In the Journals

Mavrilimumab well tolerated among patients with RA

Gerd R. Burmester

Mavrilimumab treatment for more than 3 years maintained response and was well-tolerated among patients with rheumatoid arthritis, with no increase in the prevalence of associated adverse effects, according to findings published in Arthritis and Rheumatology.

“Mavrilimumab is a human monoclonal antibody that blocks the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor alpha, acting as a competitive antagonist of GM-CSF signaling,” Gerd R. Burmester, MD, of the University Medicine Berlin, told Healio Rheumatology. “It has previously demonstrated efficacy and an acceptable safety profile in patients with RA in two phase 2 studies.”

To determine the sustained safety and efficacy of mavrilimumab over a long-term period, the researchers detailed the safety profile of patients with RA who participated in those phase-two trials — both of which were randomized, double-blind, multi-center studies — as well as an open-label extension study.

In one study, 326 patients with moderate-to-severe RA and inadequate responses to disease-modifying antirheumatic drugs received mavrilimumab doses of either 30, 100 or 150 mg, or placebo, every other week, plus methotrexate. In the other study, 138 patients with inadequate responses to anti-TNF agents, or disease-modifying antirheumatic drugs, received mavrilimumab 100 mg every other week, or 50-mg doses of golimumab every 4 weeks, plus methotrexate.

Of those who completed the trials, or had inadequate responses at week 12, a total of 397 entered the open-label extension study, in which patients received 100-mg doses of mavrilimumab every other week, plus methotrexate. By the end of the open-label extension study, 345 participants remained on their treatment. Across all three studies, 442 patients received mavrilimumab.

According to the researchers, long-term mavrilimumab treatment was well tolerated, with most adverse events described as either mild or moderate in severity. The researchers observed low incidences of neutropenia (0.9%; 0.45/100 patient years) and serious infections (3.17%; 1.56/100 patient years) in the overall mavrilimumab population, and no reports of monocytopenia. In addition, pulmonary deterioration was not evident with long-term mavrilimumab treatment in addition to standard of care. In addition, the researchers observed clinically meaningful, long-term efficacy in patients receiving mavrilimumab for up to more than 3 years across many disease activity parameters.

“Biomarker analyses demonstrated sustained suppression of two GM-CSF pathway-related protein markers following mavrilimumab treatment, regardless of previous treatment received,” Burmester said. “These results support data from previous studies, confirming that CCL17/TARC and CCL22/MDC specifically relate to the GM-CSF pathway and indicating a potential benefit of inhibiting this pathway in RA treatment.” – by Jason Laday

Disclosure: The researchers report funding from MedImmune. Burmester reports research funding from UCB, Pfizer and Roche, as well as consulting and lecture fees from AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, MedImmune, Novartis, Pfizer and Roche. See the full study for additional researchers’ disclosures.

Gerd R. Burmester

Mavrilimumab treatment for more than 3 years maintained response and was well-tolerated among patients with rheumatoid arthritis, with no increase in the prevalence of associated adverse effects, according to findings published in Arthritis and Rheumatology.

“Mavrilimumab is a human monoclonal antibody that blocks the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor alpha, acting as a competitive antagonist of GM-CSF signaling,” Gerd R. Burmester, MD, of the University Medicine Berlin, told Healio Rheumatology. “It has previously demonstrated efficacy and an acceptable safety profile in patients with RA in two phase 2 studies.”

To determine the sustained safety and efficacy of mavrilimumab over a long-term period, the researchers detailed the safety profile of patients with RA who participated in those phase-two trials — both of which were randomized, double-blind, multi-center studies — as well as an open-label extension study.

In one study, 326 patients with moderate-to-severe RA and inadequate responses to disease-modifying antirheumatic drugs received mavrilimumab doses of either 30, 100 or 150 mg, or placebo, every other week, plus methotrexate. In the other study, 138 patients with inadequate responses to anti-TNF agents, or disease-modifying antirheumatic drugs, received mavrilimumab 100 mg every other week, or 50-mg doses of golimumab every 4 weeks, plus methotrexate.

Of those who completed the trials, or had inadequate responses at week 12, a total of 397 entered the open-label extension study, in which patients received 100-mg doses of mavrilimumab every other week, plus methotrexate. By the end of the open-label extension study, 345 participants remained on their treatment. Across all three studies, 442 patients received mavrilimumab.

According to the researchers, long-term mavrilimumab treatment was well tolerated, with most adverse events described as either mild or moderate in severity. The researchers observed low incidences of neutropenia (0.9%; 0.45/100 patient years) and serious infections (3.17%; 1.56/100 patient years) in the overall mavrilimumab population, and no reports of monocytopenia. In addition, pulmonary deterioration was not evident with long-term mavrilimumab treatment in addition to standard of care. In addition, the researchers observed clinically meaningful, long-term efficacy in patients receiving mavrilimumab for up to more than 3 years across many disease activity parameters.

“Biomarker analyses demonstrated sustained suppression of two GM-CSF pathway-related protein markers following mavrilimumab treatment, regardless of previous treatment received,” Burmester said. “These results support data from previous studies, confirming that CCL17/TARC and CCL22/MDC specifically relate to the GM-CSF pathway and indicating a potential benefit of inhibiting this pathway in RA treatment.” – by Jason Laday

Disclosure: The researchers report funding from MedImmune. Burmester reports research funding from UCB, Pfizer and Roche, as well as consulting and lecture fees from AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, MedImmune, Novartis, Pfizer and Roche. See the full study for additional researchers’ disclosures.