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  • Comparative effectiveness of switching to alternative tumour necrosis factor (TNF) antagonists versus switching to rituximab in patients with rheumatoid arthritis who failed previous TNF antagonists: the MIRAR Study

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Clinical and epidemiological research
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Comparative effectiveness of switching to alternative tumour necrosis factor (TNF) antagonists versus switching to rituximab in patients with rheumatoid arthritis who failed previous TNF antagonists: the MIRAR Study
  1. Juan J Gomez-Reino1,
  2. Jose Ramon Maneiro1,
  3. Jorge Ruiz2,
  4. Rosa Roselló3,
  5. Raimon Sanmarti4,
  6. Ana Belen Romero5 on behalf of the MIRAR Study Group
  1. 1Department of Rheumatology, Hospital Clínico Universitario, Universidad de Santiago de Compostela, Santiago, Spain
  2. 2MIXESTAT, SL, Barcelona, Spain
  3. 3Department of Rheumatology, Hospital San Jorge, Huesca, Spain
  4. 4Department of Rheumatology, Hospital Clínic i Provincial, Barcelona, Spain
  5. 5Roche Laboratories, Madrid, Spain
  1. Correspondence to Dr Juan J Gomez-Reino, Department of Rheumatology Unit, Hospital Clinico Universitario, Santiago de Compostela, Santiago, Spain; juan.jesus.gomez-reino.carnota{at}sergas.es

Abstract

Objective To compare the effectiveness of switching to rituximab (RTX) with switching to alternative tumour necrosis factor (TNF) antagonists in patients with rheumatoid arthritis (RA) failing on TNF antagonists.

Methods A multicentre prospective 3-year observational study was performed in patients with RA treated with RTX or an alternative TNF antagonist. The baseline 28-joint disease activity score (DAS28) and Health Assessment Questionnaire (HAQ) score were compared with 6, 9 and 12 month values, adjusting for propensity score quintiles. Propensity scores were estimated for each patient using logistic regression with treatment as the dependent variable and baseline prior number of TNFs >1, years from diagnosis >5, extra-articular manifestations, previous toxicity, use of ≥2 disease-modifying antirheumatic drugs, age and sex as independent variables.

Results 1124 patients were treated with either RTX (n=591, 52.6%) or alternative TNF antagonists (n=533, 47.4%). RTX-treated patients had longer disease duration (p=0.0001), larger numbers of previous TNF antagonists (p<0.0001) and tender and swollen joints (p<0.0001). There was no significant difference in the reduction in DAS28 at 6, 9 and 12 months between RTX-treated patients and those treated with TNF antagonists. However, the reduction in DAS28 was significantly different between RTX-treated patients and adalimumab/infliximab-treated patients (p=0.001 and p=0.05, respectively). There was a marginally significant difference at any time period in the proportion of patients achieving an improvement in the HAQ score of >0.22 (p=0.06).

Conclusions Optimal treatment for patients with RA failing on treatment with TNF antagonists may include RTX. This study suggests that the improvement in DAS28 is larger in patients treated with RTX than in those treated with monoclonal anti-TNF agents.

https://doi.org/10.1136/annrheumdis-2012-201324

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    Footnotes

    • ▸ An additional figure is published online only. To view this file please visit the journal online (http://dx.doi.org/10.1136/annrheumdis-2012-201324)

    • MIRAR Study Group Alicia García, Juan Povedano, Paula Cejas (Hospital Virgen del Rocío, Sevilla); Federico Navarro, José Alejandro Ariza Ariza, Silvia Ricca (Hospital Virgen Macarena, Sevilla); Juan Sánchez Bursón (Hospital Valme, Sevilla, Spain); Wenceslao Herranz Mediano (Hospital Ntra Sra de la Merced de Osuna, Sevilla); Manuel A. Guzmán Ubeda, Purificación Salas Blanca (Hospital Virgen de las Nieves, Granada); Enrique Raya, Pilar Morales Garrido, Amalia Rueda (Hospital San Cecilio, Granada); Manuel Romero (Hospital General de Jaén, Jaén); Antonio Fernández, Ángeles Belmonte (Hospital Carlos Haya, Málaga); Rosa García (Hospital Virgen Victoria, Málaga); Adela Ruíz (Hospital Reina Sofía, Córdoba); José J. Pérez Venegas (Puerta del Mar Cádiz); José Salberii, Raúl Menor, Yolanda Grandal, Manuel Paez-Camin, Mª del Mar Ruiz (Hospital Jerez de la Frontera, Cádiz); Dolores Mendoza, Manuel Riesco, Celia Fernández (Hospital Juan Ramón Jiménez, Huelva); Concepción Delgado (Hospital Clínico Zaragoza, Zaragoza); Rosa Roselló (Hospital San Jorge, Huesca); Dr. Pina, Dolores Fabregas (Hospital de Barbastro, Huesca); Mª Loreto Horcada (Hospital Obispo Polanco, Teruel); Juan Carlos Torre Alonso (H. Naranco, Asturias); Francisco Javier Ballina García, Mercedes Algeri López, Rubén Queiro Silva, José Luis Riertra Noriega (Hospital Central de Asturias, Asturias); Luis Arboleya (Hospital San Agustín, Asturias); Tomás Tinturé (Hospital Cabueñes, Asturias); Luis Espadaler Poch, Jordi Fiter Areste (Hospital Son Dureta, Mallorca); Inmaculada Ros Vilamajó, Antonio Juan Mai (Hospital Son Llatzer, Mallorca); Teresa Font (Hospital Comarcal d'Inca, Mallorca); Miguel Pericas Alemany (Hospital de Manacor, Mallorca); Ana Urruticoechea Arana (Hospital Can Misses, Ibiza); Sagrario Bustabad, Ivan Ferraz (HCU Canarias, Tenerife); Alberto Cantabrana (Hospital Candelaria, Tenerife); Daniel Batista, J Angel Hdez (Hospital Insular, Las Palmas); Juan Carlos Quevedo, Íñigo Rúa- Figueroa (Hospital Dr. Negrín, Las Palmas); Jaime Calvo, Elena Arrecoechea, Teresa Jimeno (Hospital Sierrallana Torrelavega, Cantabria); Raimon Sanmarti, M. Victoria Hernández (Hospital Clinic, Barcelona); Carme Moragues, Ingrid Möller (Clínica Platón, Barcelona); Nishishinya Mª Batina, Díaz Torné, Vicente Torrente Segarra, Asunción Acosta (Hospital Sant Pau, Barcelona); Mª Bonet (Hospital de Vilafranca, Barcelona); Eduardo Kanterewicz, José Rodriguez (Hospital de Vic, Barcelona);Ramón Figuls (Creu Roja Barcelona, Barcelona); Marta Larrosa Padró, Antonio Gómez (Hospital Parc Tauli de Sabadell, Barcelona); José Valverde García, Elena Sirvent, Delia Reina Sanz (Hospital Bellvitge); Jose Miguel Ruiz, Sergio Ros (Hospital Viladecans, Barcelona); Jordi del Blanco (Hospital de Calella, Barcelona); Joan Maymó, Mapi Lisbona, Carolina Pérez, Miriam Almirall, Núria Aizpunua Perez, Silvia Sánchez (Hospital del Mar, Barcelona); Alejandro Olivé, Elisa Garcia (Hospital German Trias i Pujol, Barcelona); Georgina Salvador, Elena Riera (Hospital Mutua Terrassa, Barcelona); Dra. Marsal (Hospital Vall d'Hebrón, Barcelona); Maria Isabel Rotés, Alba Erra, Estefania Moreno (Hospital Sant Rafael, Barcelona); Teresa Claveguera, Ramón Valls (Hospital Palamós, Girona); Miquel Sala, Marta Valls (Hospital Figueres, Girona); Lluis Roselló (Hospital Sta. María, Lleida); Sergi Ordoñez Palau (Hospital Arnau de Vilanova, Lleida); Silvia Paredes (Hospital St Joan Reus, Tarragona); Josep Pujol, Rosa Morlà (Hospital St Pau i Sta. Tecla, Tarragona); Ramon Fontova Garrofí, Mª José Poveda Elias (Hospital Joan XXIII, Tarragona); X. Arasa (Hospital Verge de la Cinta, Tarragona); Alfons Lorenzo Querol, Mª José Poveda Elias (Pius Hospital de Valls, Tarragona); Enrique Judez, Gloria Garcia (Complejo Hosp. Albacete, Albacete); Paula Virginia (Complejo Hosp. Ciudad Real); Julio Vázquez (Hospital Virgen de la Luz, Cuenca); Pilar Muñoz (Hospital Guadalajara, Guadalajara); Juana Sampedro Álvarez, Angel M García Aparicio, Azucena Hernández Sanz, Jose Rey Rey (Hospital de Toledo, Toledo); Montserrat Corteguera (Hospital Ntra. Sra. Sonsoles, Avila); Manuel Martín Martínez (Hospital de León, Leon); Lucia Pantoja (Hospital del Bierzo, Leon); Dr. Montilla (Hospital Virgen de la Vega, Salamanca); Purificación Ruiz (Hospital Insalud Soria, Soria); JM Martín Santos (Hospital Río Ortega, Valladolid); Jose Luis Alvarez Vega, Jose Maria Salazar (Hospital Infanta Cristina, Badajoz); Eugenio Chamizo, Juan Jose Aznar, Noemí Garrido (Hospital Mérida, Badajoz); Antonio Cardenal Escarcena, Antonia Ferreira Conejo (Hospital Don Benito, Badajoz); Raúl Veroz González (Hospital Llerena, Badajoz); José García Toron (Hospital San Pedro Alcántara, Cáceres); Miguel Ángel Abad, María Torresano Andrés (Hospital Virgen del Puerto, Cáceres); Mercedes Freire, Jenaro Graña (Hospital Juan Canalejo, A Coruña); Marina Rodriguez López, Mª Ángeles Hernández (Complejo Hospitalario Arquitecto Marcide- Novoa Santos, A Coruña); Jorge Blanco Rodríguez, Juan José Díaz Garel (Complejo Hospitalario Universitario de Santiago, A Coruña); Manuel Rodríguez Fernández, Luis Fernández Domínguez, Alfredo Willisch Domínguez (Hospital Cristal Piñor, Ourense); Juan Cruz Martinez (Hospital provincial de Pontevedra, Pontevedra); Rubén Ouviña, Iñigo Hernández (Hospital Mexoeiro, Pontevedra); Ceferino Barbazán (Hospital Xeral Cíes; Pontevedra); José Ángel Cabezas (Hospital San Millán y San Pedro, La Rioja); Julio Gracia Estevez (Hospital general de la Rioja, La Rioja); Dra. Mateo, Beatriz Joven, María Galindo, Luis Morillas, Pilar Fernández Dapica, Laura González Hombrados, Padrino Herrera, Javier García (Hospital 12 de Octubre, Madrid); María Alcalde, Esperanza Naredo, Paz Collado, Dr. Crespo (Hospital Severo Ochoa, Madrid); Luis Carreño, Dr. Gonzalez, Francisco Javier López, Marilyn Salvat, Indalecio Monteagudo (Hospital Gregorio Marañón); Esther Vicente Rabaneda, Esther Coledaro (Hospital Princesa, Madrid); Dra. Sánchez Atrio (Hospital Príncipe de Asturias, Madrid); Tatiana Cobo, Martina Steiner (Hospital La Paz, Madrid); Paloma de Abreu, Oscar Illera (Hospital Ramón y Cajal, Madrid); Ana Castilla Plaza (Hospital Carlos III, Madrid); Roberto Mígueles Sánchez, Mª Cruz Fdez Espartero, Virginia Villaverde García, Mercedes Morcillo Valle, Jacqueline Usón Jaefer (Hospital Móstoles, Madrid); Dr. Prada, Dr. Mulero (Hospital Puerta de Hierro, Madrid); Pedro Zarco (Fundación hospital de Alcorcón, Madrid); María Luisa González (Hospital Comarcal El Escorial, Madrid); Ángel Aragón (Hospital de Getafe, Madrid); Carlos Rodríguez Escalera (Hospital Comarcal de Melilla, Melilla); Francisco García Villalba, Manuel Moreno Ramos, Juan Moreno Morales (Hospital Santa María del Rosell, Murcia);Carmelo Tornero, Encarnación Saiz Cuenca (Hospital Morales Moseguer, Murcia); Carlos Marras, Nuria Lozano (Hospital Virgen de la Arrixaca, Murcia);Emilia Aznar (Hospital Reina Sofía, Navarra); Eduardo Loza Cortina, Concepción Fito, Natividad del Val, Rosario Ibañez, Ricardo Gutierrez (Hospital de Navarra, Navarra); Juan Carlos Vesga (Hospital de Txagorritxu Vitoria, Álava); Alberto Alonso Ruiz (Hospital de Cruces, Vizcaya); José Miguel Aramburu Albizuri, M. Luz García, Eva Galinder, Eduardo Ucar, Manuel Gorordo, Arantza Pacho, Iñaki Torre, Francisco García, Olaia Fernandez (Hospital de Basurto, Vizcaya); Flores Torre, Aintzane Ruiz Diez (Hospital de Galdákano, Vizcaya); Joaquín Belzunegui (Hospital de Donostia, Guipuzcoa); Paloma Vela (Hospital General Alicante, Alicante); Dra. Jovaní, Cristina Fernández (Hospital General de Elda, Alicante); Miguel Belmonte (Hospital General de Castellón, Castellón); José A. González, Francisco Navarro Blasco, Juan Tovar Beltran, José Raúl Noguera (Hospital General Elche, Alicante); Mauricio Minguez (Hospital Clínico San Juan, Alicante); Francisco Pérez (Hospital de Requena, Valencia); Pascual Muñoz (Hospital de Xativa, Valencia); Dra. Martínez (Hospital Alzira, Valencia); Dra. Alcañiz (Hospital Dr. Peset, Valencia); Antonio Gracia Pérez (Hospital Sagunto, Valencia); Juan Antonio Castellano, Antonio Pérez (Hospital Arnau de Vilanova, Valencia); Isabel González -Cruz (Hospital General de Valencia, Valencia); Hospital Marqués de Valdecilla, Cantabria; Hospital Miguel Servet, Zaragoza.

    • Funding The study was supported by Roche, Spain.

    • Competing interests JJG-R is on the Advisory Boards of BMS, Pfizer, Roche, Schering-Plough and UCB SA; has received lecture fees from, BMS, Roche, Schering-Plough and Wyeth; and has received research grants from Roche and Schering-Plough. All other authors have declared no conflicts of interest.

    • Patient consent Not obtained.

    • Ethics approval Ethics approval was obtained from the ethics committee of the Hospital Clinic i Universitary, Barcelona (Spain).

    • Provenance and peer review Not commissioned; externally peer reviewed.