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We appreciate the interest of García and Abud-Mendoza in our article on tapering towards disease-modifying antirheumatic drug (DMARD)-free remission (DFR), and we would like to respond to the points that were brought up.1 2
Garciá and Abud-Mendoza1 proposed two ways to reduce the amount of flares during tapering of medication, namely (1) the (continuous) use of low-dose glucocorticoids (GCs) and (2) the use of ultrasound to detect subclinical synovitis before a flare occurs. Although the (continuous) use of low-dose GCs might help in tapering DMARDs, including biologicals, to lower dosages without experiencing a flare, it does not alter the DFR rates because, in our opinion, patients are only in DFR if they do not use any DMARD, including GCs. However, we believe that DFR is not a suitable treatment goal because only 15% of patients with rheumatoid arthritis (RA) reached this goal and, therefore, tapering strategies should be targeted at finding the lowest possible DMARD dosages without changing the disease activity state. Aforementioned reasoning reraises the question what the best tapering order is, which should be addressed for a clinical (i.e., long-term side effects and change at flare), patient (ie, preference) as well as a societal perspective (i.e., healthcare and productivity costs).
Garciá and Abud-Mendoza1 also propose the use of ultrasound to reduce the amount of flares during tapering. During tapering of treatment, patients might develop subclinical synovitis, without the occurrence of a flare, which might be an indication to stop tapering or intensify treatment. Several studies have already shown that subclinical synovitis is associated with tapering failures, however, the implementation in daily practice is still unclear.3 4 Practical issues remain, such as whether we should perform an ultrasound at each possible tapering moment and/or which joints should be assessed. Within the Taperingstrategies in Rheumatoid Arthritis (TARA) trial, we also made ultrasounds at each visit in the first year of follow-up, and we found that only one-third of the patients with RA with a well-controlled disease were also in ultrasound remission at baseline.5 So, future research is needed to further explore the usefulness of ultrasound, in daily practice, and especially in predicting disease flares during tapering of treatment.
Finally, García and Abud-Mendoza1 asked for a subanalyses of the TARA trial in which DFR rates are compared between both tapering strategies, namely, gradually tapering the conventional synthetic DMARD (csDMARD) followed by the TNF-inhibitor or vice versa, in patient with RAs using one csDMARD at baseline. No differences were found in the baseline characteristics, and also no difference was found in the ability to reach DFR taking only patients into account using mono-csDMARD therapy at baseline (p=0.65, table 1). Moreover, we previously analysed whether patients with multiple csDMARDs were more likely to complete the tapering protocol, and also found no differences (β=−0.70, p=0.08, table 1).2
To conclude, we agree with Garciá and Abud-Mendoza1 that current tapering strategies are far from perfect, because of high flare rates and low DFR rates. An individualised tapering strategy is, therefore, preferred. In our opinion, the first step would be to predict a flare before its occurrence using a broad range of outcomes such as clinical outcomes, patient-reported outcomes, biomarkers and imaging.
We thank the participating patients in the TARA trial for their willingness to contribute to the study and for their cooperation. We thank all rheumatologists from the participating centres. We also thank all study-nurses, datamanagers, laboratory personnel, coinvestigators and others who were involved with the TARA study.
Handling editor Josef S Smolen
Contributors Both authors were equally involved in interpretation of the data and for drafting, revising, and approving the final submitted manuscript.
Funding The TARA trial was supported by ZonMw (grant number 171102014).
Competing interests None declared.
Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.
Patient consent for publication Not required.
Ethics approval Research ethics approval for the TARA trial was obtained from METC Erasmus MC (MEC-2011-141, NL35282.078.11).
Provenance and peer review Commissioned; internally peer reviewed.
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