Novel Anti-GM-CSFR Monoclonal Antibody Shows Promise in RA

CHICAGO – Mavrilimumab has shown promise for the treatment of rheumatoid arthritis in a randomized, placebo-controlled, phase II study.

The agent is a novel human monoclonal antibody that targets granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR) alpha, which has been implicated in the rheumatoid arthritis (RA) disease process by findings from prior preclinical and animal studies.

During the 12-week, dose-ranging study, 55.7% of 149 patients who were randomized to receive 10, 30, 50, or 100 mg of active treatment achieved the primary end point of at least a 1.2-point reduction in the Disease Activity Score 28 as measured using C-reactive protein (DAS28-CRP), compared with only 34.7% of 67 patients randomized to receive placebo. The difference was statistically significant, Dr. Gerd R. Burmester reported at the annual meeting of the American College of Rheumatology.

Response generally occurred within 2 weeks of treatment initiation, and the most significant improvement was seen in patients who were randomized to receive 100 mg of mavrilimumab, with 66.7%, of patients in the 100-mg group achieving the primary end point, compared with 41.0%, 61.0%, and 53.8% of those in the 10-, 30-, and 50-mg groups, respectively, said Dr. Burmester, professor of medicine in the department of rheumatology and clinical immunology at Charité Universitätsmedizin Berlin.

Patients receiving active treatment also were more likely than those receiving placebo to achieve DAS28-CRP remission, with significantly higher remission rates seen both overall (18.4%) and in the 100-mg group (23.1%), compared with placebo (6.7%). ACR 20, 50, and 70 responses (American College of Rheumatology assessment scales based on 20%, 50%, and 70% improvement in specified parameters) were also better in the mavrilimumab patients, compared with the placebo patients, with significantly better improvement seen between the 100-mg group and the placebo group for all three ACR response categories, as well as overall and in the 30-mg group, compared with placebo, for the ACR 50 response category.

Mavrilimumab patients also were more likely to achieve a 0.25-point improvement in HAQ-DI (Health Assessment Questionnaire–Disability Index) scores, compared with placebo patients, with significant differences in the response rates occurring both overall (63.3%) and in the 100-mg group (74.4%), compared with placebo (48.0%), Dr. Burmester said.

Treatment in this study was well tolerated.

"Basically, there were very, very few safety signals at all," he said, noting that serious adverse events were reported in 1.3% and 1.9% of mavrilimumab and placebo patients, respectively, and that none of those events was treatment related.

Other adverse events included a decrease in carbon monoxide diffusing capacity and nasopharyngitis, which each occurred more often in the mavrilimumab patients vs. the placebo patients (11.9% vs. 5.1%, and 6.3% vs. 2.5%, respectively), and upper respiratory infections, which occurred more often in the placebo patients (3.8% vs. 5.1%). These events were generally mild or moderate in intensity.

No significant hypersensitivity reactions, anaphylaxis, opportunistic infections, or pulmonary parameters were reported, Dr. Burmester said.

Study participants were adults from Eastern Europe who had active adult-onset RA of at least 3 months’ duration, and who were positive for anti–cyclic citrullinated protein antibody and/or rheumatoid factor. They had a DAS28-CRP of at least 3.2 at baseline.

"We believe the results from this study suggest that suppressing macrophage activity and targeting the GM-CSF receptor may be a novel approach to the treatment of rheumatoid arthritis," Dr. Burmester said, concluding that the rapid and significant clinical effects seen in the study, as well as the acceptable short-term safety profile, support further clinical development of mavrilimumab.

Dr. Burmester disclosed that he has received consulting fees or other remuneration from Medimmune Ltd., the maker of mavrilimumab. Several other authors on this study also disclosed financial relationships with Medimmune and/or AstraZeneca.

CHICAGO – Mavrilimumab has shown promise for the treatment of rheumatoid arthritis in a randomized, placebo-controlled, phase II study.

The agent is a novel human monoclonal antibody that targets granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR) alpha, which has been implicated in the rheumatoid arthritis (RA) disease process by findings from prior preclinical and animal studies.

During the 12-week, dose-ranging study, 55.7% of 149 patients who were randomized to receive 10, 30, 50, or 100 mg of active treatment achieved the primary end point of at least a 1.2-point reduction in the Disease Activity Score 28 as measured using C-reactive protein (DAS28-CRP), compared with only 34.7% of 67 patients randomized to receive placebo. The difference was statistically significant, Dr. Gerd R. Burmester reported at the annual meeting of the American College of Rheumatology.

Response generally occurred within 2 weeks of treatment initiation, and the most significant improvement was seen in patients who were randomized to receive 100 mg of mavrilimumab, with 66.7%, of patients in the 100-mg group achieving the primary end point, compared with 41.0%, 61.0%, and 53.8% of those in the 10-, 30-, and 50-mg groups, respectively, said Dr. Burmester, professor of medicine in the department of rheumatology and clinical immunology at Charité Universitätsmedizin Berlin.

Patients receiving active treatment also were more likely than those receiving placebo to achieve DAS28-CRP remission, with significantly higher remission rates seen both overall (18.4%) and in the 100-mg group (23.1%), compared with placebo (6.7%). ACR 20, 50, and 70 responses (American College of Rheumatology assessment scales based on 20%, 50%, and 70% improvement in specified parameters) were also better in the mavrilimumab patients, compared with the placebo patients, with significantly better improvement seen between the 100-mg group and the placebo group for all three ACR response categories, as well as overall and in the 30-mg group, compared with placebo, for the ACR 50 response category.

Mavrilimumab patients also were more likely to achieve a 0.25-point improvement in HAQ-DI (Health Assessment Questionnaire–Disability Index) scores, compared with placebo patients, with significant differences in the response rates occurring both overall (63.3%) and in the 100-mg group (74.4%), compared with placebo (48.0%), Dr. Burmester said.

Treatment in this study was well tolerated.

"Basically, there were very, very few safety signals at all," he said, noting that serious adverse events were reported in 1.3% and 1.9% of mavrilimumab and placebo patients, respectively, and that none of those events was treatment related.

Other adverse events included a decrease in carbon monoxide diffusing capacity and nasopharyngitis, which each occurred more often in the mavrilimumab patients vs. the placebo patients (11.9% vs. 5.1%, and 6.3% vs. 2.5%, respectively), and upper respiratory infections, which occurred more often in the placebo patients (3.8% vs. 5.1%). These events were generally mild or moderate in intensity.

No significant hypersensitivity reactions, anaphylaxis, opportunistic infections, or pulmonary parameters were reported, Dr. Burmester said.

Study participants were adults from Eastern Europe who had active adult-onset RA of at least 3 months’ duration, and who were positive for anti–cyclic citrullinated protein antibody and/or rheumatoid factor. They had a DAS28-CRP of at least 3.2 at baseline.

"We believe the results from this study suggest that suppressing macrophage activity and targeting the GM-CSF receptor may be a novel approach to the treatment of rheumatoid arthritis," Dr. Burmester said, concluding that the rapid and significant clinical effects seen in the study, as well as the acceptable short-term safety profile, support further clinical development of mavrilimumab.

Dr. Burmester disclosed that he has received consulting fees or other remuneration from Medimmune Ltd., the maker of mavrilimumab. Several other authors on this study also disclosed financial relationships with Medimmune and/or AstraZeneca.

CHICAGO – Mavrilimumab has shown promise for the treatment of rheumatoid arthritis in a randomized, placebo-controlled, phase II study.

The agent is a novel human monoclonal antibody that targets granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR) alpha, which has been implicated in the rheumatoid arthritis (RA) disease process by findings from prior preclinical and animal studies.

During the 12-week, dose-ranging study, 55.7% of 149 patients who were randomized to receive 10, 30, 50, or 100 mg of active treatment achieved the primary end point of at least a 1.2-point reduction in the Disease Activity Score 28 as measured using C-reactive protein (DAS28-CRP), compared with only 34.7% of 67 patients randomized to receive placebo. The difference was statistically significant, Dr. Gerd R. Burmester reported at the annual meeting of the American College of Rheumatology.

Response generally occurred within 2 weeks of treatment initiation, and the most significant improvement was seen in patients who were randomized to receive 100 mg of mavrilimumab, with 66.7%, of patients in the 100-mg group achieving the primary end point, compared with 41.0%, 61.0%, and 53.8% of those in the 10-, 30-, and 50-mg groups, respectively, said Dr. Burmester, professor of medicine in the department of rheumatology and clinical immunology at Charité Universitätsmedizin Berlin.

Patients receiving active treatment also were more likely than those receiving placebo to achieve DAS28-CRP remission, with significantly higher remission rates seen both overall (18.4%) and in the 100-mg group (23.1%), compared with placebo (6.7%). ACR 20, 50, and 70 responses (American College of Rheumatology assessment scales based on 20%, 50%, and 70% improvement in specified parameters) were also better in the mavrilimumab patients, compared with the placebo patients, with significantly better improvement seen between the 100-mg group and the placebo group for all three ACR response categories, as well as overall and in the 30-mg group, compared with placebo, for the ACR 50 response category.

Mavrilimumab patients also were more likely to achieve a 0.25-point improvement in HAQ-DI (Health Assessment Questionnaire–Disability Index) scores, compared with placebo patients, with significant differences in the response rates occurring both overall (63.3%) and in the 100-mg group (74.4%), compared with placebo (48.0%), Dr. Burmester said.

Treatment in this study was well tolerated.

"Basically, there were very, very few safety signals at all," he said, noting that serious adverse events were reported in 1.3% and 1.9% of mavrilimumab and placebo patients, respectively, and that none of those events was treatment related.

Other adverse events included a decrease in carbon monoxide diffusing capacity and nasopharyngitis, which each occurred more often in the mavrilimumab patients vs. the placebo patients (11.9% vs. 5.1%, and 6.3% vs. 2.5%, respectively), and upper respiratory infections, which occurred more often in the placebo patients (3.8% vs. 5.1%). These events were generally mild or moderate in intensity.

No significant hypersensitivity reactions, anaphylaxis, opportunistic infections, or pulmonary parameters were reported, Dr. Burmester said.

Study participants were adults from Eastern Europe who had active adult-onset RA of at least 3 months’ duration, and who were positive for anti–cyclic citrullinated protein antibody and/or rheumatoid factor. They had a DAS28-CRP of at least 3.2 at baseline.

"We believe the results from this study suggest that suppressing macrophage activity and targeting the GM-CSF receptor may be a novel approach to the treatment of rheumatoid arthritis," Dr. Burmester said, concluding that the rapid and significant clinical effects seen in the study, as well as the acceptable short-term safety profile, support further clinical development of mavrilimumab.

Dr. Burmester disclosed that he has received consulting fees or other remuneration from Medimmune Ltd., the maker of mavrilimumab. Several other authors on this study also disclosed financial relationships with Medimmune and/or AstraZeneca.