The quality of evidence is downgraded by inconsistency (statistical heterogeneity).
A Cochrane review [Abstract] 1 included 14 studies with a total of 3 315 subjects with early as well as established rheumatoid arthritis (RA). The majority of subjects were female with mean ages between 47 and 60. Six studies (n=1 148) examined anti-TNF dose reduction compared with anti-TNF continuation, 8 studies (n=2 111) examined anti-TNF discontinuation compared with anti-TNF continuation (3 studies assessed both anti-TNF discontinuation and dose reduction), and 3 studies assessed disease activity-guided anti-TNF dose tapering (n=365) in people with low disease activity. The studies included data on all anti-TNF agents, but primarily adalimumab and etanercept. Study durations ranged from 6 months to 3.5 years.
Fixed-dose reduction of anti-TNF (especially etanercept) in people with RA with at least 3 to 12 months of low disease activity was comparable with continuing the standard dose with regard to mean disease activity (DAS28: MD 0.06, 95% CI −0.11 to 0.24; 2 studies, n=501), the proportion of participants remaining in remission (RR 1.01, 95% CI 0.80 to 1.28, statistical heterogeneity I2 =73%; 2 studies, n=612), and mean function (Health Assessment Questionnaire Disability Index, HAQ-DI: MD 0.09, 95% CI 0.00 to 0.19; 2 studies, n=501) after 26 to 52 weeks. Dose reduction probably slightly increased the proportion of participants with minimal radiographic progression after 52 weeks (RR 1.22, 95% CI 0.76 to 1.95; 2 studies, n=553), although the difference was not statistically significant. Dose reduction caused little or no difference in number of serious adverse events and withdrawals due to adverse events.
Anti-TNF discontinuation (without disease activity-guided restarting of treatment) was an inferior compared with continuation of anti-TNF in terms of disease control (DAS28: MD 0.96, 95% CI 0.67 to 1.25, statistical heterogeneity I2 =61%; 2 studies, n=733), proportion of participants remaining in remission, minimal radiographic damage after 52 weeks (RR 1.69, 95% CI 1.10 to 2.59; 3 studies, n=549), and function (HAQ-DI: MD 0.18, 95% CI 0.05 to 0.31, statistical heterogeneity I2 =79%; 4 studies, n=1 498). The authors state that discontinuation should not be attempted without regular assessment of disease activity, setting a treatment goal, and reinstatement of treatment when necessary.
Anti-TNF disease activity-guided dose tapering resulted in little or no difference in mean disease activity score after 72 to 78 weeks (DAS28: MD 0.25, 95% CI -0.17 to 0.67, statistical heterogeneity I2 =70%; 3 studies, n=357), no difference in the proportion of participants with persistent remission after 18 months (RR 0.89, 95% CI 0.75 to 1.06; 1 study, n=180). It tended to slightly increase the proportion of participants with minimal radiographic progression (RR 1.45, 95% CI 0.77 to 2.73, statistical heterogeneity I2 =59%; 2 studies, n=312), and probably led to a slight deterioration of function after 18 months (MD 0.2, 95% CI -0.02 to 0.42; 1 study, n=123), although the differences were not statistically significant. The authors state that because disease activity-guided dose tapering provides the opportunity to find the lowest effective dose for each individual patient and to discontinue treatment as the final step of the tapering process, this may be the most cost-effective and feasible approach in clinical practice.
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