Background Previous research has shown that cessation of TNFi in patients with established RA who are in sustained remission is associated with an increased risk of flare. However, it is still unknown whether the reintroduction of TNFi in those who flare following cessation has any effects on long term outcome.
Objectives 1-To assess the 12 month outcomes following cessation of TNFi in patients with established RA who are in sustained remission (DAS28 < 2.6) at baseline. 2- To compare patients who restated TNFi after unsuccessful cessation with those who continued treatment.
Methods Patients in sustained remission (DAS28 < 2.6) for ≥ 6 months who were on a combination of methotrexate (MTX) and TNFi as per NICE guidance were recruited. The biologic agent was stopped in patients who consented to remain on MTX monotherapy and treatment was restarted if a flare occurred (defined as >1.2 deterioration in DAS28 or worsening of symptoms requiring escalation of treatment). Clinical, serological, and imaging (ultrasound of hands and wrists) outcomes were undertaken at baseline and 12 months. Patients who continued on combination therapy throughout the 12 months (CONT) were compared to those who unsuccessfully stopped and then restarted TNFi due to flare (STOP).
Results 18 patients (mean age 53.8 years) out of a total of 69 were allocated to STOP arm and 51 (mean age 48.5 years) to CONT arm. Baseline characteristics were not different between the two groups. 15/18 (83.3%) of patients flared in the cessation group compared to 13/51 (25.5%) in those who continued the biologic (p<0.001). The median time to flare was significantly shorter in those who stopped the biologic (12 vs. 26 weeks, p < 0.001). Patients flared in the CONT group for various reasons including missing a treatment dose, but the majority of flares were mild and managed symptomatically, although one patient required a change of biologic due to secondary non-response. DAS28 remission rates at month 12 were significantly greater in CONT compared to STOP group (85.7% vs. 57.1%; OR 5.35 [95%CI 1.25-22.7], p=.023). Mean scores of DAS28 (1.82 v 2.28), SDAI (4.45 v 6.83), HAQ (.60 V .93), CRP (3.2 v 4.6), and power Doppler (2.18 v 3.82) all favoured patients who continued biologic, although the results were not statistically significant.
Conclusions Successful cessation of TNFi is rare in patients with established RA despite sustained remission at baseline. Re-introducing the biologic following flare is associated with poorer outcomes and lower rates of DAS28 remission at long term follow up when compared to continuing the treatment. The small sample size of STOP group in this study was due to the considerable risk of flare on cessation of the biologic, which made it unethical to continue recruiting into that arm. This may have affected the statistical significance of individual parameters other than DAS28 remission rates. It is unknown whether the failure to re-establish remission in some patients after TNFi re-introduction is related to development of drug antibodies during biologic holiday.
Disclosure of Interest C. Rakieh: None Declared, B. Saleem: None Declared, K. Takase: None Declared, J. Nam: None Declared, H. Keen: None Declared, R. Wakefield: None Declared, P. Emery Consultant for: Honoraria/Advisory Board: Abbot, Pfizer, Roche, Chugai, BMS, UCB, MSD
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