DMARDs in Treatment of Rheumatoid Arthritis
Therapy of rheumatoid arthritis (RA) focuses on the retardation and, ideally, halting of the natural course of the disease using disease-modifying anti-rheumatic drugs (DMARDs) . However, insufficient efficacy of DMARDs and a significant degree of toxicity lead to relatively low retention rates for these drugs . As a consequence, RA patients are likely to receive several compounds consecutively during the course of their chronic disease. We also describe the pattern of initial DMARDs employed in new patients over the past two decades. We also explored the preferred DMARDs when preceding ones had failed. Finally, our data may provide a basis for expectations and future measures of success of traditional as well as the new, recently approved DMARDs.
The influence of selection bias on the identified patients is considered very low, as data were extracted from the files in 1999 but files of all RA patients, including those with long-standing RA, who were seen in the out-patient clinics at least once after 1993, are kept in the archives. Therefore, charts of patients who were lost to follow-up or had died since 1993 were also available, and the only charts that were not available for analysis were those for patients who had no visit after 1993. To determine the potential presence and degree of bias, we analysed disease duration for therapies and reasons for treatment discontinuation before and after 1993, and found no significant difference.
Five hundred and ninety-three patients were identified in the two clinics and were followed throughout their DMARD therapies until the last evaluation in 1999. The ratio of women to men was 4:1. Testing for rheumatoid factor at the time of first presentation at the clinics was positive in 379 patients (63.9%) and negative in 214 (36.1%). The patients’ mean age (±S.D.) at the time of study was 59.1±13.6 yr and the mean disease duration was 12.1±9.3 yr. These patients received a total of 1319 courses of DMARDs. The number of DMARD courses prescribed to an individual RA patient ranged from 1 to 10 (median 2). A total of 2376 patient-years (p.y.) of DMARD therapy were analysed and involved the following therapies (numbers of p.y. are rounded): auranofin (OG; n=68, 131 p.y.), azathioprine (AZP; n=25, 56 p.y.), antimalarials (AM; n=285, 536 p.y.), cyclosporin A (CyA; n=31, 27 p.y.), D-penicillamine (DPA; n=65, 164 p.y.), methotrexate (MTX; n=389, 751 p.y.), parenteral gold compounds (PG; n=109, 218 p.y.), sulphasalazine (SSZ; n=267, 428 p.y.) and combination therapies (Comb.; n=80, 67 p.y.).
The data reveal that CQ, SSZ and MTX were used to a similar extent in the early phase of therapy. Certain characteristics of the patients or their disease must have led to the choice of either one of these drugs, as the efficacy/toxicity trade-offs are similar for these drugs. In fact, the acute-phase response at treatment initiation was significantly higher in patients on MTX than in those who were beginning CQ or SSZ. MTX was the most commonly employed DMARD therapy for RA and was used increasingly as first therapy in newly diagnosed RA. Patients with high disease activity were given MTX therapy more often than other DMARDs, while those with low activity were more likely to receive SSZ or AM, and MTX on failure of these drugs. First DMARDs in new patients were retained longer than subsequent DMARDs, apparently because they are more effective.
