Drug survival, efficacy and toxicity of monotherapy with a fully human anti-tumour necrosis factor-[alpha] antibody compared with methotrexate in long-standing rheumatoid arthritis

• Published in: Rheumatology (Oxford, England) Vol. 41; no. 4; p. 430
• Main Authors: Barrera, P, van der Maas, A, van Ede, A E, B. A. L. M. Kiemeney, R. F. J. M. Laan, L. B. A. van de Putte, P. L. C. M. van Riel
• Format: Journal Article
• Language: English
• Published: Oxford Oxford Publishing Limited (England) 01.04.2002
• ISSN: 1462-0324; 1462-0332

Objectives. To compare the 48-week drug survival, efficacy and toxicity of monotherapy with a fully human anti-tumour necrosis factor-[alpha] (TNF-[alpha]) monoclonal antibody (moAb) and methotrexate (MTX) in patients with active long-standing rheumatoid arthritis (RA). Secondary aims were to identify potential predictors for clinical response. Methods. Patients with RA, enrolled in phase I trials with a human anti-TNF-[alpha] moAb and followed for at least 48 weeks at our centre, were compared with patients receiving MTX monotherapy without folate supplementation. The first 6 weeks of anti-TNF therapy were placebo-controlled and followed by an open-label study. Patients treated with MTX participated in a 48-week, double-blind, phase III study of MTX alone vs MTX with folate supplementation, which was co-ordinated by our department. The studies with anti-TNF-[alpha] and MTX were performed in the same period and had very similar inclusion, exclusion, response and stop criteria. Results. Sixty-one patients treated with anti-TNF-[alpha] moAb were compared with 137 receiving MTX monotherapy. At baseline, patients in the anti-TNF-[alpha] group had a longer disease duration (median 108 vs 50 months, P=0.0001) and a more protracted history of second-line anti-rheumatic drugs than those treated with MTX (median 4 vs 1, P=0.0001). The 48-week dropout rate was lower among patients treated with anti-TNF (23 vs 45% in the MTX group, P<0.005). Proportional hazard analysis showed a significantly lower dropout risk among anti-TNF-treated patients [relative risk (95% confidence interval): 0.28 (0.12-0.6) uncorrected and 0.17 (0.06-0.45) corrected for confounders). The 48-week area under the curve for the disease activity score (DAS) was smaller in the anti-TNF-[alpha] group than in the MTX group (P=0.005). The percentage of responders was higher in the anti-TNF-[alpha] group over the whole study period. The median percentage of visits in which a patient fulfilled the European League Against Rheumatism (EULAR) response criteria was 83% in the anti-TNF-[alpha] group vs 40% in the MTX group (P=0.0001). Clinical and demographic characteristics were, in general, poor predictors for response to therapy at week 48. The clinical response after the first anti-TNF-[alpha] dose tended to increase the chance of prolonged efficacy of this approach [relative risk (95% confidence interval): 2 (0.75-6.0)]. The previous number of second-line drugs was the only predictive variable for response to MTX to which it was inversely related [relative risk (95% confidence interval): -0.71 (-0.57 to -0.88)]. Conclusions. In patients with active, long-standing RA, blocking TNF-[alpha] is more effective and better tolerated than MTX monotherapy. An early response increases the chance of a sustained effect of anti-TNF-[alpha]. In contrast to MTX, the response to anti-TNF-[alpha] is not affected by previous disease-modifying anti-rheumatic drug history.