Abstract Session
Vasculitis
Peter Merkel, MD,MPH
University of Pennsylvania
Philadelphia, Pennsylvania, United States
No financial relationships with ineligible companies to disclose
Among the 140 patients in the trial, airway-related manifestations commonly reported at baseline included wheeze (24.3% of patients), paranasal sinus involvement (17.9%), and bloody nasal discharge/crusts/ulcers/granulomata (14.3%), all of which decreased rapidly in frequency and affected < 5% of patients by Week 52, despite substantial OGC reductions during the study (Figure 1). The frequency of non-airway-related manifestations (including manifestations such as arthralgia/arthritis, sensory peripheral neuropathy, myalgia, and mononeuritis multiplex) also decreased to < 2% of patients by Week 52. Cutaneous manifestations were infrequent at baseline, and disappeared by Week 52. No cardiovascular manifestations were reported at baseline or during the trial. Three central nervous system manifestations (sensorineural hearing loss) were reported at baseline but not subsequently during the trial. There were 22 new items of damage recorded during the double-blind period (Figure 2). Of these, only 4 (benralizumab, n=2; mepolizumab, n=2) were increases related to persistent disease activity: chronic sinusitis/radiotherapy damage, n=2; peripheral neuropathy, n=1; nasal polyps, n=1. None of these were new manifestations for the patients.
Conclusion: Eosinophil-targeting biologic agents appear to be rapidly effective at reducing and controlling both airway- and non-airway-related manifestations of EGPA. In the 52-week double-blind period of the MANDARA trial, few patients experienced worsening of their disease that progressed to organ damage, suggesting that these therapies may be effective both on airway-related and non-airway-related manifestations of EGPA, despite substantial OGC reductions.
Figure 1. Summary of select manifestations of eosinophilic granulomatosis with polyangiitis during the 52-week double-blind phase of the MANDARA trial
Corresponding proportion of patients (%) is shown beneath each bubble. Manifestations are categorized as per the Birmingham Vasculitis Activity Score.
ENT, ear, nose, throat; hpf, high power field; RBC, red blood cells.
Figure 2. Summary of accumulation of items of damage in patients with eosinophilic granulomatosis with polyangiitis during the 52-week double-blind phase of the MANDARA trial
Corresponding proportion of patients (%) is shown beneath each bubble.
a EGPA-related items of the Birmingham Vasculitis Activity Score that progressed to the VDI: ENT (chronic sinusitis/radiological damage; n=2, one from bloody nasal discharge/crusts/ulcers/granulomata and one from paranasal sinus involvement); neuropsychiatric (peripheral neuropathy; n=1 from mononeuritis multiplex); and other (nasal polyps; n=1 from bloody nasal discharge/crusts/ulcers/granulomata and paranasal sinus involvement).
DBP, diastolic blood pressure; ENT, ear nose and throat.
P. Merkel: AbbVie/Abbott, 2, 5, Amgen, 2, 5, argenx, 2, AstraZeneca, 2, 5, Boehringer Ingelheim, 3, 5, Bristol Myers Squibb, 2, 5, Cabaletta, 2, ChemoCentryx, 2, 5, CSL Behring, 2, Dynacure, 2, Eicos, 5, Electra, 5, EMDSerano, 2, Forbius, 2, 5, Genentech/Roche, 2, 5, Genzyme/Sanofi, 2, 5, GSK, 2, 5, HiBio, 2, Immagene, 2, InflaRx, 2, 5, Jannsen, 2, Kiniksa, 2, Kyverna, 2, Magenta, 2, MiroBio, 2, Neutrolis, 2, Novartis, 2, NS Pharma, 2, Pfizer, 2, Q32, 2, 11, Regeneron, 2, Sanofi, 5, Sparrow, 2, 11, Takeda, 2, 5, Talaris, 2, UpToDate, 9, Visterra, 2; D. Jayne: Amgen, 2, 6, AstraZeneca, 2, 6, Aurinia, 4, Boehringer Ingelheim, 2, 6, Bristol-Myers Squibb(BMS), 2, 6, ChemoCentryx, 2, 6, Chinook, 1, CSL Vifor, 2, GSK, 1, 2, 6, Novartis, 2, 6, Roche, 2, 6, Takeda, 1, 2, 6, Vifor Pharma, 2, 6; U. Specks: Amgen, 2, 5, Argenx, 2, AstraZeneca, 1, 2, 5, Boehringer-Ingelheim, 1, 2, Bristol-Myers Squibb(BMS), 5, CSL Vifor, 1, Genentech, 5, GlaxoSmithKline(GSK), 5, Northstar Medical Radioisotopes, 5, Novartis, 5, NS Pharma, 5; C. Pagnoux: AstraZeneca, 1, GlaxoSmithKline, 1, 2, 5, 6, Otsuka, 1, 2, 5, 6, Pfizer, 2, 5, 6, Roche, 1, 2, 5, 6; B. Terrier: AstraZeneca, 2, GlaxoSmithKline, 2, Novartis, 2, Vifor Pharma, 2; B. Hellmich: AbbVie, 2, 6, Amgen, 2, 6, AstraZeneca, 2, 6, Boehringer-Ingelheim, 2, 6, Bristol Myers Squibb, 2, 6, Chugai, 2, 6, GlaxoSmithKline, 2, 6, InflaRx, 2, 6, Janssen, 2, 6, MSD, 2, 6, Novartis, 2, 6, Pfizer, 2, 6, Phadia, 2, 6, Roche, 2, 6, Vifor Pharma, 2, 6; S. Necander: AstraZeneca, 3, 11; A. Shavit: AstraZeneca, 3, 11; C. Walton: AstraZeneca, 3, 11; M. Wechsler: Amgen, 2, AstraZeneca, 2, Boehringer-Ingelheim, 2, Cohero Health, 2, Equillium, 2, Genentech, 2, GlaxoSmithKline, 2, Novartis, 2, Regeneron Pharmaceuticals, 2, Sanofi–Genzyme, 2, Sentien Biotechnologies, 2, Teva, 2.