Dupilumab linked to fewer respiratory infections from asthma, chronic rhinosinusitis

Patients with moderate-to-severe asthma or chronic rhinosinusitis with nasal polyps experienced fewer respiratory infections with dupilumab, according to data published in The Journal of Allergy and Clinical Immunology: In Practice.

“The shared pathophysiology of asthma and CRSwNP has important implications for their diagnosis and management, particularly as they often occur together,” Bob Geng, MD, allergist and immunologist at Rady Children’s Hospital-San Diego and assistant clinical professor at University of California San Diego School of Medicine, and colleagues wrote. “This provides a compelling rationale for treatments directed at the underlying systemic inflammation in patients with either condition.”

The researchers performed a retrospective post-hoc analysis of the LIBERTY ASTHMA QUEST study, which comprised 1,897 patients with moderate-to-severe asthma treated with dupilumab (Dupixent; Sanofi, Regeneron; n = 1,263) or placebo (n = 634), and the LIBERTY NP SINUS-52 study, which comprised 447 patients with severe CRSwNP treated with dupilumab (n = 297) or placebo (n = 150).

In the QUEST study, patients treated with dupilumab had fewer respiratory tract infections (103.34 vs. 113.08 events per 100 person-years; RR = 0.78; 95% CI, 0.71-0.85), according to investigator reports. Patients treated with dupilumab also had fewer investigator-reported upper (RR = 0.77; 95% CI, 0.7-0.85) and lower (RR = 0.72; 95% CI, 0.59-0.87) respiratory tract infection events compared with controls.

The researchers found similar results among patients enrolled in the SINUS-52 study. Patients treated with dupilumab were less likely to have respiratory tract infection events than controls (69.13 vs. 111.68 per 100 person-years; RR = 0.62; 95% CI, 0.51-0.75), and they showed a 34% (RR = 0.66; 95% CI, 0.53-0.81) lower rate of upper and 49% (RR = 0.51; 95% CI, 0.3-0.86) lower rate of lower respiratory tract infections events.

Among patients with asthma, dupilumab significantly reduced the annualized rate of severe exacerbations compared with placebo both among patients who had experienced respiratory infections and those who had not (P < .0001 for both).

For those with CRSwNP, dupilumab reduced the proportion of patients requiring oral corticosteroids (OCS) to treat disease flares or symptoms compared with the placebo group (13.2% vs. 41.2%).

“The reduction in investigator-reported infections during treatment may have contributed to the reduction in exacerbations and corresponding decrease in need for OCS observed in dupilumab-treated patients,” Geng and colleagues wrote. “Alternatively, as corticosteroid use is a known risk factor for infections, the reduction in OCS use in patients treated with dupilumab vs. placebo could lead to the reduction in respiratory infections.”

The researchers noted the retrospective nature of the study as one limitation, along with the presence of respiratory infections being reported by the investigator and not necessarily supported by accompanying laboratory data.

They also noted that because allergic rhinitis is often confused with a sinus infection, it is possible that allergic flares in patients with CRSwNP could have been misclassified as respiratory infections.

“The exact mechanisms behind the reduced rate of investigator-reported respiratory infection observed in patients treated with dupilumab is an important area of future investigation,” the researchers concluded.