Dupilumab

Medical uses

Dupilumab is indicated for the treatment of moderate-to-severe atopic dermatitis; moderate-to-severe asthma; chronic rhinosinusitis with nasal polyps; eosinophilic esophagitis; prurigo nodularis; and chronic obstructive pulmonary disease. It has been shown to be effective at treating aspirin-exacerbated respiratory disease (AERD), a typically difficult to treat condition where aspirin intolerant patients have both chronic rhinosinusitis with nasal polyps and asthma.

History of extension of indications

In May 2022, the indication was updated to include the treatment of eosinophilic esophagitis in people aged twelve years of age and older weighing at least 40 kg.

In September 2022, the indication was updated to include the treatment of adults with prurigo nodularis (PN).

In March 2023, the European Medicines Agency approved dupilumab for the treatment of severe atopic dermatitis in children aged six months to five years who are candidates for systemic therapy.

In September 2024, the indication was updated to include the treatment of chronic rhinosinusitis with nasal polyps for adolescents, and chronic obstructive pulmonary disease.

In April 2025, the indication was updated to include the treatment of chronic spontaneous urticaria. In June 2025, an additional indication for treatment of bullous pemphigoid was also approved.

Side effects

Eosinophilia is a known side effect of dupilumab. Injection site reactions such as redness and pain are common, occurring in approximately 11.4% of cases. Dupilumab can cause allergic reactions, conjunctivitis, and keratitis and, due to its immunosuppressive effects, reactivation of cold sores. In clinical trials, people receiving dupilumab had decreased levels of T helper cells. Arthralgias (joint pain) and psoriasis have also been reported as side effects.

Pharmacology

Mechanism of action

Dupilumab binds to the alpha subunit of the interleukin-4 receptor (IL-4Rα), making it a receptor antagonist. Through blockade of IL-4Rα, dupilumab modulates signaling of both the interleukin 4 and interleukin 13 pathways.

Pharmacokinetics

Dupilumab shows a non-linear rate in regard to the target. Dupilumab is also reported to have a bioavailability of 64%, with the average concentration occurring one week after injection.

Society and culture

Legal status

The US Food and Drug Administration (FDA) granted the application for dupilumab priority review designation and in March 2017, the FDA approved dupilumab injection to treat adults with moderate-to-severe eczema.

The FDA granted the application breakthrough therapy designation.

Cost

In a 2020 cost-effectiveness study dupilumab was inferior to endoscopic sinus surgery (ESS): At a 36-year time horizon dupilumab treatment cost $536,420.22 and produced 8.95 QALYs (quality-adjusted life years), while ESS cost roughly one tenth at $50,436.99 and produced 9.80 QALYs.

History

Regeneron Pharmaceuticals and Sanofi Genzyme jointly developed dupilumab, the latter of which provided 130 million dollars to Regeneron for research and development towards monoclonal antibodies. Phase II trials for asthma treatment showed increased lung function with increased forced expiratory volume for patients.

In October 2016, Regeneron completed a phase III trial comparing dupilumab with topical corticosteroids, in which subjects had a larger decrease in symptoms with both dupilumab and topical steroids than with steroids alone. In these trials 38% and 36% of patients respectively, met the primary efficacy goal of the trial, compared to 8% and 10% under placebo.

The efficacy and safety of dupilumab in eosinophilic esophagitis was studied in a randomized, double-blind, parallel-group, multicenter, placebo-controlled trial, that included two 24-week treatment periods (Part A and Part B) that were conducted independently in separate groups of participants. In Part A and Part B, participants received either placebo or 300 milligrams of dupilumab every week. The two primary measurements of efficacy were the proportion of participants who achieved a certain level of reduced eosinophils in the esophagus at week 24, as determined by assessing participants' esophageal tissue under a microscope, and the change in the participant-reported Dysphagia Symptom Questionnaire (DSQ) score from baseline to week 24. The DSQ is a questionnaire designed to measure difficulty swallowing associated with eosinophilic esophagitis, with total scores ranging from 0 to 84; higher DSQ scores indicate worse symptoms.

The efficacy and safety of dupilumab to treat prurigo nodularis among adults were evaluated in two clinical trials, EFC16459 (PRIME) and EFC16460 (PRIME2). Each trial evaluated 300 mg of dupilumab administered every 2 weeks following an initial dose of 600 mg. The treatment lasted for 24 weeks. Effectiveness was mainly assessed by the proportion of subjects whose itchy skin (pruritus) improved by more than four points on the Worst Itch Numeric Rating Scale, the proportion of subjects who achieved score of 0 or 1 on Investigator's Global Assessment PN-stage scale (the equivalent of 0-5 nodules), and the proportion of subjects who achieved a response on both scales at week 24.

References

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