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Published on: December 26, 2017
Efficacy and safety of emapalumab in macrophage activation syndrome
Fabrizio De Benedetti1, Alexei A Grom2,3, Paul A Brogan4
1Division of Rheumatology, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy fabrizio.debenedetti@opbg.net.
Objectives:
Macrophage activation syndrome (MAS) is a severe, life-threatening complication of systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD). The objective of this study was to confirm the adequacy of an emapalumab dosing regimen in relation to interferon-γ (IFNγ) activity by assessing efficacy and safety. The efficacy outcome was MAS remission by week 8, based on clinical and laboratory criteria.
Methods:
We studied emapalumab, a human anti-IFNγ antibody, administered with background glucocorticoids, in a prospective single-arm trial involving patients who had MAS secondary to sJIA or AOSD and had previously failed high-dose glucocorticoids, with or without anakinra and/or ciclosporin. The study foresaw 4-week treatment that could be shortened or prolonged based on investigator's assessment of response. Patients entered a long-term (12 months) follow-up study.
Results:
Fourteen patients received emapalumab. All patients completed the trial, entered the long-term follow-up and were alive at the end of follow-up. The investigated dosing regimen, based on an initial loading dose followed by maintenance doses, was appropriate, as shown by rapid neutralisation of IFNγ activity, demonstrated by a prompt decrease in serum C-X-C motif chemokine ligand 9 (CXCL9) levels. By week 8, MAS remission was achieved in 13 of the 14 patients at a median time of 25 days. Viral infections and positive viral tests were observed.
Conclusions:
Neutralisation of IFNγ with emapalumab was efficacious in inducing remission of MAS secondary to sJIA or AOSD in patients who had failed high-dose glucocorticoids. Screening for viral infections should be performed, particularly for cytomegalovirus.
Trial Registration Number:
NCT02069899 and NCT03311854.
Insights
Emapalumab effectively treats macrophage activation syndrome (MAS) in patients with systemic juvenile idiopathic arthritis (sJIA) or adult-onset Still
Area of Science:
- Rheumatology
- Immunology
- Clinical Pharmacology
Background:
- Macrophage activation syndrome (MAS) is a severe complication of systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD).
- Interferon-gamma (IFNγ) plays a critical role in MAS pathogenesis.
- Existing treatments, including high-dose glucocorticoids, often prove insufficient.
Purpose of the Study:
- To evaluate the efficacy and safety of emapalumab, an anti-IFNγ antibody, in treating MAS.
- To confirm the adequacy of the emapalumab dosing regimen by assessing its impact on IFNγ activity.
- To achieve MAS remission by week 8.
Main Methods:
- A prospective, single-arm trial involving 14 patients with MAS secondary to sJIA or AOSD.
- Patients had previously failed glucocorticoid therapy, with or without other immunosuppressants.
- Emapalumab was administered with background glucocorticoids, with treatment duration adjusted based on response.
Main Results:
- The emapalumab dosing regimen was appropriate, evidenced by rapid IFNγ neutralization and decreased CXCL9 levels.
- MAS remission was achieved in 13 out of 14 patients by week 8 (median time 25 days).
- Viral infections and positive viral tests were observed during the study.
Conclusions:
- Emapalumab is efficacious in inducing MAS remission in patients refractory to high-dose glucocorticoids.
- Neutralization of IFNγ with emapalumab provides a targeted therapeutic approach for MAS.
- Screening for viral infections, especially cytomegalovirus, is recommended.
