Combination therapy in early rheumatoid arthritis: a randomised, controlled, double blind 52 week clinical trial of sulphasalazine and methotrexate compared with the single components
- Maxime Dougados,
- Bernard Combe,
- Alain Cantagrel,
- Philippe Goupille,
- Patrick Olive,
- Manfred Schattenkirchner,
- S Meusser,
- L Paimela,
- Rolf Rau,
- Henning Zeidler,
- Marjatta Leirisalo-Repo,
- Kristiina Peldan
- Dr M Dougados, Institut de Rhumatologie, Hardy B, Hôpital Cochin, 27 rue du Fg Saint-Jacques, 75014 Paris, France.
- Accepted 4 November 1998
Abstract
OBJECTIVES To investigate the potential clinical benefit of a combination therapy.
METHODS 205 patients fulfilling the ACR criteria for rheumatoid arthritis (RA), not treated with disease modifying anti-rheumatoid drugs previously, with an early (≤1 year duration), active (Disease Activity Score (DAS) > 3.0), rheumatoid factor and/or HLA DR 1/4 positive disease were randomised between sulphasalazine (SASP) 2000 (maximum 3000) mg daily (n = 68), or methotrexate (MTX) 7.5 (maximum 15) mg weekly (n = 69) or the combination (SASP + MTX) of both (n = 68).
RESULTS The mean changes in the DAS during the one year follow up of the study was −1.15, −0.87, −1.26 in the SASP, MTX, and SASP + MTX group respectively (p = 0.019). However, there was no statistically significant difference in terms of either EULAR good responders 34%, 38%, 38% or ACR criteria responders 59%, 59%, 65% in the SASP, MTX, and SASP + MTX group respectively. Radiological progression evaluated by the modified Sharp score was very modest in the three groups: mean changes in erosion score: +2.4, +2.4, +1.9, in narrowing score: +2.3, +2.1, +1.6 and in total damage score: +4.6, +4.5, +3.5, in the SASP, MTX, and SASP + MTX groups respectively. Adverse events occurred more frequently in the SASP + MTX group 91% versus 75% in the SASP and MTX group (p = 0.025). Nausea was the most frequent side effect: 32%, 23%, 49% in the SASP, MTX, and SASP + MTX groups respectively (p = 0.007).
CONCLUSION This study suggests that an early initiation therapy of disease modifying drug seems to be of benefit. However, this study was unable to demonstrate a clinically relevant superiority of the combination therapy although several outcomes were in favour of this observation. The tolerability of the three treatment modalities seems acceptable.
Footnotes
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Details of authors and institutions given at end of article.
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Maxime Dougados, Institut de Rhumatologie, Hôpital Cochin, Paris, France; Bernard Combe, Patrick Olive, Fédération de Rhumatologie, Hôpital Lapeyronnie, Montpellier, France; Alain Cantagrel, Service de Rhumatologie, CHU Rangueil, Toulouse, France; Philippe Goupille, Service de Rhumatologie, CHU Trousseau, Tours, France; Manfred Schattenkirchner, Rheuma-Einheit, Ludwig-Maximilian-Universitat, Munich, Germany; S Meusser, Medizinische Klinik III, Universitat Erlangen-Nurnberg, Erlangen, Germany; L Paimela, Kivelan Sairaala, Helsinki, Finland; Rolf Rau, Rheumatology, Evangelisches Fachkrankenhaus, Ratingen, Germany; Henning Zeidler, Division of Rheumatology, Department of Internal Medicine and Dermatology, School of Medicine at Hannover, Hannover, Germany; Marjatta Leirisalo-Repo, Department of Medicine, Division of Rheumatology, University of Helsinki, Helsinki, Finland; Kristiina Peldan, Jorvi Hospital, Espoo, Finland.
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Funding: this study was supported in part by a grant from Pharmacia Upjohn.
