In the Journals

Checkpoint inhibitor induced inflammatory arthritis persists after discontinuation

Laura C. Cappelli

Inflammatory arthritis caused by immune checkpoint inhibitor therapy can develop into a long-term condition even after treatment cessation, requiring immunomodulatory intervention, according to findings published in Annals of the Rheumatic Diseases.

“This study was one of the first to evaluate persistence of immune-related adverse events beyond the cessation of immune checkpoint inhibitors,” Laura C. Cappelli, MD, MHS, MS, of the Johns Hopkins School of Medicine, told Healio Rheumatology. “It is important for physicians of all types to realize that these side effects may not be limited to when the patient is receiving immune checkpoint inhibitor therapy.”

To analyze the lasting outcomes of patients who develop inflammatory arthritis due to checkpoint therapy, and to define the factors linked to arthritis persistence after cessation and the need for immunosuppressants, Cappelli and colleagues conducted a prospective observational study of patients at the Johns Hopkins Arthritis Center. Participants included 60 adult patients who were referred to the center for rheumatologist-confirmed inflammatory arthritis due to checkpoint therapy for cancer, and recruited from June 2015 to December 2018. Participants were followed for a median of 9 months and an average of 12 months.

The researchers assessed participants at baseline and during follow-up visits at various intervals for up to 24 months following checkpoint therapy cessation. In addition, they used Kaplan-Meier curves to determine inflammatory arthritis persistence, as well as Cox proportional hazards models to analyze the impact of multiple factors on persistence. Cappelli and colleagues also evaluated the impact of arthritis treatment on tumor response.

Photo of cancer cell 
Inflammatory arthritis caused by immune checkpoint inhibitor therapy can develop into a long-term condition even after treatment cessation, requiring immunomodulatory intervention, according to findings.
Source: Adobe

According to the researchers, 53.3% of participants demonstrated active inflammatory arthritis at their most recent follow-up visit. Inflammatory arthritis was less likely to improve among patients with longer durations of checkpoint treatment, as well as in those who received combination checkpoint therapy and those with multiple other immune-related adverse events. Immunosuppression did not appear to impact tumor response.

“Those more likely to have persistent symptoms of inflammatory arthritis in our study were those who used checkpoint inhibitor longer, those with multiple other immune related adverse events, and those treated with combination immunotherapy,” Cappelli said. “These groups of patients would potentially benefit from early rheumatology referral and more aggressive upfront treatment of their arthritis.”

“Another important part of the study was looking at patients treated with DMARDs and those without, and whether there was a difference in tumor progression,” she added. “We did not see an increase in tumor progression in those treated with DMARDs — important information for rheumatologists trying to effectively treat patients without impacting their oncology outcomes.” – by Jason Laday

Disclosure: Cappelli reports consultant/advisory board membership with Regeneron/Sanofi, as well as grant funding from Bristol-Myers Squibb. Please see the full study for all other authors’ relevant financial disclosures.

Laura C. Cappelli

Inflammatory arthritis caused by immune checkpoint inhibitor therapy can develop into a long-term condition even after treatment cessation, requiring immunomodulatory intervention, according to findings published in Annals of the Rheumatic Diseases.

“This study was one of the first to evaluate persistence of immune-related adverse events beyond the cessation of immune checkpoint inhibitors,” Laura C. Cappelli, MD, MHS, MS, of the Johns Hopkins School of Medicine, told Healio Rheumatology. “It is important for physicians of all types to realize that these side effects may not be limited to when the patient is receiving immune checkpoint inhibitor therapy.”

To analyze the lasting outcomes of patients who develop inflammatory arthritis due to checkpoint therapy, and to define the factors linked to arthritis persistence after cessation and the need for immunosuppressants, Cappelli and colleagues conducted a prospective observational study of patients at the Johns Hopkins Arthritis Center. Participants included 60 adult patients who were referred to the center for rheumatologist-confirmed inflammatory arthritis due to checkpoint therapy for cancer, and recruited from June 2015 to December 2018. Participants were followed for a median of 9 months and an average of 12 months.

The researchers assessed participants at baseline and during follow-up visits at various intervals for up to 24 months following checkpoint therapy cessation. In addition, they used Kaplan-Meier curves to determine inflammatory arthritis persistence, as well as Cox proportional hazards models to analyze the impact of multiple factors on persistence. Cappelli and colleagues also evaluated the impact of arthritis treatment on tumor response.

Photo of cancer cell 
Inflammatory arthritis caused by immune checkpoint inhibitor therapy can develop into a long-term condition even after treatment cessation, requiring immunomodulatory intervention, according to findings.
Source: Adobe

According to the researchers, 53.3% of participants demonstrated active inflammatory arthritis at their most recent follow-up visit. Inflammatory arthritis was less likely to improve among patients with longer durations of checkpoint treatment, as well as in those who received combination checkpoint therapy and those with multiple other immune-related adverse events. Immunosuppression did not appear to impact tumor response.

“Those more likely to have persistent symptoms of inflammatory arthritis in our study were those who used checkpoint inhibitor longer, those with multiple other immune related adverse events, and those treated with combination immunotherapy,” Cappelli said. “These groups of patients would potentially benefit from early rheumatology referral and more aggressive upfront treatment of their arthritis.”

“Another important part of the study was looking at patients treated with DMARDs and those without, and whether there was a difference in tumor progression,” she added. “We did not see an increase in tumor progression in those treated with DMARDs — important information for rheumatologists trying to effectively treat patients without impacting their oncology outcomes.” – by Jason Laday

Disclosure: Cappelli reports consultant/advisory board membership with Regeneron/Sanofi, as well as grant funding from Bristol-Myers Squibb. Please see the full study for all other authors’ relevant financial disclosures.