Discontinuation of adalimumab after achieving remission in patients with established rheumatoid arthritis: 1-year outcome of the HONOR study

Abstract

Objectives: To investigate the possibility of discontinuing adalimumab (ADA) for 1 year without flaring (DAS28-erythrocyte sedimentation rate (ESR) ≥3.2), and to identify factors enabling established patients with rheumatoid arthritis (RA) to remain ADA-free.

Methods: Of 197 RA patients treated with ADA+methotrexate (MTX), 75 patients who met the ADA-free criteria (steroid-free and sustained DAS28-ESR remission for 6 months with stable MTX doses) were studied for 1 year.

Results: The mean disease duration and DAS28-ESR score in 75 patients was 7.5 years and 5.1 at baseline, respectively. The proportion of patients who sustained DAS28-ESR <2.6 (48%) and DAS28-ESR <3.2 (62%) for 1 year were significantly lower in the ADA discontinuation group than in the ADA continuation group; however, in patients with deep remission (DAS28-ESR ≤1.98) identified by receiver operating characteristics analysis following logistic analysis, these rates increased to 68% and 79%, respectively, with no significant difference between both groups. Remarkably, ADA readministration to patients with flare was effective in returning DAS28-ESR to <3.2 within 6 months in 90% and 9 months in 100% patients; among the patients who sustained DAS28-ESR <3.2 during ADA discontinuation, 100% remained in structural remission and 94% in functional remission.

Conclusions: The possibility of remaining ADA-free for 1 year was demonstrated in established patients with RA with outcomes that ADA can be discontinued without flaring in 79% patients with deep remission, with similar rates in the ADA continuation group, and showed no functional or structural damage in patients with DAS28-ESR <3.2. ADA readministration to patients with flare during ADA discontinuation was effective.

Keywords: Anti-TNF; Rheumatoid Arthritis; Treatment.

Figure 1

Clinical outcomes evaluated by DAS28- erythrocyte sedimentation rate (ESR) or simplified disease activity index (SDAI) after ADA discontinuation and effects of ADA readministration to patients with flare. (A) shows the proportion of patients with sustained remission and low disease activity (LDA) evaluated using DAS28-ESR (DAS28) or SDAI. Each rate at 1 year after ADA discontinuation was compared with that in the ADA continuation group (Fisher's exact test). (B) shows the time course of changes in DAS28 including rescues of patients with flare (Left: ADA initiation to discontinuation, Middle: ADA discontinuation to 1 year later, Right: Flare to 6 months following rescue with methotrexate (MTX) or ADA). **p<0.01: ADA discontinuation versus ADA continuation using DAS28. In the comparison using SDAI, no significant difference was observed (p=0.4502 for remission, p=0.5690 for under LDA).

Figure 2

Clinical outcomes in patients with deep remission and influence of the degree of remission. The percentages of patients in remission or with low disease activity (LDA) at 1 year after fulfilling the ADA-free criteria were investigated in patients with deep remission and compared between the ADA discontinuation and continuation groups, using a cut-off value of DAS28-4 erythrocyte sedimentation rate (ESR) ≤1.98 identified using receiver operating characteristics (ROC) analysis. No significant differences were observed between the groups (p=0.228 for DAS28-ESR<2.6, p=0.649 for DAS28-4ESR<3.2, p=0.707 for simplified disease activity index (SDAI) ≤3.3, p=0.545 for SDAI≤11; Fisher's exact test). (B) shows disease activity at 1 year after ADA discontinuation according to the difference in the degree of remission (deep or mild) when ADA was discontinued. ***p<0.001: deep (DAS28 ≤1.98) versus mild (1.98

Figure 3

Functional and structural remission in patients with sustained or failed low disease activity (LDA). (A) and (B) show values of health assessment questionnaire-disability index (HAQ-DI) and ΔmTSS in patients with sustained LDA (n=31) at 1 year after ADA discontinuation or failed LDA (n=21) when evaluated by DAS28-4 erythrocyte sedimentation rate (ESR). The percentages show the proportion of patients with sustained functional remission (HAQ<0.5) and structural remission (ΔmTSS<0.5). p Values by Kruskal–Wallis test; mTSS, modified total sharp score.