Benefit of burosumab in adults with X-linked hypophosphataemia (XLH) is maintained with long-term treatment.

To report the impact of continued burosumab treatment on clinical laboratory tests of efficacy, patient-reported outcomes (PROs) and ambulatory function in adults with X-linked hypophosphataemia who continued from a 96-week phase 3 study into a 48-week open-label extension. Eligible participants from the phase 3 study continued on the burosumab regimen received at the end of the phase 3 study for a further 48 weeks (n=31). Some (not all) received compassionate burosumab treatment between the two studies (a period of 6-18 months). The primary efficacy outcome was fasting serum phosphate concentration; secondary outcomes were serum 1,25 dihydroxyvitamin D concentration, renal phosphate reabsorption, PROs and ambulatory function. Improvements in fasting serum phosphate, serum 1,25 dihydroxyvitamin D and renal phosphate reabsorption at 96 weeks were maintained through the 48-week extension. Improvements were also maintained in stiffness and physical function measured using the Western Ontario and McMaster Universities Osteoarthritis Index, pain and fatigue endpoints measuring using the Brief Pain Inventory short-form and Brief Pain Inventory, respectively, and in ambulatory function (6-Minute Walk Test).A post-hoc exploratory analysis exploring outcomes in participants who discontinued burosumab treatment between the studies (n=7) and those who received at least one dose (n=23) indicated that the benefits of burosumab on clinical laboratory tests of efficacy, PROs and ambulatory function may be lost when treatment is interrupted but recover over time when treatment is reinstated. Continued treatment with burosumab appears necessary for sustained clinical benefit. Phase 3: NCT02526160; open-label extension: NCT03920072.

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Déclaration de conflit d'intérêts

Competing interests: The following authors served as clinical investigators for one or more studies, including this trial, sponsored by Ultragenyx Pharmaceutical in partnership with Kyowa Kirin International: A-LL, JSW, KB, MC-S, MKJ, MLB, PK, RKC, RHL, SHR and SK. A-LL, RK and RHL have received honoraria from Kyowa Kirin International for serving as an advisory board member. A-LL, RKC and RK have also received honoraria from Kyowa Kirin International for delivering presentations, and A-LL has received support from Kyowa Kirin International for attending meetings. MKJ and RHL have received consulting fees and grants from Kyowa Kirin International outside of the submitted work. SHR has received clinical trial funding from Amgen, UCB and AstraZeneca. AJR and AW are employees of Kyowa Kirin International and WS is an employee of Kyowa Kirin Pharmaceutical Development. AN and MN are employees of Chilli Consultancy and have received consultancy fees from Kyowa Kirin International to support the data analysis and medical writing of this manuscript and for projects outside this submitted work.