麻豆传媒

Subcutaneous immunotherapy treatment (SCIT) for reducing cat allergy symptoms appeared to be more effective and longer lasting with the help of tezepelumab (Tezspire), a monoclonal antibody recently approved for severe asthma, results from a phase I/II trial suggested.

While the randomized CATNIP trial failed to meet its primary endpoint -- a difference in total nasal symptom score (TNSS) when participants were exposed to cat allergen extract a year after stopping treatment -- a reduction in peak nasal symptoms was observed when tezepelumab was added to SCIT, reported Jonathan Corren, MD, of David Geffen School of Medicine in Los Angeles, and colleagues.

Peak TNSS scores with the combined therapy were significantly lower both after a year of treatment, as well as a year after stopping therapy, according to the findings:

• Mean difference at 52 weeks: -2.0 (95% CI -3.4 to -0.5, P=0.008)
• Mean difference at 104 weeks: -1.8 (95% CI -3.5 to -0.2, P=0.026)

"Patients receiving the combination of SCIT and tezepelumab demonstrated a significant reduction in peak nasal symptoms one year after stopping therapy, indicating partial persistence of tolerance," the group wrote in the . "This effect was accompanied by changes in a large number of type 2 genes with alterations in nasal mast cell function perhaps being most important."

Corren and his fellow researchers said the four-arm trial showed that the combination therapy worked more quickly, was more effective, and lasted longer than SCIT alone, tezepelumab alone, or placebo.

Tezepelumab blocks the thymic stromal lymphopoietin protein, a secretion that is initiated when organs or skin lining the nose and lungs are responding to signals that there is potential danger. In the case of cat dander, this is an unnecessary over-reaction that inflames airways and leads to allergic rhinitis symptoms, the researchers explain.

CATNIP's "results show for the first time that adding a cytokine inhibitor to allergy shots can reduce allergic rhinitis symptoms for an extended period after just one year of treatment," the researchers explained in a press sent out by the National Institutes of Health, the study's funder.

"People with chronic allergy symptoms may suffer from reduced productivity and quality of life," said Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, in the release. "Developing allergen immunotherapy regimens that work better and more quickly than those currently available would provide much-needed relief for many people."

NIH noted that these trial results have informed a phase II trial underway for using tezepelumab plus oral immunotherapy to treat food allergies. The NIH is funding that trial too.

CATNIP randomized 121 adults from nine U.S. centers to receive 700 mg intravenous tezepelumab plus SCIT (n=32), tezepelumab plus placebo shots (n=30), SCIT plus placebo (n=31), or a combined placebo (n=28). All participants were blinded.

To test each treatment, participants received a "spritz" of cat allergen extract in both nostrils six times during the 2-year study period, followed by testing of their nasal symptoms and airflow. The researchers also collected blood and nasal cell samples. The primary outcome was TNSS area under the curve for the first hour after the challenge at 104 weeks.

Overall, TNSS was significantly lower for participants on SCIT plus the monoclonal antibody after stopping treatment at 1 year compared with SCIT alone, but not a year after that:

• Mean difference at 52 weeks: -1.0 (95% CI -1.8 to -0.1, P=0.028)
• Mean difference at 104 weeks: -0.5 (95% CI -1.5 to 0.5, P=0.314)

Adverse events occurred in 78.5% of participants overall, but no significant differences were reported between treatment groups, though systemic and local reactions were more frequently observed in the SCIT arms.

Comment