Response of elderly patients with rheumatoid arthritis to methotrexate or TNF inhibitors compared with younger patients

Objective. To compare the efficacy of MTX and MTXþTNF inhibitors (TNFis) in elderly patients with RA with that in patients of younger age. Methods. Data from two large, randomized, controlled, double-blind trials in patients with early RA using adalimumab or infliximabþMTX or MTX alone were obtained and pooled. Composite disease activity indices were calculated at baseline and 1 year of treatment, and compared in groups of patients classified by quartiles of age with the highest age group comprising 61-82 years using analysis of variance or Kruskal- Wallis test. Results. Across all age quartiles, improvement on MTX was similar with respect to changes of composite disease activity indices, assess- ment of physical function and X-ray progression. Likewise, TNFiþMTX had similar effects across all age groups, but the effects of the combination were more profound than those of MTX monotherapy. Also in 10% of the patients with the highest age, primarily septuagenarians, improvement was seen to a similar degree as in the younger ones. Conclusions. Responsiveness of elderly patients with RA to MTX or TNFiþMTX is similar to that observed in patients of younger age. RA is the most common chronic inflammatory joint disease in adults, affecting 0.5-1% of the population. The incidence of RA increases with age, peaking between the fourth and sixth decade (1). Secular trends in time suggest that the mean age at diagnosis increases, as observed in a Finnish cohort, where the age of onset changed from a mean of 50 to almost 60 years during just one decade and the incidence rates declined in the younger age groups (2). These observations, in line with the increasing life expectancy in the industrialized world, suggest that the number of elderly patients requiring DMARD therapy will increase. The most important long-term consequence of RA is physical disability, which, however, is difficult to interpret. Disability has a component related to disease activity, which is reversible, and a component related to joint damage, which is irreversible (3). In elderly RA patients, the reasons of physical disability are even more complex, since the decline of physical function related to ageing must be considered (4). It has been suggested that RA in the elderly is a phenotypic variant and has an intrinsically different course compared with RA in younger individuals (5). This concept is further supported by reports on differences in the genetics of RA in the elderly (6). In light of these findings, it is of particular importance to under- stand the efficacy of DMARDs in elderly patients with established RA, since only DMARD therapy can effectively interfere with active disease, joint damage, and is able to prevent disability. The effect of DMARDs in elderly patients with RA has not been a main research focus over the past years, although two recent reports have found good clinical effects of disease modification, including the use of TNF inhibitors (TNFis), in elderly individuals (7, 8). However, the vast majority of these patients had longstand- ing disease; and in one of the studies, physical function in elderly RA patients did not improve. In contrast to studies of NSAIDs (9- 11), no major clinical trials have been designed addressing this particular population. Moreover, a recent review concluded that 'data are insufficient to provide much confidence in the potential beneficial effects of DMARDs in the elderly' (11). Therefore, older patients with RA are still less likely to receive DMARD treatment than their younger counterparts, and increas- ing age has been found to be an important determinant of less intensive RA care (12-14). As a consequence of applying less effective therapies, functional impairment might progress more rapidly in the elderly compared with younger patients with RA, especially since physical function is already naturally reduced in the elderly (4). The rapid decline in function could be further aggravated by a higher disease activity at onset. Together with an ineffective DMARD therapy, this may result in more radio- graphic damage as it has been observed in elderly when compared with younger patients with early RA (15). Based on these data, RA in the elderly could be viewed as not only being more severe, but also being less responsive to DMARD therapy. In the present study, we focused on patients with early RA to obviate potential effects of long disease duration on outcomes. We performed a subanalysis of pooled clinical trial data, and assessed the effect of age on the responsiveness of disease activity, physical function and joint damage in patients with early RA treated with MTX, or a combination of MTX with TNFi therapy.