Although there have been many RCTs regarding dose tapering strategies of bDMARDs in patients with RA, there is no general consensus regarding who is suitable for tapering and how to taper the dose . This discrepancy is mainly due to the fact that RCTs, contrary to daily clinical practice, include a selective group of patients and follow strict study protocols. Therefore, the efficacy and safety of tapering bDMARD dose in real-world practice may differ from those reported in RCTs. In this context, the results of this study provide important evidence for clinical decisions on tapering TCZ dose in daily practice. To fully consider the heterogeneity of tapering strategies in the real world, we performed a longitudinal analysis including all clinical variables, including the dose of TCZ and disease activity measured at all 1-year intervals for the study subjects.
Our results showed that CDAI remission was achieved in approximately 15% of the study population, and this did not increase over time. Although previous studies have demonstrated that achieving ‘remission’ can predict the best prognosis in patients with RA, many observational cohort studies have shown that patients do not often reach the optimal target, especially those with established RA [12, 13, 25, 26]. Our results also showed that disease duration was the only baseline factor associated with achieving CDAI remission. Considering the long disease duration in this study (mean 8.2 years), CDAI-LDA could be an alternative yet reasonable goal for our study subjects . Interestingly, DAS28-remission was attained in more than 70% of intervals, suggesting that the definition of ‘remission’ is heterogeneous in patients receiving TCZ . However, previous studies have also shown that DAS28 is unsuitable for assessing disease activity in patients on TCZ therapy due to the high weight on acute phase reactants for its scoring [28, 29].
In this study, TCZ dose tapering was performed in approximately half of the 1-year intervals after patients achieved CDAI-LDA. However, tapering the TCZ dose significantly increased the risk of failure to sustain the target at follow-up when compared with maintaining the standard-dose regimen. Furthermore, the dose tapering strategy did not reduce any adverse drug reactions, except for a slight decrease in the prevalence of hypercholesterolemia. We also showed that loss of CDAI-LDA at 1-year intervals was associated with higher HAQ-DI scores and poor disease control thereafter, which is in line with previous studies [30, 31]. Although tapering TCZ dose may reduce direct medical costs, higher disease activity and impaired physical function would increase the indirect cost related to work disability [32, 33]. Hence, our results suggest that the benefit of tapering TCZ dose does not overweigh the potential negative outcomes.
However, although tapering TCZ in overall showed lower efficacy than standard-dose treatment, it is noteworthy that approximately 85% of 1-year intervals in the tapering group maintained the target. This suggests that tapering strategy could be an effective option in certain subgroup of the patients. Unfortunately, we could not identify clinical factors predicting successful maintenance of CDAI-LDA after tapering TCZ in this study. We were not able to investigate the efficacy of tapering TCZ dose after achieving CDAI remission due to the small number of intervals achieving the target after one year of standard-dose TCZ treatment (n = 54). Nevertheless, the low rate of CDAI remission raises the question of whether tapering TCZ dose after achieving sustained remission would be the proper strategy in real-world clinical practice. Further studies would be necessary to help select patients who could sustain remission or LDA after tapering TCZ.
This study has some limitations. First, as patients in the KOBIO-RA cohort were followed up annually, the disease activity measured may not represent the disease activity throughout the year. However, this study only included patients who were treated with TCZ for more than 1 year and achieved CDAI-LDA at the 1-year follow-up visit. As discontinuation of bDMARDs due to inefficacy usually occurs during the first year of treatment, it is less likely that the disease activity had fluctuated before the time point of the patient’s follow-up visit [34, 35]. Moreover, all patients receiving bDMARD treatment in South Korea were evaluated every 6 months to determine whether they fulfilled the EULAR response criteria . Second, since this was an observational study, the effect of tapering TCZ dose could be biased due to ‘confounding by indication’. Although we performed a longitudinal analysis to consider all clinical variables and their changes throughout follow-up, some unmeasured confounders such as patient’s and physician’s preferences could have influenced the results. Finally, we were not able to investigate the effect of tapering TCZ dose on radiographic progression due to the scope of this registry.
In conclusion, our study showed that tapering TCZ dose in patients with RA who achieved CDAI-LDA at one-year of TCZ treatment increased the risk of losing LDA and subsequently led to functional impairment. Our results indicate that TCZ dose should be tapered in patients with LDA with caution in daily clinical practice.