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Dr. Jayatilleke scans the journals, so you don't have to!

Arundathi Jayatilleke, MD
The effects of glucocorticoids on bone health are well-recognized, with international rheumatology organizations recommending evaluation and treatment of glucocorticoid-induced osteoporosis in order to prevent fractures. Chronic use of glucocorticoids is known to take a toll early in the course of therapy; reductions in bone density can be seen even in the first several months. Whether these changes are seen even with use of low-dose glucocorticoids for RA is of interest. This retrospective cohort study from Abtahi et al. uses a large primary care database from the UK to examine the effects of current and past glucocorticoid exposure in over 15,000 people with RA, stratified as low (<7.5 mg/day), medium (7.5-15 mg/day) or high (>15 mg/day) doses. Low-dose glucocorticoid therapy was associated with an increased risk of vertebral fracture, though not at other sites, and current use did not increase risk compared to past use. Information on disease activity, which impacts glucocorticoid use and potentially effects on bone density, was not available in this study. With the widespread use of glucocorticoids in management of RA symptoms, this study highlights the importance of early identification of patients at risk for fracture and of vigilance even with use of low-dose glucocorticoids.

 

Herpes zoster infection is another well-known complication of RA and its treatment, including glucocorticoid therapy. An increased incidence has recently been noted in people who use JAK inhibitors, though other bDMARDs including TNF inhibitors are also known to increase risk. Redeker et al. compare the incidence of herpes zoster in people with RA using csDMARDs, bDMARDs, and tsDMARDs using a German prospective RA registry. In nearly 14,000 patients, 559 cases of herpes zoster were documented; after adjusting for age, sex, and glucocorticoid use, an increased risk was noted for treatment with monoclonal anti-TNF therapy, B-cell directed therapy, and JAK inhibitors compared to csDMARDs, whereas soluble TNF receptor fusion protein, T cell costimulation modulators and IL-6 inhibitors were not associated with a higher risk of herpes zoster compared with csDMARDs. Unfortunately, zoster vaccination status was not extracted for all patients. The study confirms what we already know with direct risk comparison between different agents and underscores the importance of vaccination in RA patients, especially those being treated with glucocorticoids and tsDMARDs.

 

Finally, another important consideration in the use of bDMARDs is the increase in cancer risk due to a potential reduction in immunosurveillance. Initial meta-analyses of clinical trials of anti-TNF agents highlighted an early increase in cancer risk, though later studies including meta-analyses and registry studies with longer follow-up durations have been equivocal. Huss et al. examine a Swedish registry of people with RA and no prior history of cancer and found a small increase in cancer-risk in patients with RA compared to the general population (HR 1.2). However, there was no increase in overall cancer incidence in patients treated with TNF inhibitors, rituximab, abatacept, or JAK inhibitors compared to RA patients naïve to bDMARDs and tsDMARDs. Interestingly, urinary tract cancer risk was slightly increased in several treatment groups, though the effect size was small. Considering the generally long duration of follow-up (with the exception of JAK inhibitors), this study is very reassuring regarding long-term risk of cancer of bDMARD use and useful in counseling people with RA on therapeutic risks.

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Arundathi Jayatilleke, MD
Lewis Katz School of Medicine, Temple University

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Arundathi Jayatilleke, MD
Lewis Katz School of Medicine, Temple University

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Arundathi Jayatilleke, MD
Lewis Katz School of Medicine, Temple University

Dr. Jayatilleke scans the journals, so you don't have to!
Dr. Jayatilleke scans the journals, so you don't have to!

Arundathi Jayatilleke, MD
The effects of glucocorticoids on bone health are well-recognized, with international rheumatology organizations recommending evaluation and treatment of glucocorticoid-induced osteoporosis in order to prevent fractures. Chronic use of glucocorticoids is known to take a toll early in the course of therapy; reductions in bone density can be seen even in the first several months. Whether these changes are seen even with use of low-dose glucocorticoids for RA is of interest. This retrospective cohort study from Abtahi et al. uses a large primary care database from the UK to examine the effects of current and past glucocorticoid exposure in over 15,000 people with RA, stratified as low (<7.5 mg/day), medium (7.5-15 mg/day) or high (>15 mg/day) doses. Low-dose glucocorticoid therapy was associated with an increased risk of vertebral fracture, though not at other sites, and current use did not increase risk compared to past use. Information on disease activity, which impacts glucocorticoid use and potentially effects on bone density, was not available in this study. With the widespread use of glucocorticoids in management of RA symptoms, this study highlights the importance of early identification of patients at risk for fracture and of vigilance even with use of low-dose glucocorticoids.

 

Herpes zoster infection is another well-known complication of RA and its treatment, including glucocorticoid therapy. An increased incidence has recently been noted in people who use JAK inhibitors, though other bDMARDs including TNF inhibitors are also known to increase risk. Redeker et al. compare the incidence of herpes zoster in people with RA using csDMARDs, bDMARDs, and tsDMARDs using a German prospective RA registry. In nearly 14,000 patients, 559 cases of herpes zoster were documented; after adjusting for age, sex, and glucocorticoid use, an increased risk was noted for treatment with monoclonal anti-TNF therapy, B-cell directed therapy, and JAK inhibitors compared to csDMARDs, whereas soluble TNF receptor fusion protein, T cell costimulation modulators and IL-6 inhibitors were not associated with a higher risk of herpes zoster compared with csDMARDs. Unfortunately, zoster vaccination status was not extracted for all patients. The study confirms what we already know with direct risk comparison between different agents and underscores the importance of vaccination in RA patients, especially those being treated with glucocorticoids and tsDMARDs.

 

Finally, another important consideration in the use of bDMARDs is the increase in cancer risk due to a potential reduction in immunosurveillance. Initial meta-analyses of clinical trials of anti-TNF agents highlighted an early increase in cancer risk, though later studies including meta-analyses and registry studies with longer follow-up durations have been equivocal. Huss et al. examine a Swedish registry of people with RA and no prior history of cancer and found a small increase in cancer-risk in patients with RA compared to the general population (HR 1.2). However, there was no increase in overall cancer incidence in patients treated with TNF inhibitors, rituximab, abatacept, or JAK inhibitors compared to RA patients naïve to bDMARDs and tsDMARDs. Interestingly, urinary tract cancer risk was slightly increased in several treatment groups, though the effect size was small. Considering the generally long duration of follow-up (with the exception of JAK inhibitors), this study is very reassuring regarding long-term risk of cancer of bDMARD use and useful in counseling people with RA on therapeutic risks.

Arundathi Jayatilleke, MD
The effects of glucocorticoids on bone health are well-recognized, with international rheumatology organizations recommending evaluation and treatment of glucocorticoid-induced osteoporosis in order to prevent fractures. Chronic use of glucocorticoids is known to take a toll early in the course of therapy; reductions in bone density can be seen even in the first several months. Whether these changes are seen even with use of low-dose glucocorticoids for RA is of interest. This retrospective cohort study from Abtahi et al. uses a large primary care database from the UK to examine the effects of current and past glucocorticoid exposure in over 15,000 people with RA, stratified as low (<7.5 mg/day), medium (7.5-15 mg/day) or high (>15 mg/day) doses. Low-dose glucocorticoid therapy was associated with an increased risk of vertebral fracture, though not at other sites, and current use did not increase risk compared to past use. Information on disease activity, which impacts glucocorticoid use and potentially effects on bone density, was not available in this study. With the widespread use of glucocorticoids in management of RA symptoms, this study highlights the importance of early identification of patients at risk for fracture and of vigilance even with use of low-dose glucocorticoids.

 

Herpes zoster infection is another well-known complication of RA and its treatment, including glucocorticoid therapy. An increased incidence has recently been noted in people who use JAK inhibitors, though other bDMARDs including TNF inhibitors are also known to increase risk. Redeker et al. compare the incidence of herpes zoster in people with RA using csDMARDs, bDMARDs, and tsDMARDs using a German prospective RA registry. In nearly 14,000 patients, 559 cases of herpes zoster were documented; after adjusting for age, sex, and glucocorticoid use, an increased risk was noted for treatment with monoclonal anti-TNF therapy, B-cell directed therapy, and JAK inhibitors compared to csDMARDs, whereas soluble TNF receptor fusion protein, T cell costimulation modulators and IL-6 inhibitors were not associated with a higher risk of herpes zoster compared with csDMARDs. Unfortunately, zoster vaccination status was not extracted for all patients. The study confirms what we already know with direct risk comparison between different agents and underscores the importance of vaccination in RA patients, especially those being treated with glucocorticoids and tsDMARDs.

 

Finally, another important consideration in the use of bDMARDs is the increase in cancer risk due to a potential reduction in immunosurveillance. Initial meta-analyses of clinical trials of anti-TNF agents highlighted an early increase in cancer risk, though later studies including meta-analyses and registry studies with longer follow-up durations have been equivocal. Huss et al. examine a Swedish registry of people with RA and no prior history of cancer and found a small increase in cancer-risk in patients with RA compared to the general population (HR 1.2). However, there was no increase in overall cancer incidence in patients treated with TNF inhibitors, rituximab, abatacept, or JAK inhibitors compared to RA patients naïve to bDMARDs and tsDMARDs. Interestingly, urinary tract cancer risk was slightly increased in several treatment groups, though the effect size was small. Considering the generally long duration of follow-up (with the exception of JAK inhibitors), this study is very reassuring regarding long-term risk of cancer of bDMARD use and useful in counseling people with RA on therapeutic risks.

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