Use of rituximab for the treatment of rheumatoid arthritis: the Latin American context
1Sección Reumatología, Servicio de Clínica Médica, Hospital Italiano de Buenos Aires y Fundación Dr Pedro M. Catoggio para el Progreso de la Reumatología, Buenos Aires, Argentina, 2Unidad de Enfermedades Reumáticas y Autoinmunes, UNERA, Hospital Monte Sinai, Cuenca, Ecuador, 3Unidad de Investigación Dr Mario Alvizouri Muñoz, Hospital General Dr Miguel Silva, Morelia, México, 4Servicio de Reumatología, Hospital Provincial de Rosario, Rosario, Argentina, 5Departamento de Inmunología Clínica y Reumatología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile, 6Unidad de Reumatología, Hospital Universidad del Norte, Barranquilla, Colombia, 7Complejo Hospitalario Metropolitano Dr Arnulfo Arias Madrid, Caja de Seguro Social de Panamá and Sociedad Panameña de Reumatología, Ciudad de Panamá, Panamá, 8Departamento de Reumatología, Hospital de Especialidades Bernardo Sepúlveda, Centro Médico Nacional Siglo XXI, IMSS, México DF, México, 9Servicio de Reumatología, Hospital Nacional Edgardo Rebagliati Martins, Red Asistencial Rebagliati (RAR), ESSALUD, Lima, Perú, 10Hospital México, Caja Costarricense del Seguro Social, San José, Costa Rica, 11Unidad de Reumatología, Hospital Central de San Cristóbal, Tachira, Venezuela, 12Servicio Nacional de Reumatología, Hospital Clínico Quirúrgico Diez de Octubre, Ciudad Habana, Cuba, 13Centro Médico Nacional 20 de Noviembre ISSSTE, México DF, México, 14Rheumatology Unit, São Lucas Hospital, PUCRS, Porto Alegre, 15Serviço de Reumatología, Hospital Heliópolis, São Paulo, 16Hospital Universitário de Brasília, Universidade de Brasília, Brasília, Brazil, 17Instituto Nacional de Rehabilitación, México DF, México and 18Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama, NY, USA
Correspondence to: C. Galarza-Maldonado, Hospital Monte Sinai, Unidad de Enfermedades Reumáticas y Autoinmunes, Miguel Cordero 6111 y Solano, Cuenca, Ecuador. E-mail: claudiogalarza{at}hotmail.com
KEY WORDS: Rheumatoid arthritis, Treatment guidelines, Biologic therapy, Anti-CD20 antibody, Rituximab, Latin America
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 Top Executive summary Guidelines for the use...AcknowledgementsReferences |
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Scope and purpose of the guidelines
GLADAR (Grupo Latino Americano de Estudio de Artritis Reumatoide) is a large group of Latin American (LA) rheumatologists experienced in the diagnosis and treatment of RA. In 2006, PANLAR and GLADAR published the first LA position paper on the pharmacological treatment of RA [1]. Since then, new therapies have emerged to help achieve the ultimate goal to preserve the patient's ability to function independently with an optimal quality of life.
The current guidelines provide evidence-based advice on the use of rituximab for physicians and rheumatologists treating RA in LA. A recent consensus publication has emanated from a group of European investigators [2]; however, as opposed to their work, our consensus document deals with the particulars of the use of rituximab in LA and it represents the work of GLADAR having been endorsed by all GLADAR centres.
This is a short summary of the whole guideline. The full guideline is available on the journal website.
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Guidelines for the use of rituximab in RA in LA |
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GLADAR agreed on 21 evidence-based recommendations (from A to D) [3], and an algorithm on the use of rituximab in RA patients (Fig. 1).
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Indications for rituximab
- (1) Rituximab may be used in patients with active [disease activity score (DAS) 28
3.2] RF-positive RA, who have had an incomplete response or intolerance to an adequate course with TNF inhibitors [4] as previously defined (A) [1].
- (2) Rituximab may also be used in patients with an inadequate response or intolerance to more than one conventional DMARD, who cannot receive TNF inhibitors (A) [5, 6].
- (3) There is no strong evidence to recommend rituximab to RF-negative RA patients [4, 6]; GLADAR, however, recommends that RF-negative patients be considered for treatment if they fulfil treatment failure criteria (B).
- (2) Rituximab may also be used in patients with an inadequate response or intolerance to more than one conventional DMARD, who cannot receive TNF inhibitors (A) [5, 6].
Who should administer rituximab?
- (4) A rheumatologist with experience in the diagnosis, evaluation and treatment of patients with RA should be the one managing this treatment. Treatment should be administered in an experienced infusion unit, with immediately available emergency care (D).
How should patients be screened before initiating rituximab?
- (5) A complete physical examination and detailed history searching especially for comorbid conditions and recurrent infections should be performed (D).
- (6) A chest radiograph is not mandatory but it is advisable (D).
- (7) Routine laboratory testing including CBC with differential should be included in the initial screening (D).
- (8) Baseline as well as prior to each infusion immunoglobulin levels (IgA, G, M) should be determined; if decreased levels are observed, it is advisable to infuse patients with immunoglobulins before initiating rituximab (D).
- (9) Hepatitis B, C and HIV serologies are recommended prior to treatment initiation. Patients with hepatitis B should not be treated with rituximab (D). Patients with hepatitis C could be treated with rituximab (D); however, before this is done, viral load needs to be assessed and proper anti-viral treatment should be given (D).
- (10) Vaccines with inactivated pathogens (hepatitis B, pneumococcus, influenza) should be administered at least 4 weeks prior to the administration of rituximab (D).
- (6) A chest radiograph is not mandatory but it is advisable (D).
How patients should be treated?
- (11) Patients who have already received anti-TNF therapy should receive a starting dose of 1000 mg per infusion on days 1 and 15 (A) [4].
- (12) GLADAR recommends that a dose of 2 x 1000 mg should be considered initially in most cases (Fig. 1; left side of the algorithm) (A), but 2 x 500 mg could be considered particularly in patients with prior inadequate response to traditional DMARDs (Fig. 1; right side of the algorithm) who have not received anti-TNF therapy (A) [6].
- (13) Rituximab should be administered in conjunction with methotrexate at adequate doses (A).
- (14) The decision to use other DMARDs or rituximab monotherapy for those patients who cannot tolerate methotrexate is left to the treating rheumatologist. Concomitant treatment with cyclophosphamide is not recommended (D).
- (15) The use of i.v. methylprednisolone (100 mg) prior to each rituximab infusion is recommended to reduce the frequency and severity of infusion reactions (A).
- (16) Repeated treatment should be considered in those patients who relapse (DAS 28
3.2) after initial response but only after 6 months have elapsed (C). Those patients with a good clinical response as per the defined criteria do not need to receive repeated treatment until they relapse (C) [7].
- (12) GLADAR recommends that a dose of 2 x 1000 mg should be considered initially in most cases (Fig. 1; left side of the algorithm) (A), but 2 x 500 mg could be considered particularly in patients with prior inadequate response to traditional DMARDs (Fig. 1; right side of the algorithm) who have not received anti-TNF therapy (A) [6].
How should patients be evaluated?
- (17) Patients should be assessed before treatment initiation and at least every 3 months thereafter. Although any composite activity index can be used, GLADAR strongly recommends the use of the DAS 28 because of its simplicity, friendliness and feasibility in daily clinical practice (D). A patient should be considered a responder if she/he achieves a DAS 28 score <3.2 at week 24. For patients who do not experience clinical improvement by week 12, GLADAR recommends optimizing the doses of concomitant therapies (e.g. increasing methotrexate or prednisolone doses, or administering intra-articular glucocorticoid injections) (D).
- (18) Measurement of human antichimeric antibodies (HACAs) antibodies is not required as part of the follow-up of patients treated with rituximab (A).
- (18) Measurement of human antichimeric antibodies (HACAs) antibodies is not required as part of the follow-up of patients treated with rituximab (A).
Contraindications
- (19) Rituximab should not be administered to children, pregnant women and during lactation, to patients allergic or hypersensitive to rituximab or any other chimerical and/or humanized antibodies (D).
- (20) Rituximab is contraindicated in the presence of active and recurrent infections and severe heart failure (New York Heart Association Class IV) (A).
- (20) Rituximab is contraindicated in the presence of active and recurrent infections and severe heart failure (New York Heart Association Class IV) (A).
Switching anti-TNF or giving rituximab
- (21) As there are no head-to-head studies comparing the efficacy and tolerance of the diverse biologic treatments available, whether to switch to another TNF inhibitor or start a new biologic agent is a decision best left to the experience of the treating rheumatologist and to the patient's preference (D) [8, 9].
These recommendations and guidelines are intended to help physicians and rheumatologists on the use of rituximab, but the ultimate decision of what is best for the individual patient should rest on the treating physician in close communication with the patient.
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Funding:The conceptualization of this consensus paper was made possible by an unrestricted grant from Roche.
Disclosure statement: E.R.S. has received grants from Abbott and support to attend ACR from Wyeth. M.H.C. has conducted clinical trials with rituximab as a principal investigator. L.M.H.M. has been a co-investigator in rituximab clinical trials for Roche and has received financial support for Medical Congress from Roche. C.G.-M. has been a principle investigator in biologic products clinical trials for Roche and Abbott. He has also received honoraria as an Advisory Board member for Wyeth. All other authors have declared no conflicts of interest.
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References |
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- Cardiel MH. First Latin American position paper on the pharmacological treatment of rheumatoid arthritis. Rheumatology (2006) 45(Suppl 2):ii7–22.
[Abstract/Free Full Text] - Smolen JS, Keystone EC, Emery P, et al. Consensus statement on the use of rituximab in patients with rheumatoid arthritis. Ann Rheum Dis (2007) 66:143–50.
[Abstract/Free Full Text] - Shekelle PG, Woolf SH, Eccles M, Grimshaw J. Clinical guidelines: developing guidelines. Br Med J (1999) 318:593–6.
[Free Full Text] - Cohen SB, Emery P, Greenwald MW, et al. Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum (2006) 54:2793–806.[CrossRef][ISI][Medline]
- Edwards JC, Szczepanski L, Szechinski J, et al. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med (2004) 350:2572–81.
[Abstract/Free Full Text] - Emery P, Fleischmann R, Filipowicz-Sosnowska A, et al. The efficacy and safety of rituximab in patients with active rheumatoid arthritis despite methotrexate treatment: results of a phase IIB randomized, double-blind, placebo-controlled, dose-ranging trial. Arthritis Rheum (2006) 54:1390–400.[CrossRef][ISI][Medline]
- Strand V, Balbir-Gurman A, Pavelka K, et al. Sustained benefit in rheumatoid arthritis following one course of rituximab: improvements in physical function over 2 years. Rheumatology (2006) 45:1505–13.
[Abstract/Free Full Text] - Bombardieri S, Ruiz AA, Fardellone P, et al. Effectiveness of adalimumab for rheumatoid arthritis in patients with a history of TNF-antagonist therapy in clinical practice. Rheumatology (2007) 46:1191–9.
[Abstract/Free Full Text] - Finckh A, Ciurea A, Brulhart L, et al. B cell depletion may be more effective than switching to an alternative anti-tumor necrosis factor agent in rheumatoid arthritis patients with inadequate response to anti-tumor necrosis factor agents. Arthritis Rheum (2007) 56:1417–23.[CrossRef][Medline]
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