Relapse Rates, Time-to-Flare, and Biomarker Predictors Following Omalizumab Gradual De-escalation versus Abrupt Discontinuation in Controlled Chronic Spontaneous Urticaria: A Systematic Review and Meta-Analysis of Randomized Controlled Trials and Observational Cohorts.

BACKGROUND

How best to discontinue omalizumab once chronic spontaneous urticaria (CSU) is well controlled remains unsettled, and whether to taper gradually or to stop abruptly is a recurring source of clinical uncertainty.

OBJECTIVE

We set out to quantify relapse rates, time-to-flare kinetics, and biomarker predictors following gradual omalizumab de-escalation as opposed to abrupt discontinuation.

METHODS

PubMed, Embase, and Cochrane CENTRAL were searched systematically through April 2026. A random-effects proportion meta-analysis (DerSimonian-Laird) spanned 13 independent study arms (N = 1,382 patients contributing to the relapse-proportion analysis, drawn from 5,130 patients reviewed across 11 studies). Shared control groups within multi-arm trials were weighted a priori. Prespecified subgroups contrasted gradual de-escalation-whether achieved by interval extension (IE) or dose reduction (DR)-with abrupt discontinuation, and the certainty of evidence was appraised using GRADE.

RESULTS

Across all studies, the pooled relapse rate was 39.5% (95% CI, 30.1%-49.7%). Gradual de-escalation was associated with a significantly lower relapse rate than abrupt discontinuation (31.2% [95% CI, 20.3%-44.7%] vs. 48.9% [95% CI, 37.0%-61.0%]; Qb = 8.12; P = .004), and dose reduction to 150 mg every 4 weeks yielded the lowest rate of all (23.3%; 95% CI, 9.2%-47.6%; I² = 50.4%). Several baseline features independently predicted relapse: a high total IgE (>90 IU/mL, P = .005; or ≥341 kU/L, Cox P < .001), blood eosinophils >0.15 × 10⁹/L (P = .043), concomitant angioedema (OR, 2.40; P = .004), and disease duration exceeding 2 years (HR, 0.81 for successful drug survival; P = .03). Although Egger's test fell short of conventional significance (reported P = .109), the large negative intercept-coupled with the well-recognized unreliability of this test in proportion meta-analyses-meant that small-study effects could not be excluded with confidence. A sensitivity analysis confined to homogeneous cohorts followed for at least 6 months reaffirmed the superiority of de-escalation (P = .008).

CONCLUSION

Gradual de-escalation of omalizumab is associated with an almost two-fold reduction in the risk of post-discontinuation relapse relative to abrupt stopping. Baseline total IgE and blood eosinophils emerge as pivotal, endotype-specific biomarkers for judging which patients are ready to stop.