The introduction of biologic agents has substantially increased the options for treatment of RA and significantly improved the outcome. To achieve a status of low disease activity or even remission has become a realistic goal of treatment. Interestingly, this is the case not only for patients treated with these new agents but also for patients treated with conventional DMARDs. This study was conducted to investigate the remission rates according to two different criteria and the achievement of two endpoints for functional outcome (functional remission and functional independence) in a cohort of patients treated with biologics in daily practice and to compare these results with a control group of patients who changed their conventional DMARD treatment because of inefficacy or intolerance.
Of the BIOL patients, 16% achieved a DAS28 <2.6 at 12 months and 13% achieved remission according to the modified ARA criteria. The figures in the control group were 15% and 10%, respectively. Adjusting for differences in the case mix, we found that biologics doubled the chance of remission in active RA patients treated in routine care.
Sustained remission over a longer period of time is difficult to achieve [8
]. Approximately half of our patients in remission at six months relapsed at 12 months, although they were under continuing rheumatologic care. This proportion is high, but it is in agreement with the findings of others [8
]. For this reason, the original ARA criterion is likely to be stronger than the DAS28 criterion, since it requires ongoing remission for at least two months and also a complete absence of symptoms in the feet, which are not included in the calculation of the DAS28. These differences are more important [22
] than the calculation of other cutoff values for the DAS28 remission as proposed by others [16
To evaluate differences in remission rates, the risk profile of the patients treated had to be taken into account. Disease activity at start of treatment [21
], disease severity, age, previous DMARD failures and comorbidities [26
] indicating disease severity (for example, corticoid induced osteoporosis) were found to influence the achievement of remission. The DAS28 at baseline was the strongest predictor of remission in our data, more important than single joint counts or ESR. The chance of remission decreased with an increasing DAS28. We found that in addition to the DAS28, markers of disease severity such as rheumatoid factor [21
], disability [21
] or osteoporosis were significantly associated with the outcome. Higher rates of remission were found in patients with up to two years of disease duration. As the number of patients with early RA was too small in our data, this difference did not reach statistical significance. However, the small number of patients with early disease likely explains the differences between the remission rates found in this study and the distinctly higher rates found by others in recent onset RA [27
]. Our remission rates at 12 months are comparable to those found in routine care (16% in [29
] and 14% in [30
]) or under treatment with etanercept alone or MTX alone (18% and 17%, respectively) [20
]. Van der Heijde and colleagues [20
] reported higher DAS28 remission rates (38%) in patients receiving a combination therapy of etanercept and MTX. Of note, patients enrolled into the TEMPO trial (Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes) [20
] had a higher a priori
chance of remission because of a lower number of previous DMARD failures (2.3 on average; no failure of a MTX therapy) and a lower percentage of positive rheumatoid factor (76%) than our patients [31
]. We found higher treatment continuation rates in patients treated with anti-TNF agents in combination with MTX compared to those receiving anti-TNF drugs alone [10
], but we did not find any significant differences in the remission rates between both subgroups. More detailed analyses may be needed to determine the reasons for this finding; these analyses were beyond the scope of this paper.
Grigor and colleagues [29
] showed that intensive care with a tight control of disease activity can lead to very high DAS remission rates (65%). The fact that in comparison to our patients, their patients had better preconditions regarding predictors of remission, such as disease duration or previous DMARD combination therapy, still does not provide a feasible explanation for the large difference in the remission rates. Therefore, further evaluation of this treatment strategy is needed.
It has been shown in randomized controlled trials that biologics can effectively improve function [2
]; however, most of these trials excluded severely disabled patients [1
]. This is in contrast to daily rheumatologic care in which severely disabled patients are preferred candidates for biologic treatment. Our findings suggest that especially severely disabled patients benefit from treatment with biologics. In these patients, the chance to achieve physical independence was found to be approximately four times higher if treated with biologics compared to conventional DMARDs. Furthermore, sub-sample patients who were below the threshold of physical independence at baseline were significantly more likely to achieve functional remission when a treatment with biologics was chosen.