Mast cell synovitis: potential target in RA?

 

MAUI, HAWAII – Could mast cell-rich synovitis become a novel target in patients with early rheumatoid arthritis?

Investigators at the University of London believe so. In a small but provocative study presented at the 2017 annual meeting of the American College of Rheumatology, they demonstrated that these mast cells are not an innocent bystander in joint inflammation; rather, they play an active albeit still incompletely understood role in the synovial inflammatory infiltrate and in disease progression, Orrin M. Troum, MD, said at the 2018 Rheumatology Winter Clinical Symposium.

Bruce Jancin/Frontline Medical News

The proof-of-concept study, conducted as part of the Pathobiology of Early Arthritis Cohort at Barts Health NHS Trust, included 20 patients with RA of less than 12 months duration who had not received disease-modifying antirheumatic drug (DMARD) treatment. Investigators performed ultrasound-guided synovial tissue biopsies at baseline and after 6 months of treatment with methotrexate or other synthetic DMARDs. At baseline, higher synovial mast cell counts were strongly associated with higher synovial inflammation scores, the presence of lymphoid aggregates, and higher 28-joint Disease Activity Score (DAS28) levels.

Treatment with synthetic DMARDs was partially effective, both clinically and at the cellular level. Mean mast cell density fell from 14.2/mm² at baseline to 8.2/mm² at 6 months. But synovial mast cells were still present at 6 months in 9 of 20 patients. Those nine patients had significantly higher DAS28 scores – a mean of 4.08 versus 2.41 in the synovial mast cell–negative group – as well as higher synovitis scores. Disease remission as defined by a DAS28 score below 2.6 was achieved in only 2 of 9 patients with persistent mast cell-rich synovitis, as compared with 8 of 11 mast cell-negative patients.

 

Moreover, four of the nine patients with persistent mast cell-rich synovitis after 6 months of synthetic DMARDs had synovial lymphoid aggregates of CD20-positive B cells and/or CD138-positive plasma cells; in contrast, none of the 11 synovial mast cell-negative patients did, noted Dr. Troum, a rheumatologist at the University of Southern California, Los Angeles, who is in private practice in Santa Monica, Calif.

In theory, if a baseline synovial tissue immune cell profile could be identified that’s predictive of high-level responsiveness to synthetic DMARDs or, conversely, nonresponsiveness, tissue specimens could be used to stratify patients with early RA to different initial treatment strategies. The problem with that is few rheumatologists in the United States – and indeed worldwide – are proficient at performing ultrasound-guided synovial biopsies, according to Dr. Troum.

His description of the London study prompted a question as to whether any of the biologics used in rheumatology can inhibit mast cells. Arthur Kavanaugh, MD, symposium director, said the only agent that comes to mind is imatinib (Gleevec), a tyrosine kinase inhibitor used in the treatment of aggressive systemic mastocytosis as well as for certain leukemias.

“It has a ton of toxicity, though,” said Dr. Kavanaugh, professor of medicine and director of the Center for Innovative Therapy in the division of rheumatology, allergy, and immunology at the University of California, San Diego.

Dr. Troum reported having no financial conflicts regarding his presentation.

bjancin@frontlinemedcom.com

 

MAUI, HAWAII – Could mast cell-rich synovitis become a novel target in patients with early rheumatoid arthritis?

Investigators at the University of London believe so. In a small but provocative study presented at the 2017 annual meeting of the American College of Rheumatology, they demonstrated that these mast cells are not an innocent bystander in joint inflammation; rather, they play an active albeit still incompletely understood role in the synovial inflammatory infiltrate and in disease progression, Orrin M. Troum, MD, said at the 2018 Rheumatology Winter Clinical Symposium.

Bruce Jancin/Frontline Medical News

The proof-of-concept study, conducted as part of the Pathobiology of Early Arthritis Cohort at Barts Health NHS Trust, included 20 patients with RA of less than 12 months duration who had not received disease-modifying antirheumatic drug (DMARD) treatment. Investigators performed ultrasound-guided synovial tissue biopsies at baseline and after 6 months of treatment with methotrexate or other synthetic DMARDs. At baseline, higher synovial mast cell counts were strongly associated with higher synovial inflammation scores, the presence of lymphoid aggregates, and higher 28-joint Disease Activity Score (DAS28) levels.

Treatment with synthetic DMARDs was partially effective, both clinically and at the cellular level. Mean mast cell density fell from 14.2/mm² at baseline to 8.2/mm² at 6 months. But synovial mast cells were still present at 6 months in 9 of 20 patients. Those nine patients had significantly higher DAS28 scores – a mean of 4.08 versus 2.41 in the synovial mast cell–negative group – as well as higher synovitis scores. Disease remission as defined by a DAS28 score below 2.6 was achieved in only 2 of 9 patients with persistent mast cell-rich synovitis, as compared with 8 of 11 mast cell-negative patients.

 

Moreover, four of the nine patients with persistent mast cell-rich synovitis after 6 months of synthetic DMARDs had synovial lymphoid aggregates of CD20-positive B cells and/or CD138-positive plasma cells; in contrast, none of the 11 synovial mast cell-negative patients did, noted Dr. Troum, a rheumatologist at the University of Southern California, Los Angeles, who is in private practice in Santa Monica, Calif.

In theory, if a baseline synovial tissue immune cell profile could be identified that’s predictive of high-level responsiveness to synthetic DMARDs or, conversely, nonresponsiveness, tissue specimens could be used to stratify patients with early RA to different initial treatment strategies. The problem with that is few rheumatologists in the United States – and indeed worldwide – are proficient at performing ultrasound-guided synovial biopsies, according to Dr. Troum.

His description of the London study prompted a question as to whether any of the biologics used in rheumatology can inhibit mast cells. Arthur Kavanaugh, MD, symposium director, said the only agent that comes to mind is imatinib (Gleevec), a tyrosine kinase inhibitor used in the treatment of aggressive systemic mastocytosis as well as for certain leukemias.

“It has a ton of toxicity, though,” said Dr. Kavanaugh, professor of medicine and director of the Center for Innovative Therapy in the division of rheumatology, allergy, and immunology at the University of California, San Diego.

Dr. Troum reported having no financial conflicts regarding his presentation.

bjancin@frontlinemedcom.com

 

MAUI, HAWAII – Could mast cell-rich synovitis become a novel target in patients with early rheumatoid arthritis?

Investigators at the University of London believe so. In a small but provocative study presented at the 2017 annual meeting of the American College of Rheumatology, they demonstrated that these mast cells are not an innocent bystander in joint inflammation; rather, they play an active albeit still incompletely understood role in the synovial inflammatory infiltrate and in disease progression, Orrin M. Troum, MD, said at the 2018 Rheumatology Winter Clinical Symposium.

Bruce Jancin/Frontline Medical News

The proof-of-concept study, conducted as part of the Pathobiology of Early Arthritis Cohort at Barts Health NHS Trust, included 20 patients with RA of less than 12 months duration who had not received disease-modifying antirheumatic drug (DMARD) treatment. Investigators performed ultrasound-guided synovial tissue biopsies at baseline and after 6 months of treatment with methotrexate or other synthetic DMARDs. At baseline, higher synovial mast cell counts were strongly associated with higher synovial inflammation scores, the presence of lymphoid aggregates, and higher 28-joint Disease Activity Score (DAS28) levels.

Treatment with synthetic DMARDs was partially effective, both clinically and at the cellular level. Mean mast cell density fell from 14.2/mm² at baseline to 8.2/mm² at 6 months. But synovial mast cells were still present at 6 months in 9 of 20 patients. Those nine patients had significantly higher DAS28 scores – a mean of 4.08 versus 2.41 in the synovial mast cell–negative group – as well as higher synovitis scores. Disease remission as defined by a DAS28 score below 2.6 was achieved in only 2 of 9 patients with persistent mast cell-rich synovitis, as compared with 8 of 11 mast cell-negative patients.

 

Moreover, four of the nine patients with persistent mast cell-rich synovitis after 6 months of synthetic DMARDs had synovial lymphoid aggregates of CD20-positive B cells and/or CD138-positive plasma cells; in contrast, none of the 11 synovial mast cell-negative patients did, noted Dr. Troum, a rheumatologist at the University of Southern California, Los Angeles, who is in private practice in Santa Monica, Calif.

In theory, if a baseline synovial tissue immune cell profile could be identified that’s predictive of high-level responsiveness to synthetic DMARDs or, conversely, nonresponsiveness, tissue specimens could be used to stratify patients with early RA to different initial treatment strategies. The problem with that is few rheumatologists in the United States – and indeed worldwide – are proficient at performing ultrasound-guided synovial biopsies, according to Dr. Troum.

His description of the London study prompted a question as to whether any of the biologics used in rheumatology can inhibit mast cells. Arthur Kavanaugh, MD, symposium director, said the only agent that comes to mind is imatinib (Gleevec), a tyrosine kinase inhibitor used in the treatment of aggressive systemic mastocytosis as well as for certain leukemias.

“It has a ton of toxicity, though,” said Dr. Kavanaugh, professor of medicine and director of the Center for Innovative Therapy in the division of rheumatology, allergy, and immunology at the University of California, San Diego.

Dr. Troum reported having no financial conflicts regarding his presentation.

bjancin@frontlinemedcom.com