Clinical Edge Journal Scan Commentary: RA January 2022

Along with long-standing concerns about immunodeficiency and use of immunosuppressive medication in people with rheumatoid arthritis (RA) are juxtaposed concerns about their additional risk of COVID-19 during the pandemic. Several studies have reported a high risk of severe COVID-19 outcomes in people with rheumatic disease, though few have compared this risk to the general population. This cohort study by Wang et al.¹ examines the risk of COVID-19 in people with RA compared to people with OA and the general population based on an electronic medical record database in the UK. The rate of COVID-19 was higher among people with RA than the general population, with a hazard ratio of 1.42 for confirmed COVID-19 cases, while the rate among people with OA was not increased. This finding confirms suspicions, though, due to the study design, it does not lend additional insight into nuances given the lack of information about RA treatment and activity as in prior studies.

Also of concern in the midst of the pandemic is the effect of RA and its treatment on response to vaccines against SARS-CoV-2. The rapid development of mRNA vaccines has been a boon, but research on vaccine response in people with rheumatic disease has suggested that certain medications can impact antibody formation. Iancovici et al.² examined antibody and B cell responses after vaccination in people with RA being treated with Janus kinase (JAK)-inhibitors or tumor necrosis factor (TNF)-inhibitors and in healthy volunteers. Though the study is flawed as responses were not assessed at the same timepoint after vaccination in all subjects and limited due to the heterogeneity of treatment and small numbers of subjects, antibody production and other assays were decreased in RA subjects, suggesting reduced humoral immunity. Whether a pause in JAK inhibitor treatment, as recommended by the American College of Rheumatology, makes an appreciable difference in these assessments of vaccine response is as yet unknown. Further, given the limited data, it is unclear whether having RA on its own, rather than the treatments involved, was the causative factor. Research is already underway on SARS-CoV-2 vaccine response in people with RA and other rheumatic diseases, but studies such as these also imply a relative immunodeficiency due to the diseases and their treatment that could extend to other vaccines or infections.

In addition to impacts on SARS-CoV-2 vaccine response, treatment with JAK inhibitors is known to increase risk of herpes zoster (HZ). A post hoc analysis of pooled data from 21 RA and 3 psoriatic arthritis (PsA) tofacitinib trials by Winthrop et al.³ evaluated the number and severity of HZ infections. Interestingly, HZ infections occurred more frequently in participants in the RA clinical trials, with about 11% having an infection compared to 5% in the PsA studies, once again highlighting a potential immunodeficiency particular to people with RA. Most patients had mild to moderate infections, but a small proportion of patients (<5%) had severe infections. Given the possibility of a reduced vaccine response, though unknown, after HZ vaccination in people with RA, consideration should be given not only to vaccination prior to initiation of JAK inhibitor therapy, but to assessment of vaccine efficacy and the ideal dosing schedules in these patients.

References

1. Wang Y et al. Increased risk of COVID-19 in patients with rheumatoid arthritis: a general population-based cohort study. Arthritis Care Res (Hoboken) 2021(Dec 7). 
2. Iancovici L et al. Rheumatoid arthritis patients treated with Janus kinase inhibitors show reduced humoral immune responses following BNT162b2 vaccination. Rheumatology (Oxford). 2021:keab879 (Nov 25).
3. Winthrop KL et al. Clinical management of herpes zoster in patients with rheumatoid arthritis or psoriatic arthritis receiving tofacitinib treatment. Rheumatol Ther. 2021 (Dec 6).

Along with long-standing concerns about immunodeficiency and use of immunosuppressive medication in people with rheumatoid arthritis (RA) are juxtaposed concerns about their additional risk of COVID-19 during the pandemic. Several studies have reported a high risk of severe COVID-19 outcomes in people with rheumatic disease, though few have compared this risk to the general population. This cohort study by Wang et al.¹ examines the risk of COVID-19 in people with RA compared to people with OA and the general population based on an electronic medical record database in the UK. The rate of COVID-19 was higher among people with RA than the general population, with a hazard ratio of 1.42 for confirmed COVID-19 cases, while the rate among people with OA was not increased. This finding confirms suspicions, though, due to the study design, it does not lend additional insight into nuances given the lack of information about RA treatment and activity as in prior studies.

Also of concern in the midst of the pandemic is the effect of RA and its treatment on response to vaccines against SARS-CoV-2. The rapid development of mRNA vaccines has been a boon, but research on vaccine response in people with rheumatic disease has suggested that certain medications can impact antibody formation. Iancovici et al.² examined antibody and B cell responses after vaccination in people with RA being treated with Janus kinase (JAK)-inhibitors or tumor necrosis factor (TNF)-inhibitors and in healthy volunteers. Though the study is flawed as responses were not assessed at the same timepoint after vaccination in all subjects and limited due to the heterogeneity of treatment and small numbers of subjects, antibody production and other assays were decreased in RA subjects, suggesting reduced humoral immunity. Whether a pause in JAK inhibitor treatment, as recommended by the American College of Rheumatology, makes an appreciable difference in these assessments of vaccine response is as yet unknown. Further, given the limited data, it is unclear whether having RA on its own, rather than the treatments involved, was the causative factor. Research is already underway on SARS-CoV-2 vaccine response in people with RA and other rheumatic diseases, but studies such as these also imply a relative immunodeficiency due to the diseases and their treatment that could extend to other vaccines or infections.

In addition to impacts on SARS-CoV-2 vaccine response, treatment with JAK inhibitors is known to increase risk of herpes zoster (HZ). A post hoc analysis of pooled data from 21 RA and 3 psoriatic arthritis (PsA) tofacitinib trials by Winthrop et al.³ evaluated the number and severity of HZ infections. Interestingly, HZ infections occurred more frequently in participants in the RA clinical trials, with about 11% having an infection compared to 5% in the PsA studies, once again highlighting a potential immunodeficiency particular to people with RA. Most patients had mild to moderate infections, but a small proportion of patients (<5%) had severe infections. Given the possibility of a reduced vaccine response, though unknown, after HZ vaccination in people with RA, consideration should be given not only to vaccination prior to initiation of JAK inhibitor therapy, but to assessment of vaccine efficacy and the ideal dosing schedules in these patients.

References

1. Wang Y et al. Increased risk of COVID-19 in patients with rheumatoid arthritis: a general population-based cohort study. Arthritis Care Res (Hoboken) 2021(Dec 7). 
2. Iancovici L et al. Rheumatoid arthritis patients treated with Janus kinase inhibitors show reduced humoral immune responses following BNT162b2 vaccination. Rheumatology (Oxford). 2021:keab879 (Nov 25).
3. Winthrop KL et al. Clinical management of herpes zoster in patients with rheumatoid arthritis or psoriatic arthritis receiving tofacitinib treatment. Rheumatol Ther. 2021 (Dec 6).

Along with long-standing concerns about immunodeficiency and use of immunosuppressive medication in people with rheumatoid arthritis (RA) are juxtaposed concerns about their additional risk of COVID-19 during the pandemic. Several studies have reported a high risk of severe COVID-19 outcomes in people with rheumatic disease, though few have compared this risk to the general population. This cohort study by Wang et al.¹ examines the risk of COVID-19 in people with RA compared to people with OA and the general population based on an electronic medical record database in the UK. The rate of COVID-19 was higher among people with RA than the general population, with a hazard ratio of 1.42 for confirmed COVID-19 cases, while the rate among people with OA was not increased. This finding confirms suspicions, though, due to the study design, it does not lend additional insight into nuances given the lack of information about RA treatment and activity as in prior studies.

Also of concern in the midst of the pandemic is the effect of RA and its treatment on response to vaccines against SARS-CoV-2. The rapid development of mRNA vaccines has been a boon, but research on vaccine response in people with rheumatic disease has suggested that certain medications can impact antibody formation. Iancovici et al.² examined antibody and B cell responses after vaccination in people with RA being treated with Janus kinase (JAK)-inhibitors or tumor necrosis factor (TNF)-inhibitors and in healthy volunteers. Though the study is flawed as responses were not assessed at the same timepoint after vaccination in all subjects and limited due to the heterogeneity of treatment and small numbers of subjects, antibody production and other assays were decreased in RA subjects, suggesting reduced humoral immunity. Whether a pause in JAK inhibitor treatment, as recommended by the American College of Rheumatology, makes an appreciable difference in these assessments of vaccine response is as yet unknown. Further, given the limited data, it is unclear whether having RA on its own, rather than the treatments involved, was the causative factor. Research is already underway on SARS-CoV-2 vaccine response in people with RA and other rheumatic diseases, but studies such as these also imply a relative immunodeficiency due to the diseases and their treatment that could extend to other vaccines or infections.

In addition to impacts on SARS-CoV-2 vaccine response, treatment with JAK inhibitors is known to increase risk of herpes zoster (HZ). A post hoc analysis of pooled data from 21 RA and 3 psoriatic arthritis (PsA) tofacitinib trials by Winthrop et al.³ evaluated the number and severity of HZ infections. Interestingly, HZ infections occurred more frequently in participants in the RA clinical trials, with about 11% having an infection compared to 5% in the PsA studies, once again highlighting a potential immunodeficiency particular to people with RA. Most patients had mild to moderate infections, but a small proportion of patients (<5%) had severe infections. Given the possibility of a reduced vaccine response, though unknown, after HZ vaccination in people with RA, consideration should be given not only to vaccination prior to initiation of JAK inhibitor therapy, but to assessment of vaccine efficacy and the ideal dosing schedules in these patients.

References

1. Wang Y et al. Increased risk of COVID-19 in patients with rheumatoid arthritis: a general population-based cohort study. Arthritis Care Res (Hoboken) 2021(Dec 7). 
2. Iancovici L et al. Rheumatoid arthritis patients treated with Janus kinase inhibitors show reduced humoral immune responses following BNT162b2 vaccination. Rheumatology (Oxford). 2021:keab879 (Nov 25).
3. Winthrop KL et al. Clinical management of herpes zoster in patients with rheumatoid arthritis or psoriatic arthritis receiving tofacitinib treatment. Rheumatol Ther. 2021 (Dec 6).