Combination of allergen immunotherapy, tezepelumab relieves nasal symptoms of cat allergy

The addition of tezepelumab to subcutaneous allergen immunotherapy for 1 year improved results in nasal allergen challenges for patients with cat allergies, according to a study published in The Journal of Allergy and Clinical Immunology.

Patients who used both tezepelumab (Tezspire, Amgen/AstraZeneca), a human monoclonal anti-thymic stromal lymphopoietin antibody, and subcutaneous allergen immunotherapy (SCIT) also experienced reductions in peak nasal symptoms a full year after treatment had stopped, whereas those results did not persist among patients who only received immunotherapy, the researchers wrote.

“We know from prior research that SCIT alone may only be partially effective in some patients, and it needs to be administered for a minimum of 3 years to induce lasting tolerance,” Jonathan Corren, MD, an allergist-immunologist at the David Geffen School of Medicine at UCLA, said in a press release.

“We found that combining tezepelumab plus SCIT resulted in a persistent significant reduction in allergen responsiveness 1 year after treatment was stopped, indicating that the combination treatment provided a degree of tolerance for patients with cat allergies,” he continued.

The study design

The randomized, double-blind CATNIP trial involved 121 patients aged 18 to 65 years with moderate to severe cat-induced allergic rhinitis between 2015 and 2019.

These patients received cat-specific SCIT plus tezepelumab (n = 32; median age, 27 years; 75% women; 65.6% white), SCIT alone (n = 31; median age, 28 years; 64.5% women; 90.3% white), tezepelumab alone (n = 30; median age, 27.5 years; 53.3% women; 80% white) or placebo (n = 28; median age, 26.5 years; 53.6% women; 85.7% white), administered weekly in increasing doses for approximately 12 weeks followed by monthly maintenance injections until week 48.

Patients underwent nasal allergen challenges (NACs) with cat allergen extracts via nasal spray at baseline and at weeks 26, 52, 78 and 104. During these challenges, the researchers recorded total nasal symptom scores (TNSS) and peak nasal inspiratory flows (PNIF) at 5, 15, 30 and 60 minutes and then hourly up to hour 6.

Skin prick tests, intradermal skin tests (IDST) and nasal brushing were conducted as well. Also, the researchers measured the serum levels of IgE, IgE4 and total IgE specific to cat dander as well as IL-5 and IL-13 serum.

Primary, secondary endpoints

At the end of treatment at 52 weeks, the group on combination treatment had significantly lower TNSS area under the curve (AUC) at 0 to 1 hour and TNSS peak scores at 0 to 1 hour than the group taking SCIT alone, which the researchers said indicated that the addition of tezepelumab improved SCIT’s efficacy.

Researchers also saw improvements in these endpoints at 52 weeks for the group assigned SCIT alone compared with the placebo group, but there were no significant differences in these values between the tezepelumab-alone and placebo groups.

At week 104, a year after treatment ended, researchers observed no significant differences between SCIT with tezepelumab and SCIT alone in TNSS AUC at 0 to 1 hour, which served as the study’s primary endpoint. But patients assigned the combination had significantly lower TNSS peak scores at 0 to 1 hour, indicating that there was a persistent reduction in allergen responsiveness a full year after therapy had stopped, compared with the patients assigned SCIT alone, tezepelumab alone and placebo.

Researchers did not see a significant improvement in either endpoint between the groups receiving SCIT or tezepelumab alone and the placebo group.

The groups on combination therapy and SCIT alone did not have any significant differences in PNIF, early and late responses to IDST or early response to SPT at weeks 52 or 104.

In total, nasal symptoms decreased by 36% by the end of treatment and 24% a year later among the combination group compared with the SCIT group.

Serum studies, adverse events

Additionally, the group on combination therapy had lower serum concentrations for IL-5 and IL-13 than the group on SCIT alone at week 52, with a similar reduction among the patients who only received tezepelumab.

At week 104, IL-5 and IL-13 levels had increased but were still significantly lower than their baseline figures in patients assigned the combination or tezepelumab alone.

The patients in the combination and SCIT groups showed a decline in cat-specific IgE that plateaued in the SCIT group at week 52, but it continued to decline for the combination and tezepelumab-alone groups through week 104, with similar changes for serum total IgE.

The researchers also found alterations in type 2 genes among patients in the combination group.

“One year after stopping all treatments, the combination of tezepelumab plus immunotherapy resulted in a reduction in expression of a number of genes which control allergic inflammation,” Corren said. “Most important of these were genes which control the production of mast cell mediators, particularly tryptase.”

There were no significant differences in adverse events between the treatment groups, although the combination and SCIT-alone groups experienced similar increases in local and systemic reactions.

The researchers also said that there were no adverse events related to tezepelumab when used alone or in the combination group, and there were four total serious adverse events with no significant differences between these two groups.

Conclusions, next steps

Overall, the researchers concluded, a year of therapy with SCIT and tezepelumab was significantly more effective than SCIT alone in reducing the nasal response to allergen challenges for up to a full year after treatment.

The researchers next will analyze the data to understand how the combination works at the cellular level to design larger trials exploring more health outcomes and identifying who may benefit the most from this treatment.

References:

• Adding Tezepelumab to allergen immunotherapy reduces nasal symptoms in patients with cat allergies. https://www.aaaai.org/About/News/News/tezepelumabs. Published Oct. 10, 2022. Accessed Oct. 12, 2022.
• Monoclonal antibody improves cat allergen immunotherapy. https://www.niaid.nih.gov/news-events/monoclonal-antibody-improves-cat-allergen-immunotherapy. Published Oct. 11, 2022. Accessed Oct. 12, 2022.