The main finding of the present study is that targeting to remission with traditional DMARDs and tight clinical controls results in low radiologic progression in most RA patients. Still, patients treated initially with the FIN-RACo strategy during the first 2 years have less radiographic damage in small joints, even in long term than did those treated initially with DMARD monotherapy.
Less radiographic damage is found in RA patients at present than during previous decades [13
]. In our study, both treatment arms had excellent radiologic small-joint outcome compared with historic cohorts. In a previous Finnish cohort of 103 patients with early RA, beginning in the 1970 s, the radiologic progression was steepest during the first 8 years but continued throughout the follow-up of 20 years [1
]. In that cohort, the mean ± SD Larsen score at 3 years was 27 ± 21, and at 15 years, 78 ± 49. Thus, after 3 years of RA, the historic patients had comparable amounts of radiographic damage to the patients of the present study at 11 years. In a Swedish cohort starting in 1985, 181 patients with conservatively treated early RA had, at 10 years, a median Larsen score of 54 (IQR, 28 to 80) [2
], thus double the Larsen score of our patients at 11 years. These findings are in accordance with those of Finckh et al.
], who found that the radiographic prognosis of RA has improved during the past decades parallel to more active treatments.
Even though most patients had excellent radiographic results at 11 years, the patients treated with the FIN-RACo strategy had significantly lower increases in the median Larsen score from baseline to 11 years than did the SINGLE patients, and besides the presence of rheumatoid factor, only the initial SINGLE treatment predicted the radiographic progression at 11 years in the ordered logistic regression analysis. The main difference between the groups had developed during the first 2 years; after that, both groups progressed similarly. For unknown reasons, the dropout patients in the FIN-RACo group had a higher Larsen score at baseline than did those cases who completed the study. Thus, in the completers of the FIN-RACo group, a trend toward a lower Larsen score at baseline was seen compared with the SINGLE group completers. At worst, this fact may bias the study. However, in the statistical analysis adjusted with baseline Larsen score, a highly significant difference in radiologic progression was found between the groups. Therefore, we find it justified to conclude that the observed difference between the groups represents rather the results of a more-effective initial DMARD treatment strategy than a biologic bias.
For evaluating the radiographic damage, we used the Larsen score, which has been found to be less sensitive to change than the Sharp/van der Heijde method [14
]. Conversely, the Larsen method tends to be more specific than the Sharp/van der Heijde method [14
], and when the follow up is as long as 11 years, we prefer specificity over sensitivity; it is more important to distinguish clinically relevant from unspecific changes than to find subtle joint-space narrowing. Also, the intraobserver reliability in Larsen score is somewhat better than that of the Sharp/van der Heijde method [15
], and because we have had the same experienced radiologist scoring the radiographs with the Larsen method throughout the follow-up, we find this method logical. To our knowledge, no other methods exist for evaluating the radiographic progression in large joints besides the Larsen method.
Only 13% of the FIN-RACo and 28% of the SINGLE patients had some radiographic damage in large joints. Few long-term studies of early RA assess large-joint damage, and none of them have a definite treatment protocol. One study, published in 1997, found radiographic damage in large joints in 50% of the patients after 6 years of RA [17
]. In a Dutch study, 54% of patients had at least one eroded large joint after 12 years of RA [18
]. In the present study, the infrequent destruction of large joints was also reflected in the small number of total joint replacements in both of our treatment groups compared with earlier cohorts [19
], even though the follow-up of 11 years is too short to evaluate the final incidence of total joint replacements.
Probably the most important precondition to our excellent results in most patients was the active treatment policy aiming at remission at all time points. Even though recent reports showed that radiologic progression may occur even while the patient appears to be in remission [20
], most damage still emerges in clinically inflamed joints [21
]. Our results emphasize the importance of early remission for the long-term outcome of the patients. In the present study, the patients who had been in strict remission at 1 year had significantly less radiologic progression throughout the follow-up than did the patients who had not reached remission at 1 year. Remissions were reached more often by the FIN-RACo arm patients than by the SINGLE patients at 2 years [3
], as well as at 11 years [11
], but patients in both treatment arms had mainly low disease activity and well-preserved function throughout the follow-up [11
]. This clinical profile fits the radiologic profile of our study groups well; compared with less aggressively treated patients, both groups were doing well, but the FIN-RACo patients even better.
We earlier reported that during the liberal treatment phase between years 2 and 11, the use of DMARDs differed between groups, with combination treatments used more often in the original FIN-RACo group [11
]. This difference had, however, no impact on the clinical outcome at 11 years. In the FIN-RACo group, the patients who had low disease activity at 11 years had received significantly shorter periods of combination DMARDs between 2 and 11 years than had the patients who had high disease activity at 11 years [11
]. Similarly, in the present study, the patients with the least radiologic progression after year 2 had received the shortest periods of combination DMARD strategy after 2 years. These results are in agreement with the fact that in longitudinal observational studies, the cases treated most intensively are the most likely ones to have the most severe disease [22
]. And yet, aggressive treatments in established disease do not seem to gain as much effect as they do in early disease. This emphasizes the importance of early, effective treatment and tight control of therapeutic response. Late strengthening of DMARD treatment is not able to reverse the damage already arisen. Nevertheless, it is probable that radiologic progression would have been even steeper had the treatments during the liberal phase been less aggressive.
Glucocorticoids were a part of the FIN-RACo strategy and were allowed in the SINGLE strategy to reach remission. Because glucocorticoids have been shown to retard radiologic progression [5
], it could be hypothesized that their use would explain the difference in Larsen score between the groups. However, the patients treated with the FIN-RACo strategy needed fewer intraarticular glucocorticoid injections and had a smaller cumulative dose of glucocorticoids during the first 2 years than did the SINGLE strategy group [3
]. Thus, the better radiologic outcome in the FIN-RACo arm does not seem to depend on the use of glucocorticoids, but rather on the more effective and rapidly working DMARDs during the critical "window of opportunity." Whether the difference between the groups would have been smaller, had the first DMARD in the SINGLE strategy been methotrexate, cannot be answered by this study. However, the SINGLE strategy was not tied to sulfasalazine but to a strategy of using one DMARD at a time, and, during the first 2 years, 52% of patients in the SINGLE group were switched to methotrexate [3