COVID-19

Key clinical point: Continuous positive airway pressure (CPAP) therapy in patients with severe COVID-19 who are not likely to benefit from invasive mechanical ventilation (IMV) does not confer a survival advantage over oxygen alone.

Major finding: The overall 30-day mortality rate was 75.6% in the oxygen group vs 77.7% in the CPAP group (Pearson’s Chi-square, P = .8).

Study details: The data come from a retrospective multicentre cohort study involving 479 patients with COVID-19 ineligible for IMV from 7 UK hospitals. Patients given CPAP were compared with those receiving oxygen therapy.

Disclosures: L Pearmain is supported by the Medical Research Council, and TW Felton is supported by the National Institute for Health Research Manchester Biomedical Research Centre. AB reported relationships with Fisher and Paykel and Sanofi Genzyme. The remaining authors declared no conflict of interests.

Source: Bradley P et al. EClinicalMedicine. 2021 Sep 8. doi: 10.1016/j.eclinm.2021.101122.

Key clinical point: Continuous positive airway pressure (CPAP) therapy in patients with severe COVID-19 who are not likely to benefit from invasive mechanical ventilation (IMV) does not confer a survival advantage over oxygen alone.

Major finding: The overall 30-day mortality rate was 75.6% in the oxygen group vs 77.7% in the CPAP group (Pearson’s Chi-square, P = .8).

Study details: The data come from a retrospective multicentre cohort study involving 479 patients with COVID-19 ineligible for IMV from 7 UK hospitals. Patients given CPAP were compared with those receiving oxygen therapy.

Disclosures: L Pearmain is supported by the Medical Research Council, and TW Felton is supported by the National Institute for Health Research Manchester Biomedical Research Centre. AB reported relationships with Fisher and Paykel and Sanofi Genzyme. The remaining authors declared no conflict of interests.

Source: Bradley P et al. EClinicalMedicine. 2021 Sep 8. doi: 10.1016/j.eclinm.2021.101122.

Key clinical point: Continuous positive airway pressure (CPAP) therapy in patients with severe COVID-19 who are not likely to benefit from invasive mechanical ventilation (IMV) does not confer a survival advantage over oxygen alone.

Major finding: The overall 30-day mortality rate was 75.6% in the oxygen group vs 77.7% in the CPAP group (Pearson’s Chi-square, P = .8).

Study details: The data come from a retrospective multicentre cohort study involving 479 patients with COVID-19 ineligible for IMV from 7 UK hospitals. Patients given CPAP were compared with those receiving oxygen therapy.

Disclosures: L Pearmain is supported by the Medical Research Council, and TW Felton is supported by the National Institute for Health Research Manchester Biomedical Research Centre. AB reported relationships with Fisher and Paykel and Sanofi Genzyme. The remaining authors declared no conflict of interests.

Source: Bradley P et al. EClinicalMedicine. 2021 Sep 8. doi: 10.1016/j.eclinm.2021.101122.

Key clinical point: Smokers have a significantly higher risk for COVID-19 related hospital admission and mortality than nonsmokers.

Major finding: Current smokers had an 80% higher risk for hospitalization than never-smokers (odds ratio, 1.80; 95% confidence interval, 1.26-2.29). Smokers who smoked more than 20 cigarettes a day had a 6.11-fold higher risk of dying from COVID-19 than never-smokers.

Study details: The data come from an observational study of 421,469 individuals from the UK Biobank.

Disclosures: The study was supported by individual grants to several authors. PS Tan, CAC Coupland, MR Munafò, J Hippisley-Cox, and A von Ende reported relationships with pharmaceutical companies and/or research organizations. The remaining authors declared no conflict of interests.

Source: Clift AK et al. Thorax. 2021 Sep 27. doi: 10.1136/thoraxjnl-2021-217080.

Key clinical point: Smokers have a significantly higher risk for COVID-19 related hospital admission and mortality than nonsmokers.

Major finding: Current smokers had an 80% higher risk for hospitalization than never-smokers (odds ratio, 1.80; 95% confidence interval, 1.26-2.29). Smokers who smoked more than 20 cigarettes a day had a 6.11-fold higher risk of dying from COVID-19 than never-smokers.

Study details: The data come from an observational study of 421,469 individuals from the UK Biobank.

Disclosures: The study was supported by individual grants to several authors. PS Tan, CAC Coupland, MR Munafò, J Hippisley-Cox, and A von Ende reported relationships with pharmaceutical companies and/or research organizations. The remaining authors declared no conflict of interests.

Source: Clift AK et al. Thorax. 2021 Sep 27. doi: 10.1136/thoraxjnl-2021-217080.

Key clinical point: Smokers have a significantly higher risk for COVID-19 related hospital admission and mortality than nonsmokers.

Major finding: Current smokers had an 80% higher risk for hospitalization than never-smokers (odds ratio, 1.80; 95% confidence interval, 1.26-2.29). Smokers who smoked more than 20 cigarettes a day had a 6.11-fold higher risk of dying from COVID-19 than never-smokers.

Study details: The data come from an observational study of 421,469 individuals from the UK Biobank.

Disclosures: The study was supported by individual grants to several authors. PS Tan, CAC Coupland, MR Munafò, J Hippisley-Cox, and A von Ende reported relationships with pharmaceutical companies and/or research organizations. The remaining authors declared no conflict of interests.

Source: Clift AK et al. Thorax. 2021 Sep 27. doi: 10.1136/thoraxjnl-2021-217080.

Key clinical point: Patients with multiple sclerosis (MS) receiving anti-CD20 (aCD20) treatment demonstrate a robust T-cell response to an mRNA COVID-19 vaccines.

Major finding: Thirty days following the second dose of an mRNA COVID-19 vaccine, 89% of patients with MS had antispike antibodies, and 50% had mounted anti-receptor-binding domain responses.

Study details: A study assessed antibody and T-cell responses in 20 patients with MS receiving aCD20 treatment and 10 healthy controls.

Disclosures: The study was supported by individual grants to several authors. SE Hensley, EJ Wherry, A Sette, ET Luning Prak, D Jacobs, and A Bar-Or reported relationships with pharmaceutical companies and/or research organizations. The remaining authors declared no conflict of interests.

Source: Apostolidis SA et al. Nat Med. 2021 Sep 14. doi: 10.1038/s41591-021-01507-2.

Key clinical point: Patients with multiple sclerosis (MS) receiving anti-CD20 (aCD20) treatment demonstrate a robust T-cell response to an mRNA COVID-19 vaccines.

Major finding: Thirty days following the second dose of an mRNA COVID-19 vaccine, 89% of patients with MS had antispike antibodies, and 50% had mounted anti-receptor-binding domain responses.

Study details: A study assessed antibody and T-cell responses in 20 patients with MS receiving aCD20 treatment and 10 healthy controls.

Disclosures: The study was supported by individual grants to several authors. SE Hensley, EJ Wherry, A Sette, ET Luning Prak, D Jacobs, and A Bar-Or reported relationships with pharmaceutical companies and/or research organizations. The remaining authors declared no conflict of interests.

Source: Apostolidis SA et al. Nat Med. 2021 Sep 14. doi: 10.1038/s41591-021-01507-2.

Key clinical point: Patients with multiple sclerosis (MS) receiving anti-CD20 (aCD20) treatment demonstrate a robust T-cell response to an mRNA COVID-19 vaccines.

Major finding: Thirty days following the second dose of an mRNA COVID-19 vaccine, 89% of patients with MS had antispike antibodies, and 50% had mounted anti-receptor-binding domain responses.

Study details: A study assessed antibody and T-cell responses in 20 patients with MS receiving aCD20 treatment and 10 healthy controls.

Disclosures: The study was supported by individual grants to several authors. SE Hensley, EJ Wherry, A Sette, ET Luning Prak, D Jacobs, and A Bar-Or reported relationships with pharmaceutical companies and/or research organizations. The remaining authors declared no conflict of interests.

Source: Apostolidis SA et al. Nat Med. 2021 Sep 14. doi: 10.1038/s41591-021-01507-2.

Key clinical point: A study has identified at least 3 modifiable behaviors that may increase the personal risk for COVID-19.

Major finding: Higher number of nonhousehold contacts (odds ratio [OR], 1.10 per 10 contacts; P = .024), attending events having at least 10 people (OR, 1.26 per 10 events; P = .007), and visiting restaurants (OR, 1.95 per 10 visits; P less than .001) were associated with a significantly increased risk for incident COVID-19.

Study details: The data come from a prospective cohort study of 28,575 individuals across 99 countries.

Disclosures: The study was supported by grants from the National Institutes of Health/National Institute of Biomedical Imaging and Bioengineering to GM Marcus, J Olgin, and M Pletcher. The authors declared no competing interests.

Source: Lin A et al. BMJ Open. 2021 Sep 21. doi: 10.1136/bmjopen-2021-052025.

Key clinical point: A study has identified at least 3 modifiable behaviors that may increase the personal risk for COVID-19.

Major finding: Higher number of nonhousehold contacts (odds ratio [OR], 1.10 per 10 contacts; P = .024), attending events having at least 10 people (OR, 1.26 per 10 events; P = .007), and visiting restaurants (OR, 1.95 per 10 visits; P less than .001) were associated with a significantly increased risk for incident COVID-19.

Study details: The data come from a prospective cohort study of 28,575 individuals across 99 countries.

Disclosures: The study was supported by grants from the National Institutes of Health/National Institute of Biomedical Imaging and Bioengineering to GM Marcus, J Olgin, and M Pletcher. The authors declared no competing interests.

Source: Lin A et al. BMJ Open. 2021 Sep 21. doi: 10.1136/bmjopen-2021-052025.

Key clinical point: A study has identified at least 3 modifiable behaviors that may increase the personal risk for COVID-19.

Major finding: Higher number of nonhousehold contacts (odds ratio [OR], 1.10 per 10 contacts; P = .024), attending events having at least 10 people (OR, 1.26 per 10 events; P = .007), and visiting restaurants (OR, 1.95 per 10 visits; P less than .001) were associated with a significantly increased risk for incident COVID-19.

Study details: The data come from a prospective cohort study of 28,575 individuals across 99 countries.

Disclosures: The study was supported by grants from the National Institutes of Health/National Institute of Biomedical Imaging and Bioengineering to GM Marcus, J Olgin, and M Pletcher. The authors declared no competing interests.

Source: Lin A et al. BMJ Open. 2021 Sep 21. doi: 10.1136/bmjopen-2021-052025.

Key clinical point: The risk of contracting COVID-19 among nonimmune family members decreases as the number of immune family members increases.

Major finding: An inverse dose-response association was seen between the number of immune members in each family and the risk for incident COVID-19 in nonimmune family members. Families with 1 immune member had a 45%-61% lower risk for COVID-19, whereas families with 4 immune members had a 97% lower risk.

Study details: The data come from an analysis of 1,789,728 individuals from 814,806 families, consisting of 2-5 members each.

Disclosures: Information on funding was not available. The authors declared no competing interests.

Source: Nordström P et al. JAMA Intern Med. 2021 Oct 11. doi: 10.1001/jamainternmed.2021.5814.

Key clinical point: The risk of contracting COVID-19 among nonimmune family members decreases as the number of immune family members increases.

Major finding: An inverse dose-response association was seen between the number of immune members in each family and the risk for incident COVID-19 in nonimmune family members. Families with 1 immune member had a 45%-61% lower risk for COVID-19, whereas families with 4 immune members had a 97% lower risk.

Study details: The data come from an analysis of 1,789,728 individuals from 814,806 families, consisting of 2-5 members each.

Disclosures: Information on funding was not available. The authors declared no competing interests.

Source: Nordström P et al. JAMA Intern Med. 2021 Oct 11. doi: 10.1001/jamainternmed.2021.5814.

Key clinical point: The risk of contracting COVID-19 among nonimmune family members decreases as the number of immune family members increases.

Major finding: An inverse dose-response association was seen between the number of immune members in each family and the risk for incident COVID-19 in nonimmune family members. Families with 1 immune member had a 45%-61% lower risk for COVID-19, whereas families with 4 immune members had a 97% lower risk.

Study details: The data come from an analysis of 1,789,728 individuals from 814,806 families, consisting of 2-5 members each.

Disclosures: Information on funding was not available. The authors declared no competing interests.

Source: Nordström P et al. JAMA Intern Med. 2021 Oct 11. doi: 10.1001/jamainternmed.2021.5814.

Key clinical point: In patients receiving high-flow nasal cannula (HFNC) for acute hypoxemic respiratory failure associated with COVID-19, initiating awake prone positioning (proning) soon after HFNC may improve survival.

Major finding: Initiating awake proning within 24 hours of HFNC was associated with lower mortality rates than late proning (26% vs 45%; P = .039).

Study details: The data come from a post hoc analysis of a trial evaluating awake proning in HFNC-treated patients with COVID-19 with respiratory failure (n=125).

Disclosures: The study was supported by the Rice Foundation. R Kaur, DL Vines, JD Scott, MW Trump, and J Li reported relationships with pharmaceutical/medical device companies and/or research organizations. The remaining authors declared no conflict of interests.

Source: Kaur R et al. Crit Care. 2021 Sep 17. doi: 10.1186/s13054-021-03761-9.

Key clinical point: In patients receiving high-flow nasal cannula (HFNC) for acute hypoxemic respiratory failure associated with COVID-19, initiating awake prone positioning (proning) soon after HFNC may improve survival.

Major finding: Initiating awake proning within 24 hours of HFNC was associated with lower mortality rates than late proning (26% vs 45%; P = .039).

Study details: The data come from a post hoc analysis of a trial evaluating awake proning in HFNC-treated patients with COVID-19 with respiratory failure (n=125).

Disclosures: The study was supported by the Rice Foundation. R Kaur, DL Vines, JD Scott, MW Trump, and J Li reported relationships with pharmaceutical/medical device companies and/or research organizations. The remaining authors declared no conflict of interests.

Source: Kaur R et al. Crit Care. 2021 Sep 17. doi: 10.1186/s13054-021-03761-9.

Key clinical point: In patients receiving high-flow nasal cannula (HFNC) for acute hypoxemic respiratory failure associated with COVID-19, initiating awake prone positioning (proning) soon after HFNC may improve survival.

Major finding: Initiating awake proning within 24 hours of HFNC was associated with lower mortality rates than late proning (26% vs 45%; P = .039).

Study details: The data come from a post hoc analysis of a trial evaluating awake proning in HFNC-treated patients with COVID-19 with respiratory failure (n=125).

Disclosures: The study was supported by the Rice Foundation. R Kaur, DL Vines, JD Scott, MW Trump, and J Li reported relationships with pharmaceutical/medical device companies and/or research organizations. The remaining authors declared no conflict of interests.

Source: Kaur R et al. Crit Care. 2021 Sep 17. doi: 10.1186/s13054-021-03761-9.

Key clinical point: Serum albumin levels at presentation may be a potential marker for COVID-19 severity and prognosis.

Major finding: Serum albumin of <3.5 g/dL was an independent risk factor for severe infection (adjusted odds ratio [aOR], 2.924; 95% confidence interval [CI], 1.509-5.664) and 30-day mortality (aOR, 2.615; 95% CI, 1.131-6.051).

Study details: A retrospective observational study included 296 patients with COVID-19 from emergency departments of 3 hospitals in Italy.

Disclosures: The study did not receive any funding. The authors declared no competing interests.

Source: Turcato G et al. Emerg Med J. 2021 Sep 21. doi: 10.1136/emermed-2020-210081.

Key clinical point: Serum albumin levels at presentation may be a potential marker for COVID-19 severity and prognosis.

Major finding: Serum albumin of <3.5 g/dL was an independent risk factor for severe infection (adjusted odds ratio [aOR], 2.924; 95% confidence interval [CI], 1.509-5.664) and 30-day mortality (aOR, 2.615; 95% CI, 1.131-6.051).

Study details: A retrospective observational study included 296 patients with COVID-19 from emergency departments of 3 hospitals in Italy.

Disclosures: The study did not receive any funding. The authors declared no competing interests.

Source: Turcato G et al. Emerg Med J. 2021 Sep 21. doi: 10.1136/emermed-2020-210081.

Key clinical point: Serum albumin levels at presentation may be a potential marker for COVID-19 severity and prognosis.

Major finding: Serum albumin of <3.5 g/dL was an independent risk factor for severe infection (adjusted odds ratio [aOR], 2.924; 95% confidence interval [CI], 1.509-5.664) and 30-day mortality (aOR, 2.615; 95% CI, 1.131-6.051).

Study details: A retrospective observational study included 296 patients with COVID-19 from emergency departments of 3 hospitals in Italy.

Disclosures: The study did not receive any funding. The authors declared no competing interests.

Source: Turcato G et al. Emerg Med J. 2021 Sep 21. doi: 10.1136/emermed-2020-210081.

Key clinical point: Critically ill patients with COVID-19 fail to benefit from convalescent plasma.

Major finding: The trial was stopped early after the probability of futility was calculated at 99.4%. Convalescent plasma vs. no plasma groups had 0 vs 3 organ support-free days, 37.3% vs 38.4% in-hospital mortality rates, and 14 vs 14 median days alive and free of organ support.

Study details: The data come from an open-label, randomized component of the ongoing REMAP-CAP trial (n=2,011). Critically ill adults with COVID-19 were randomly assigned to receive convalescent plasma or not.

Disclosures: The study was funded by nonprofits in multiple countries. Several authors reported relationships with pharmaceutical companies and/or research organizations.

Source: Estcourt LJ et al. JAMA. 2021 Oct 4. doi: 10.1001/jama.2021.18178.

Key clinical point: Critically ill patients with COVID-19 fail to benefit from convalescent plasma.

Major finding: The trial was stopped early after the probability of futility was calculated at 99.4%. Convalescent plasma vs. no plasma groups had 0 vs 3 organ support-free days, 37.3% vs 38.4% in-hospital mortality rates, and 14 vs 14 median days alive and free of organ support.

Study details: The data come from an open-label, randomized component of the ongoing REMAP-CAP trial (n=2,011). Critically ill adults with COVID-19 were randomly assigned to receive convalescent plasma or not.

Disclosures: The study was funded by nonprofits in multiple countries. Several authors reported relationships with pharmaceutical companies and/or research organizations.

Source: Estcourt LJ et al. JAMA. 2021 Oct 4. doi: 10.1001/jama.2021.18178.

Key clinical point: Critically ill patients with COVID-19 fail to benefit from convalescent plasma.

Major finding: The trial was stopped early after the probability of futility was calculated at 99.4%. Convalescent plasma vs. no plasma groups had 0 vs 3 organ support-free days, 37.3% vs 38.4% in-hospital mortality rates, and 14 vs 14 median days alive and free of organ support.

Study details: The data come from an open-label, randomized component of the ongoing REMAP-CAP trial (n=2,011). Critically ill adults with COVID-19 were randomly assigned to receive convalescent plasma or not.

Disclosures: The study was funded by nonprofits in multiple countries. Several authors reported relationships with pharmaceutical companies and/or research organizations.

Source: Estcourt LJ et al. JAMA. 2021 Oct 4. doi: 10.1001/jama.2021.18178.

Key clinical point: Pulmonary sequelae at 6 months after COVID-19 infection are more common in patients with diabetes or hyperglycemia compared with normoglycemic individuals.

Major finding: At 6 months, residual lung abnormalities on computed tomography were seen in 65.4%, 58.3%, and 36.6% of patients with preexisting diabetes, secondary hyperglycemia, and normoglycemia, respectively.

Study details: The data come from a retrospective study of 141 patients with COVID-19 at 2 hospitals in Wuhan, China.

Disclosures: The research was supported by the National Natural Science Foundation of China, National Key Research and Development Project of China, and Zhejiang University. The authors declared no competing interests.

Source: Li Y et al. Eur J Radiol. 2021 Oct 5. doi: 10.1016/j.ejrad.2021.109997.

Key clinical point: Pulmonary sequelae at 6 months after COVID-19 infection are more common in patients with diabetes or hyperglycemia compared with normoglycemic individuals.

Major finding: At 6 months, residual lung abnormalities on computed tomography were seen in 65.4%, 58.3%, and 36.6% of patients with preexisting diabetes, secondary hyperglycemia, and normoglycemia, respectively.

Study details: The data come from a retrospective study of 141 patients with COVID-19 at 2 hospitals in Wuhan, China.

Disclosures: The research was supported by the National Natural Science Foundation of China, National Key Research and Development Project of China, and Zhejiang University. The authors declared no competing interests.

Source: Li Y et al. Eur J Radiol. 2021 Oct 5. doi: 10.1016/j.ejrad.2021.109997.

Key clinical point: Pulmonary sequelae at 6 months after COVID-19 infection are more common in patients with diabetes or hyperglycemia compared with normoglycemic individuals.

Major finding: At 6 months, residual lung abnormalities on computed tomography were seen in 65.4%, 58.3%, and 36.6% of patients with preexisting diabetes, secondary hyperglycemia, and normoglycemia, respectively.

Study details: The data come from a retrospective study of 141 patients with COVID-19 at 2 hospitals in Wuhan, China.

Disclosures: The research was supported by the National Natural Science Foundation of China, National Key Research and Development Project of China, and Zhejiang University. The authors declared no competing interests.

Source: Li Y et al. Eur J Radiol. 2021 Oct 5. doi: 10.1016/j.ejrad.2021.109997.

Patients who are being treated with Janus kinase (JAK) inhibitors overall show a high immune response rate to COVID-19 vaccination, one that matches the rates seen in patients on other immunosuppressants, a new study has found.

The patients taking a JAK inhibitor who are most at risk of a diminished response may be those on upadacitinib (Rinvoq) and anyone 65 years or older, wrote Raphaèle Seror, MD, PhD, of Paris-Saclay (France) University and coauthors. The study was published in The Lancet Rheumatology.

To gauge the effectiveness of COVID-19 vaccines in this subset of immunosuppressed patients, the researchers analyzed 113 participants in the MAJIK-SFR Registry, a multicenter study of French patients with rheumatoid or psoriatic arthritis. The participants were treated at 13 centers throughout France; their mean age was 61.8 years (standard deviation, 12.5), and 72% were female. A total of 56 were taking baricitinib (Olumiant), 30 were taking tofacitinib (Xeljanz), and 27 were taking upadacitinib.

Serologic assessment was performed an average of 8.7 weeks (SD, 5.2) after the last dose of vaccine. The overall response rate – defined as the proportion of patients with detectable anti-spike antibodies per manufacturer’s cutoff values – was 88% (100 of 113). The nonresponse rate was higher with upadacitinib (7 of 27 patients, 26%) than with baricitinib (5 of 56, 9%) or tofacitinib (1 of 30, 3%). The only nonresponders who were not age 65 or older were four of the seven who received upadacitinib. The interval between the last vaccine dose and serologic assessment was somewhat longer in nonresponders (11.3 weeks) than in responders (8.3 weeks).

Earlier this year, the American College of Rheumatology recommended withholding JAK inhibitors for 1 week after each vaccine dose because of “concern related to the effects of this medication class on interferon signaling that may result in a diminished vaccine response Only two patients in the study had treatment with JAK inhibitors stopped before or after vaccination.

Questions about antibody levels remain difficult to answer

“This study does further confirm a big point,” said Alfred Kim, MD, PhD, of Washington University, St. Louis, in an interview. “Most people on any sort of immunosuppression, with rare exceptions, can mount responses to COVID-19 vaccination.”

“What level of response is going to be sufficient, of course, is not clear,” he added. “Even though most people generate responses, at the population level those responses seem lower than those in nonimmunosuppressed people. Particularly for those on upadacitinib, which is lower than patients on the other JAK inhibitors. Is that problematic? We don’t know yet.”

Dr. Kim, who was part of a separate, earlier study that assessed vaccine response in patients with chronic inflammatory disease who were being treated with immunosuppressive medications, noted that many of the questions patients are asking about their antibody levels cannot yet be answered.

“It’s kind of the Wild West of serologic testing out there right now,” he said. “Even though we’re recommending that people still don’t check their antibody levels because their results are largely inactionable, everyone is still getting them anyway. But each of these tests are slightly different, and the results and the interpretation are further clouded because of those slight performance differences between each platform.”

Dr. Kim highlighted the number of different tests as one of this study’s notable limitations: 11 different assays were used to determine patients’ immune responses. “The authors made the argument that these tests are FDA approved, and that’s true, but that doesn’t necessarily mean much. Approval does translate to technical reliability but not to comparisons between the tests.”

As for next steps, both the authors and Dr. Kim recognized the need for a prospective trial. “To do a vaccine effectiveness–type study and show clinical protection against either infection or hospitalization – those are going to take a while, simply because of the nature of how many people you need for each of these studies,” he said. “Time will tell whether or not the data that are being presented here will translate literally into protective outcomes downstream.”

The MAJIK Registry is supported by the French Rheumatology Society. The authors acknowledged numerous potential conflicts of interest, including receiving consulting fees, research support, and honoraria from various pharmaceutical companies.

Patients who are being treated with Janus kinase (JAK) inhibitors overall show a high immune response rate to COVID-19 vaccination, one that matches the rates seen in patients on other immunosuppressants, a new study has found.

The patients taking a JAK inhibitor who are most at risk of a diminished response may be those on upadacitinib (Rinvoq) and anyone 65 years or older, wrote Raphaèle Seror, MD, PhD, of Paris-Saclay (France) University and coauthors. The study was published in The Lancet Rheumatology.

To gauge the effectiveness of COVID-19 vaccines in this subset of immunosuppressed patients, the researchers analyzed 113 participants in the MAJIK-SFR Registry, a multicenter study of French patients with rheumatoid or psoriatic arthritis. The participants were treated at 13 centers throughout France; their mean age was 61.8 years (standard deviation, 12.5), and 72% were female. A total of 56 were taking baricitinib (Olumiant), 30 were taking tofacitinib (Xeljanz), and 27 were taking upadacitinib.

Serologic assessment was performed an average of 8.7 weeks (SD, 5.2) after the last dose of vaccine. The overall response rate – defined as the proportion of patients with detectable anti-spike antibodies per manufacturer’s cutoff values – was 88% (100 of 113). The nonresponse rate was higher with upadacitinib (7 of 27 patients, 26%) than with baricitinib (5 of 56, 9%) or tofacitinib (1 of 30, 3%). The only nonresponders who were not age 65 or older were four of the seven who received upadacitinib. The interval between the last vaccine dose and serologic assessment was somewhat longer in nonresponders (11.3 weeks) than in responders (8.3 weeks).

Earlier this year, the American College of Rheumatology recommended withholding JAK inhibitors for 1 week after each vaccine dose because of “concern related to the effects of this medication class on interferon signaling that may result in a diminished vaccine response Only two patients in the study had treatment with JAK inhibitors stopped before or after vaccination.

Questions about antibody levels remain difficult to answer

“This study does further confirm a big point,” said Alfred Kim, MD, PhD, of Washington University, St. Louis, in an interview. “Most people on any sort of immunosuppression, with rare exceptions, can mount responses to COVID-19 vaccination.”

“What level of response is going to be sufficient, of course, is not clear,” he added. “Even though most people generate responses, at the population level those responses seem lower than those in nonimmunosuppressed people. Particularly for those on upadacitinib, which is lower than patients on the other JAK inhibitors. Is that problematic? We don’t know yet.”

Dr. Kim, who was part of a separate, earlier study that assessed vaccine response in patients with chronic inflammatory disease who were being treated with immunosuppressive medications, noted that many of the questions patients are asking about their antibody levels cannot yet be answered.

“It’s kind of the Wild West of serologic testing out there right now,” he said. “Even though we’re recommending that people still don’t check their antibody levels because their results are largely inactionable, everyone is still getting them anyway. But each of these tests are slightly different, and the results and the interpretation are further clouded because of those slight performance differences between each platform.”

Dr. Kim highlighted the number of different tests as one of this study’s notable limitations: 11 different assays were used to determine patients’ immune responses. “The authors made the argument that these tests are FDA approved, and that’s true, but that doesn’t necessarily mean much. Approval does translate to technical reliability but not to comparisons between the tests.”

As for next steps, both the authors and Dr. Kim recognized the need for a prospective trial. “To do a vaccine effectiveness–type study and show clinical protection against either infection or hospitalization – those are going to take a while, simply because of the nature of how many people you need for each of these studies,” he said. “Time will tell whether or not the data that are being presented here will translate literally into protective outcomes downstream.”

The MAJIK Registry is supported by the French Rheumatology Society. The authors acknowledged numerous potential conflicts of interest, including receiving consulting fees, research support, and honoraria from various pharmaceutical companies.

Patients who are being treated with Janus kinase (JAK) inhibitors overall show a high immune response rate to COVID-19 vaccination, one that matches the rates seen in patients on other immunosuppressants, a new study has found.

The patients taking a JAK inhibitor who are most at risk of a diminished response may be those on upadacitinib (Rinvoq) and anyone 65 years or older, wrote Raphaèle Seror, MD, PhD, of Paris-Saclay (France) University and coauthors. The study was published in The Lancet Rheumatology.

To gauge the effectiveness of COVID-19 vaccines in this subset of immunosuppressed patients, the researchers analyzed 113 participants in the MAJIK-SFR Registry, a multicenter study of French patients with rheumatoid or psoriatic arthritis. The participants were treated at 13 centers throughout France; their mean age was 61.8 years (standard deviation, 12.5), and 72% were female. A total of 56 were taking baricitinib (Olumiant), 30 were taking tofacitinib (Xeljanz), and 27 were taking upadacitinib.

Serologic assessment was performed an average of 8.7 weeks (SD, 5.2) after the last dose of vaccine. The overall response rate – defined as the proportion of patients with detectable anti-spike antibodies per manufacturer’s cutoff values – was 88% (100 of 113). The nonresponse rate was higher with upadacitinib (7 of 27 patients, 26%) than with baricitinib (5 of 56, 9%) or tofacitinib (1 of 30, 3%). The only nonresponders who were not age 65 or older were four of the seven who received upadacitinib. The interval between the last vaccine dose and serologic assessment was somewhat longer in nonresponders (11.3 weeks) than in responders (8.3 weeks).

Earlier this year, the American College of Rheumatology recommended withholding JAK inhibitors for 1 week after each vaccine dose because of “concern related to the effects of this medication class on interferon signaling that may result in a diminished vaccine response Only two patients in the study had treatment with JAK inhibitors stopped before or after vaccination.

Questions about antibody levels remain difficult to answer

“This study does further confirm a big point,” said Alfred Kim, MD, PhD, of Washington University, St. Louis, in an interview. “Most people on any sort of immunosuppression, with rare exceptions, can mount responses to COVID-19 vaccination.”

“What level of response is going to be sufficient, of course, is not clear,” he added. “Even though most people generate responses, at the population level those responses seem lower than those in nonimmunosuppressed people. Particularly for those on upadacitinib, which is lower than patients on the other JAK inhibitors. Is that problematic? We don’t know yet.”

Dr. Kim, who was part of a separate, earlier study that assessed vaccine response in patients with chronic inflammatory disease who were being treated with immunosuppressive medications, noted that many of the questions patients are asking about their antibody levels cannot yet be answered.

“It’s kind of the Wild West of serologic testing out there right now,” he said. “Even though we’re recommending that people still don’t check their antibody levels because their results are largely inactionable, everyone is still getting them anyway. But each of these tests are slightly different, and the results and the interpretation are further clouded because of those slight performance differences between each platform.”

Dr. Kim highlighted the number of different tests as one of this study’s notable limitations: 11 different assays were used to determine patients’ immune responses. “The authors made the argument that these tests are FDA approved, and that’s true, but that doesn’t necessarily mean much. Approval does translate to technical reliability but not to comparisons between the tests.”

As for next steps, both the authors and Dr. Kim recognized the need for a prospective trial. “To do a vaccine effectiveness–type study and show clinical protection against either infection or hospitalization – those are going to take a while, simply because of the nature of how many people you need for each of these studies,” he said. “Time will tell whether or not the data that are being presented here will translate literally into protective outcomes downstream.”

The MAJIK Registry is supported by the French Rheumatology Society. The authors acknowledged numerous potential conflicts of interest, including receiving consulting fees, research support, and honoraria from various pharmaceutical companies.