Background/Purpose:

Treatment with TNF blockers, once started as therapy for RA, is usually continued indefinitely. Information about the possibility to discontinue anti-TNF therapy in RA patients who have obtained remission is limited. If remission could be sustained after cessation of anti-TNF therapy, this would have vast clinical as well as economic implications. The objective of the ADMIRE trial was to assess the possibility of discontinuing adalimumab treatment while maintaining remission in RA patients in stable remission (DAS 28<2.6 for ≥3 months) on combination therapy with adalimumab + methotrexate (MTX).

Methods:

A randomized, controlled, open label pilot study of RA patients in stable remission treated with adalimumab + MTX. Patients were randomized in a 1:1 ratio to continue with adalimumab + MTX (arm AM) or to discontinue the biologic agent and continue with MTX monotherapy (arm M) for 52 weeks. Flare was defined as DAS28>2.6 or an increase in DAS28 (DeltaDAS28) of more than 1.2 from baseline at any time. Patients in arm M with a flare restarted adalimumab. The primary endpoint was the proportion of patients in remission at week 28 in both arms. Nonresponder imputation (ie, ”flare” imputed) was performed for patients with no available DAS28 at week 28 (this included most patients who had a flare in the M group and restarted adalimumab).

Results:

Thirty-three patients were enrolled in the study and were randomized to arm AM (n=17) and arm M (n=16). One patient in arm AM was excluded (did not fulfill inclusion criteria) and one patient in arm M was excluded due to protocol violation. The median (IQR) age of patients was 61 (53–65) years, median (IQR) disease duration was 8 (5–15) years and 67% were female. Median (IQR)  DAS28 was 1.86 (1.53-2.39) and MTX dose was 20 mg/w (12.5-20) at baseline. At the end of 28 weeks, 15/16 patients (94%) and 5/15 patients (33%) in arms AM and M, respectively, were in remission (P=0.001). In the M group, 3/15 patients were in remission on MTX only. The proportion of patients with a flare during the first 28 weeks in the AM and M arms was 50% (8/16) and 80% (12/15), respectively (P=0.08). The number of patients in the AM and M arms with at least one DeltaDAS28>1.2 during the first 28 weeks was 1/16 (6%) and 8/15 (53%), respectively (P=0.005). Other results from secondary analyses are shown in Table 1.

Table 1. Primary and secondary efficacy endpoints.

Outcome	Arm AM (adalimumab + MTX) n=16	Arm M (MTX) n=15	Difference between groups*
No. (%) of patients in remission at week 28	15/16 (94%)	5/15 (33%)	0.001
No. (%) of patients with at least 1 flare during first 28 weeks	8/16 (50%)	12/15 (80%)	0.08
No. (%) of patients with at least 1 DAS28>2.6 during first 28 weeks	8/16 (50%)	11/15 (73%)	0.2
No. (%) of patients with at least 1 DeltaDAS28>1.2 during first 28 weeks	1/16 (6%)	8/15 (53%)	0.005
No. (%) of patients with at least 1 DeltaDAS28>0.6 during first 28 weeks	8/16 (50%)	13/15 (87%)	0.04
No. (%) of patients with at least 1 DAS28>2.6 AND DeltaDAS28>1.2 during first 28 weeks	1/16 (6%)	7/15 (47%)	0.01
No. (%) of patients with at least 1 DAS28>2.6 AND DeltaDAS28>0.6 during first 28 weeks	5/16 (31%)	11/15 (73%)	0.02
Relapse-free survival (mean weeks)	22 (95% CI, 18–26)	16 (95% CI, 10–21)	0.05

*Fisher exact test for categorical variables; log-rank (Mantel-Cox) test for survival analysis.

Conclusion:

In this pilot study, remission was rarely maintained in patients with long standing RA who discontinued adalimumab. Compared to patients who continued combination therapy, the proportion in sustained remission was significantly lower for the primary and most secondary endpoints. Adalimumab discontinuation may be feasible in only a minority of patients with established RA in stable clinical remission on adalimumab + MTX.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-multicenter-randomized-controlled-open-label-pilot-study-of-the-feasibility-of-discontinuation-of-adalimumab-in-rheumatoid-arthritis-patients-in-stable-clinical-remission/