Adding Tezepelumab to SCIT Improves Response to Nasal Cat Allergen Challenge

The addition of tezepelumab to subcutaneous allergen immunotherapy (SCIT) for 1 year was associated with a significant decrease in the nasal response to allergen challenge compared with immunotherapy alone, investigators reported in the Journal of Allergy and Clinical Immunology.

The randomized, double-blind, placebo-controlled ITN057AD CATNIP trial (ClinicalTrials.gov Identifier: NCT02237196) was conducted at 9 US sites. Eligible participants were aged 18 to 65 years with a minimum 2-year clinical history of moderate to severe cat-induced allergic rhinitis with a positive skin prick test to cat extract and a positive nasal allergen challenge (NAC) for cat allergy, defined as a total nasal symptom score (TNSS) of at least 8 on a 12-point scale.

A total of 121 participants were enrolled and randomly assigned to 4 groups receiving: (1) SCIT plus tezepelumab (n = 32; median age, 27.0 years; 75% female); (2) SCIT plus placebo (n = 31; median age, 28.0 years; 64.5% female); (3) tezepelumab plus placebo (n = 30; median age, 27.5 years; 53.3% female); or (4) placebo, using a double-dummy design (n = 28; median age, 26.5 years; 53.6% female).

Subcutaneous cat immunotherapy (10,000 BAU/mL) or matched placebo subcutaneous injections were administered weekly in increasing doses for about 12 weeks, followed by a monthly maintenance injection (4000 BAU or the maximum tolerated dose) until week 48. Tezepelumab (700 mg IV) or matched placebo was administered 1 to 3 days before SCIT or placebo once every 4 weeks through week 24, followed by before or on the same day as SCIT or placebo injection through the end of dosing at week 48.

The patients had an NAC with cat allergen extract using a nasal spray at screening, baseline, and at weeks 26, 52, 78, and 104. The primary endpoint was the TNSS area under the curve (AUC) 0 to 1 hour at week 104.

Of the cohort, 86 participants completed the trial, and 76 met the per protocol population criteria. No significant difference was observed at week 104 in the primary endpoint TNSS AUC 0 to 1 hour for the SCIT/tezepelumab group vs the SCIT alone group during NAC. Also at week 104, the secondary endpoint TNSS peak 0 to 1 hour was significantly lower in patients who received SCIT/tezepelumab vs SCIT alone, which indicates a persistent decrease in allergen responsiveness 1 year after stopping treatment.

At week 104, the TNSS peak 0 to 1 hour was significantly lower in participants who received SCIT/tezepelumab compared with participants who received either tezepelumab monotherapy or placebo. No significant differences occurred between the SCIT or tezepelumab monotherapy groups compared with the placebo group for either TNSS area AUC 0 to 1 hour or TNSS peak 0 to 1 hour at 104 weeks.

After 52 weeks, the SCIT/tezepelumab group had significantly lower TNSS AUC 0 to 1 hour and TNSS peak 0 to 1 hour vs the SCIT alone group, which indicates improvement in SCIT efficacy with the addition of tezepelumab. The SCIT alone group had significantly lower TNSS AUC 0 to 1 hour and TNSS peak 0 to 1 hour values vs the placebo group. No significant differences were found at week 52 in TNSS AUC 0 to 1 hour and peak 0 to 1 hour in the tezepelumab monotherapy group vs the placebo group.

Total adverse events were comparable among the treatment groups. The SCIT/tezepelumab and SCIT monotherapy groups had an increase in local and systemic reactions, with no differences between the 2 groups.

“These results highlight the important role of thymic stromal lymphopoietin in nasal responsiveness to allergen challenge and demonstrate that the addition of tezepelumab to SCIT improves both the magnitude and duration of clinical and immunologic changes induced with allergen immunotherapy,” said the investigators.

Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.