Original Article
Predicting Chronic Spontaneous Urticaria Symptom Return After Omalizumab Treatment Discontinuation: Exploratory Analysis

https://doi.org/10.1016/j.jaip.2018.04.003Get rights and content
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Background

Omalizumab is highly effective in controlling chronic spontaneous urticaria (CSU) symptoms; however, patients can experience symptom return on treatment discontinuation. Pivotal clinical trials have identified 2 categories of patients who experience symptom return: rapid and slow.

Objective

The objective of this study was to identify potential predictors of the speed of symptom return after stopping omalizumab treatment.

Methods

Phase III randomized controlled trial (RCT) data from ASTERIA I (n = 319; 6 × 4 weekly injections of omalizumab 75, 150, 300 mg or placebo; NCT01287117) and ASTERIA II (n = 323; 3 × 4 weekly injections of omalizumab 75, 150, 300 mg, or placebo; NCT01292473) were pooled to identify predictors of symptom return after stopping omalizumab treatment (16-week follow-up). The least absolute shrinkage and selection operator regularization regression model was used to select predictive variables, and relapse probability was represented using heatmap visualizations. Model accuracy was tested using data from the GLACIAL phase III RCT (n = 336; 6 × 4 weekly injections of omalizumab 300 mg or placebo; NCT0126493).

Results

Of 746 variables assessed, 2 were selected by the model as predictors of symptom return: baseline urticaria activity score over 7 days (UAS7) and early area above the curve (AAC; determined by plotting the UAS7 scores across time points). Results suggest that high baseline UAS7 and low UAS7 AAC (slow decrease of symptoms) indicate a higher probability of rapid symptom return than low baseline UAS7 and high UAS7 AAC.

Conclusions

These results suggest that the probability of rapid symptom return in patients with CSU who discontinue treatment with omalizumab can be estimated based on baseline UAS7 and early treatment response.

Key words

Chronic spontaneous urticaria
LASSO model
Urticaria activity score
Chronic urticaria
Symptom return
Omalizumab
Treatment discontinuation

Abbreviations used

AAC
Area above the curve
AUC
Area under the curve
BOCF
Baseline observation carried forward
CSU
Chronic spontaneous urticaria
CU
Chronic urticaria
LASSO
Least absolute shrinkage and selection operator
LOCF
Last observation carried forward
RCT
Randomized controlled trial
UAS
Urticaria activity score
UAS7
Urticaria activity score over 7 days

Cited by (0)

No funding was received for this work.

Conflicts of interest: M. Ferrer served in advisory boards for Genentech, and has received a research grant, advisory and speaker fees from Novartis. A. Giménez-Arnau was a Principal Investigator in the ASTERIA II and GLACIAL omalizumab studies, has served on advisory boards for Genentech, and has received a research grant, advisory and speaker fees from Novartis. D. Saldana, N. Janssens, M.-M. Balp, S. Khalil, and V. Risson are employees of Novartis.