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Mavrilimumab, a Fully Human Granulocyte–Macrophage Colony‐Stimulating Factor Receptor α Monoclonal Antibody
Author(s) -
Burmester Gerd R.,
McInnes Iain B.,
Kremer Joel M.,
Miranda Pedro,
Vencovský Jiří,
Godwood Alex,
Albulescu Marius,
Michaels M. Alex,
Guo Xiang,
Close David,
Weinblatt Michael
Publication year - 2018
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.40420
Subject(s) - medicine , adverse effect , rheumatoid arthritis , gastroenterology , surgery
Objective Mavrilimumab, a human monoclonal antibody, targets granulocyte–macrophage colony‐stimulating factor receptor α. We undertook to determine the long‐term safety and efficacy of mavrilimumab in rheumatoid arthritis patients in 2 phase II b studies (1071 and 1107) and in 1 open‐label extension study (ClinicalTrials.gov identifier: NCT 01712399). Methods In study 1071, patients with an inadequate response to disease‐modifying antirheumatic drugs ( DMARD s) received mavrilimumab (30, 100, or 150 mg) or placebo every other week plus methotrexate. In study 1107, patients with an inadequate response to anti–tumor necrosis factor agents and/or DMARD s received 100 mg mavrilimumab every other week or 50 mg golimumab every 4 weeks plus methotrexate. Patients entering the open‐label extension study received 100 mg mavrilimumab every other week plus methotrexate. Long‐term safety and efficacy of mavrilimumab were assessed. Results A total of 442 patients received mavrilimumab (14 of 245 patients from study 1071, 9 of 70 patients from study 1107, and 52 of 397 patients from the open‐label extension study discontinued mavrilimumab treatment throughout the studies). The cumulative safety exposure was 899 patient‐years; the median duration of mavrilimumab treatment was 2.5 years (range 0.1–3.3 years). The most common treatment‐emergent adverse events ( AE s) were nasopharyngitis (n = 69; 7.68 per 100 patient‐years) and bronchitis (n = 51; 5.68 per 100 patient‐years). At weeks 74 and 104, 3.5% and 6.2% of patients, respectively, demonstrated reduction in forced expiratory volume in 1 second, while 2.9% and 3.4% of patients, respectively, demonstrated reduction in forced vital capacity (>20% reduction from baseline to <80% predicted). Most pulmonary changes were transient and only infrequently associated with AE s. Mavrilimumab at 100 mg every other week demonstrated sustained efficacy; at week 122, 65.0% of patients achieved a Disease Activity Score in 28 joints using the C‐reactive protein level ( DAS 28‐ CRP ) of <3.2, and 40.6% of patients achieved a DAS 28‐ CRP of <2.6. Conclusion Long‐term treatment with mavrilimumab maintained response and was well‐tolerated with no increased incidence of treatment‐emergent AE s. Safety data were comparable with those from both phase II b qualifying studies.