Federal Practitioner

Chronic obstructive pulmonary disease (COPD) has been the third leading cause of death in the US since 2008.¹ Current management of COPD includes smoking cessation, adequate nutrition, medication therapy, pulmonary rehabilitation, and vaccines.² Outside of pharmacologic management, oxygen therapy has become a staple treatment of chronic hypoxemic respiratory failure due to COPD. Landmark trials, including the Nocturnal Oxygen Therapy Trial (NOTT) and Medical Research Council (MRC) study, demonstrated improved survival in patients with COPD and hypoxemia, particularly if these patients received oxygen for 18 hours per day.^3,4 NOTT prospectively evaluated 203 patients at 6 centers who were randomly allocated to either continuous oxygen therapy or 12-hour nocturnal oxygen therapy. The overall mortality in the nocturnal oxygen therapy group was 1.94 times that in the continuous oxygen therapy group (P = .01).³ The MRC study included 87 patients who were randomized to oxygen therapy or no oxygen; risk of death was 12% per year in the treated group vs 29% per year in the control group (P = .04).⁴ The effectiveness of long-term oxygen therapy (LTOT) in active smokers continues to be a source of debate; although 50% of patients in the NOTT trial were smokers, there was no subgroup analysis of whether smoking status had an impact on survival in those on continuous oxygen therapy.

Although many therapies are available for the treatment of COPD, the most effective treatment to prevent the progression of COPD is smoking cessation. Resources like smoking cessation programs, nicotine patches, and medications, such as bupropion and varenicline, are available to aid smoking cessation.⁵ However, many patients are unable to quit tobacco use despite their best efforts using available resources, and they continue to smoke even with progressive COPD. Long-time smokers also are likely to continue smoking while on LTOT, which increases their risk for fire-related injury.^6-8

Traditional indications are being scrutinized after the LTOT trial found no benefit with respect to time to death or first hospitalization among patients with stable COPD and resting or exercise-induced moderate desaturation.⁹

Although oxygen accelerates combustion and is a potential fire hazard, LTOT has been prescribed even to active smokers as the 2 landmark trials did not exclude patients who were active smokers from receiving oxygen therapy.^3,4 Therefore, LTOT has traditionally been prescribed to veterans who are actively smoking, despite the fire hazard. Attempts at mitigating hazards related to oxygen therapy in active smokers include counseling extensively about safety measures (which includes avoiding open flames such as candles, large fires, or sparks when on LTOT and providing Home Safety Agreements—a written contract between prescriber and patient wherein the patient agrees to abide by the terms of the US Department of Veterans Affairs (VA) to mitigate hazards related to LTOT in order to receive LTOT (eAppendix 

Methods

With this practice in mind, we conducted an institutional review board approved retrospective chart review of all veterans with diagnosis of COPD within the Central Texas Veterans Health Care System (CTVHCS) who were prescribed new LTOT between October 1, 2010 and September 30, 2015. Given the retrospective nature of the chart review, patient consent was not obtained. Inclusion criteria were veterans aged > 18 years who had a confirmed diagnosis of COPD by spirometry and who met criteria for either continuous or ambulation- only oxygen therapy.

Criteria for exclusion included patients with hypoxemia not solely attributable to COPD or due to diseases other than COPD. We reviewed encounters in these patients’ charts, including follow-up in the clinic of the providers prescribing oxygen, to assess for fire-related incidents, defined as events wherein fire was visualized by the patient or by individuals living with the patient and with report provided to medical equipment company providing oxygen; the patient did not have to seek medical care to qualify for fire-related incident. Of the 158 patients who met the criteria for inclusion in the study, 152 were male.

Statistics

Bayesian logistic regression was used to model the outcome variable fire-related incident with the predictors smoking status, age, race, depression, PTSD, and type of oxygen used. Mental health disorders have significant effect on substance use disorders, such as alcohol use. Depression and PTSD were more common mental health diagnoses found in our patient population. Additionally, due to the small sample size, these psychiatric diagnoses were chosen to evaluate the impact of mental health disorders on firerelated events.

Although the sample size of events was small, weakly informative normal priors (0, 2.5) were used to shrink parameter estimates toward 0 and minimize overfitting. Weakly informative normal priors have also been suggested to deal with the problem of quasi-complete separation, where in our case, both smoking and no-PTSD perfectly predicted the 9 fire-related incidents.¹⁰ All input variables were centered and scaled as recommended. ⁹ The model fit well as assessed by posterior predictive checks, and Rhat was 1.00 for all parameters, indicating that all chains converged. Analysis was completed in R version 3.5.1 using the ‘brms’ package for Bayesian modeling.¹¹

Results

The mean age for the 158 included patients was 71.3 years in nonsmokers and 65.9 years in smokers. Fifty-three of the included patients were active smokers when LTOT was initiated. Nine veterans had fire-related incidents during the study period. All 9 patients were actively smoking (about 17%) at the time of the fire incidents. There were no deaths, and 5 patients required hospitalization due to facial burns resulting from the fire-related incidents. Our study focused on 5 baseline characteristics in our population (Table 1). After gathering data, our group inferred that these characteristics had a potential relationship to fire-related incidents compared with other variables that were studied. Future studies could look at other patient characteristics that may be linked to fire-related incidents in patients on LTOT. For example, not having PTSD also perfectly predicts fire-related incidents in our data (ie, none of the participants who had fire-related incidents had PTSD). Although this finding was not within the 95% confidence interval (CI) in the model, it does show that care must be taken when interpreting effects from small samples (Table 2). The modelestimated odds of a fire-related incident occurring in a smoker were 31.6 (5.1-372.7) times more likely than were the odds of a firerelated incident occurring in a nonsmoker, holding all other predictors at their reference level; 95% CI for the odds ratios for all other predictors in the model included a value of 1.

Discussion

This study showed evidence of increased odds of fire-related events in actively smoking patients receiving LTOT compared with patients who do not actively smoke while attempting to adjust for potential confounders. Of the 9 patients who had fire events, 5 required hospitalization for burns.

A similar retrospective cohort study by Sharma and colleagues in 2015 demonstrated an increased risk of burn-related injury when on LTOT but reiterated that the benefit of oxygen outweighs the risk of burn-related injury in patients requiring oxygen therapy.¹² Interestingly, Sharma and colleagues were unable to identify smoking status for the patients studied but further identified factors associated with burn injury to include male sex, low socioeconomic status, oxygen therapy use, and ≥ 3 comorbidities. The study’s conclusion recommended continued education by health care professionals (HCPs) to their patients on LTOT regarding potential for burn injury. In the same vein, the VA National Center for Ethics in Health Care noted that “clinicians should familiarize themselves with the risks and benefits of LTOT; should inform their patients of the risks and benefits without exaggerating the risk associated with smoking; avoid undue coercion inherent in the clinician’s ability to withdraw LTOT; reduce the risk to the greatest degree possible; and consider termination of LTOT in very extreme cases and in consultation with a multidisciplinary committee.”¹³

This statement is in contrast to the guidelines and policies of other countries, such as Sweden, where smoking is a direct contraindication for prescription of oxygen therapy, or in Australia and New Zealand, where the Thoracic Society of Australia and New Zealand oxygen therapy guidelines recommend against prescription of LTOT, citing “increased fire risk and the probability that the poorer prognosis conferred by smoking will offset treatment benefit.”^6,14

The prevalence of oxygen therapy introduces the potential for fire-related incidents with subsequent injury requiring medical care. There are few studies regarding home oxygen fire in the US due to the lack of a uniform reporting system. One study by Wendling and Pelletier analyzed deaths in Maine, Massachusetts, New Hampshire, and Oklahoma between 2000 and 2007 and found 38 deaths directly attributable to home oxygen fires as a result of smoking^.15 Further, the Consumer Product Safety Commission’s National Electronic Injury Surveillance System between 2003 and 2006 attributed 1,190 thermal burns related to home oxygen fires; the majority of which were ignited by tobacco smoking.¹⁵ The Swedish National Register of Respiratory Failure (Swedevox) published prospective population-based, consecutive cohort study that collected data over 17 years and evaluated the risk of fire-related incident in those on LTOT. Of the 12,497 patients sampled, 17 had a burn injury and 2 patients died. The low incidence of burn injury on LTOT was attributed to the strict guidelines instituted in Sweden for doctors to avoid prescribing LTOT to actively smoking patients.⁶ A follow-up study by Tanash and colleagues compared the risk of burn injury in each country, respectively. The results found an increased number of burn injuries in those on oxygen therapy in Denmark, a country with fewer restrictions on smoking compared with those of Sweden.⁷ Similarly, our results showed that the rate of fire and burn injuries was exclusively among veterans who were active smokers. All patients who were prescribed oxygen therapy at CTVHCS received counseling and signed Home Safety Agreements. Despite following the recommendations set forth by the VA on counseling, extensive harm reduction techniques, and close follow-up, we found there was still a high incidence of fires in veterans with COPD on LTOT who continue to smoke.

The findings from our study concur with those previously published regarding the risk of home oxygen fire and concomitant smoking, supporting the idea for more regulated and concrete guidelines for prescribing LTOT to those requiring it.⁸

Limitations

The major limitation was the small sample size of our study. Another limitation was that our study population is predominantly male as is common in veteran cohorts. In fiscal year 2016, the veteran population of Texas was 1,434,361 males and 168,967 females.¹⁶ According to Franklin and colleagues, HCPs noticed an increase use of long-term oxygen among women compared with that of men.¹⁷

Conclusions

Our study showed an increased odds of firerelated incidents of patients while on LTOT, strengthening the argument that even with extensive education, those who smoke and are on LTOT continue to put themselves at risk of a fire-related incident. This finding stresses the importance of continuing patient education on the importance of smoking cessation prior to administration of LTOT or avoiding fire hazards while on LTOT. Further research into LTOT and fire hazards could help in implementing a more structured approval process for patients who want to obtain LTOT. We propose further studies evaluating risk factors for the incidence of fire events among patients prescribed LTOT. A growing and aging population with a need for LTOT necessitates examination of oxygen safe prescribing.

Chronic obstructive pulmonary disease (COPD) has been the third leading cause of death in the US since 2008.¹ Current management of COPD includes smoking cessation, adequate nutrition, medication therapy, pulmonary rehabilitation, and vaccines.² Outside of pharmacologic management, oxygen therapy has become a staple treatment of chronic hypoxemic respiratory failure due to COPD. Landmark trials, including the Nocturnal Oxygen Therapy Trial (NOTT) and Medical Research Council (MRC) study, demonstrated improved survival in patients with COPD and hypoxemia, particularly if these patients received oxygen for 18 hours per day.^3,4 NOTT prospectively evaluated 203 patients at 6 centers who were randomly allocated to either continuous oxygen therapy or 12-hour nocturnal oxygen therapy. The overall mortality in the nocturnal oxygen therapy group was 1.94 times that in the continuous oxygen therapy group (P = .01).³ The MRC study included 87 patients who were randomized to oxygen therapy or no oxygen; risk of death was 12% per year in the treated group vs 29% per year in the control group (P = .04).⁴ The effectiveness of long-term oxygen therapy (LTOT) in active smokers continues to be a source of debate; although 50% of patients in the NOTT trial were smokers, there was no subgroup analysis of whether smoking status had an impact on survival in those on continuous oxygen therapy.

Although many therapies are available for the treatment of COPD, the most effective treatment to prevent the progression of COPD is smoking cessation. Resources like smoking cessation programs, nicotine patches, and medications, such as bupropion and varenicline, are available to aid smoking cessation.⁵ However, many patients are unable to quit tobacco use despite their best efforts using available resources, and they continue to smoke even with progressive COPD. Long-time smokers also are likely to continue smoking while on LTOT, which increases their risk for fire-related injury.^6-8

Traditional indications are being scrutinized after the LTOT trial found no benefit with respect to time to death or first hospitalization among patients with stable COPD and resting or exercise-induced moderate desaturation.⁹

Although oxygen accelerates combustion and is a potential fire hazard, LTOT has been prescribed even to active smokers as the 2 landmark trials did not exclude patients who were active smokers from receiving oxygen therapy.^3,4 Therefore, LTOT has traditionally been prescribed to veterans who are actively smoking, despite the fire hazard. Attempts at mitigating hazards related to oxygen therapy in active smokers include counseling extensively about safety measures (which includes avoiding open flames such as candles, large fires, or sparks when on LTOT and providing Home Safety Agreements—a written contract between prescriber and patient wherein the patient agrees to abide by the terms of the US Department of Veterans Affairs (VA) to mitigate hazards related to LTOT in order to receive LTOT (eAppendix 

Methods

With this practice in mind, we conducted an institutional review board approved retrospective chart review of all veterans with diagnosis of COPD within the Central Texas Veterans Health Care System (CTVHCS) who were prescribed new LTOT between October 1, 2010 and September 30, 2015. Given the retrospective nature of the chart review, patient consent was not obtained. Inclusion criteria were veterans aged > 18 years who had a confirmed diagnosis of COPD by spirometry and who met criteria for either continuous or ambulation- only oxygen therapy.

Criteria for exclusion included patients with hypoxemia not solely attributable to COPD or due to diseases other than COPD. We reviewed encounters in these patients’ charts, including follow-up in the clinic of the providers prescribing oxygen, to assess for fire-related incidents, defined as events wherein fire was visualized by the patient or by individuals living with the patient and with report provided to medical equipment company providing oxygen; the patient did not have to seek medical care to qualify for fire-related incident. Of the 158 patients who met the criteria for inclusion in the study, 152 were male.

Statistics

Bayesian logistic regression was used to model the outcome variable fire-related incident with the predictors smoking status, age, race, depression, PTSD, and type of oxygen used. Mental health disorders have significant effect on substance use disorders, such as alcohol use. Depression and PTSD were more common mental health diagnoses found in our patient population. Additionally, due to the small sample size, these psychiatric diagnoses were chosen to evaluate the impact of mental health disorders on firerelated events.

Although the sample size of events was small, weakly informative normal priors (0, 2.5) were used to shrink parameter estimates toward 0 and minimize overfitting. Weakly informative normal priors have also been suggested to deal with the problem of quasi-complete separation, where in our case, both smoking and no-PTSD perfectly predicted the 9 fire-related incidents.¹⁰ All input variables were centered and scaled as recommended. ⁹ The model fit well as assessed by posterior predictive checks, and Rhat was 1.00 for all parameters, indicating that all chains converged. Analysis was completed in R version 3.5.1 using the ‘brms’ package for Bayesian modeling.¹¹

Results

The mean age for the 158 included patients was 71.3 years in nonsmokers and 65.9 years in smokers. Fifty-three of the included patients were active smokers when LTOT was initiated. Nine veterans had fire-related incidents during the study period. All 9 patients were actively smoking (about 17%) at the time of the fire incidents. There were no deaths, and 5 patients required hospitalization due to facial burns resulting from the fire-related incidents. Our study focused on 5 baseline characteristics in our population (Table 1). After gathering data, our group inferred that these characteristics had a potential relationship to fire-related incidents compared with other variables that were studied. Future studies could look at other patient characteristics that may be linked to fire-related incidents in patients on LTOT. For example, not having PTSD also perfectly predicts fire-related incidents in our data (ie, none of the participants who had fire-related incidents had PTSD). Although this finding was not within the 95% confidence interval (CI) in the model, it does show that care must be taken when interpreting effects from small samples (Table 2). The modelestimated odds of a fire-related incident occurring in a smoker were 31.6 (5.1-372.7) times more likely than were the odds of a firerelated incident occurring in a nonsmoker, holding all other predictors at their reference level; 95% CI for the odds ratios for all other predictors in the model included a value of 1.

Discussion

This study showed evidence of increased odds of fire-related events in actively smoking patients receiving LTOT compared with patients who do not actively smoke while attempting to adjust for potential confounders. Of the 9 patients who had fire events, 5 required hospitalization for burns.

A similar retrospective cohort study by Sharma and colleagues in 2015 demonstrated an increased risk of burn-related injury when on LTOT but reiterated that the benefit of oxygen outweighs the risk of burn-related injury in patients requiring oxygen therapy.¹² Interestingly, Sharma and colleagues were unable to identify smoking status for the patients studied but further identified factors associated with burn injury to include male sex, low socioeconomic status, oxygen therapy use, and ≥ 3 comorbidities. The study’s conclusion recommended continued education by health care professionals (HCPs) to their patients on LTOT regarding potential for burn injury. In the same vein, the VA National Center for Ethics in Health Care noted that “clinicians should familiarize themselves with the risks and benefits of LTOT; should inform their patients of the risks and benefits without exaggerating the risk associated with smoking; avoid undue coercion inherent in the clinician’s ability to withdraw LTOT; reduce the risk to the greatest degree possible; and consider termination of LTOT in very extreme cases and in consultation with a multidisciplinary committee.”¹³

This statement is in contrast to the guidelines and policies of other countries, such as Sweden, where smoking is a direct contraindication for prescription of oxygen therapy, or in Australia and New Zealand, where the Thoracic Society of Australia and New Zealand oxygen therapy guidelines recommend against prescription of LTOT, citing “increased fire risk and the probability that the poorer prognosis conferred by smoking will offset treatment benefit.”^6,14

The prevalence of oxygen therapy introduces the potential for fire-related incidents with subsequent injury requiring medical care. There are few studies regarding home oxygen fire in the US due to the lack of a uniform reporting system. One study by Wendling and Pelletier analyzed deaths in Maine, Massachusetts, New Hampshire, and Oklahoma between 2000 and 2007 and found 38 deaths directly attributable to home oxygen fires as a result of smoking^.15 Further, the Consumer Product Safety Commission’s National Electronic Injury Surveillance System between 2003 and 2006 attributed 1,190 thermal burns related to home oxygen fires; the majority of which were ignited by tobacco smoking.¹⁵ The Swedish National Register of Respiratory Failure (Swedevox) published prospective population-based, consecutive cohort study that collected data over 17 years and evaluated the risk of fire-related incident in those on LTOT. Of the 12,497 patients sampled, 17 had a burn injury and 2 patients died. The low incidence of burn injury on LTOT was attributed to the strict guidelines instituted in Sweden for doctors to avoid prescribing LTOT to actively smoking patients.⁶ A follow-up study by Tanash and colleagues compared the risk of burn injury in each country, respectively. The results found an increased number of burn injuries in those on oxygen therapy in Denmark, a country with fewer restrictions on smoking compared with those of Sweden.⁷ Similarly, our results showed that the rate of fire and burn injuries was exclusively among veterans who were active smokers. All patients who were prescribed oxygen therapy at CTVHCS received counseling and signed Home Safety Agreements. Despite following the recommendations set forth by the VA on counseling, extensive harm reduction techniques, and close follow-up, we found there was still a high incidence of fires in veterans with COPD on LTOT who continue to smoke.

The findings from our study concur with those previously published regarding the risk of home oxygen fire and concomitant smoking, supporting the idea for more regulated and concrete guidelines for prescribing LTOT to those requiring it.⁸

Limitations

The major limitation was the small sample size of our study. Another limitation was that our study population is predominantly male as is common in veteran cohorts. In fiscal year 2016, the veteran population of Texas was 1,434,361 males and 168,967 females.¹⁶ According to Franklin and colleagues, HCPs noticed an increase use of long-term oxygen among women compared with that of men.¹⁷

Conclusions

Our study showed an increased odds of firerelated incidents of patients while on LTOT, strengthening the argument that even with extensive education, those who smoke and are on LTOT continue to put themselves at risk of a fire-related incident. This finding stresses the importance of continuing patient education on the importance of smoking cessation prior to administration of LTOT or avoiding fire hazards while on LTOT. Further research into LTOT and fire hazards could help in implementing a more structured approval process for patients who want to obtain LTOT. We propose further studies evaluating risk factors for the incidence of fire events among patients prescribed LTOT. A growing and aging population with a need for LTOT necessitates examination of oxygen safe prescribing.

Chronic obstructive pulmonary disease (COPD) has been the third leading cause of death in the US since 2008.¹ Current management of COPD includes smoking cessation, adequate nutrition, medication therapy, pulmonary rehabilitation, and vaccines.² Outside of pharmacologic management, oxygen therapy has become a staple treatment of chronic hypoxemic respiratory failure due to COPD. Landmark trials, including the Nocturnal Oxygen Therapy Trial (NOTT) and Medical Research Council (MRC) study, demonstrated improved survival in patients with COPD and hypoxemia, particularly if these patients received oxygen for 18 hours per day.^3,4 NOTT prospectively evaluated 203 patients at 6 centers who were randomly allocated to either continuous oxygen therapy or 12-hour nocturnal oxygen therapy. The overall mortality in the nocturnal oxygen therapy group was 1.94 times that in the continuous oxygen therapy group (P = .01).³ The MRC study included 87 patients who were randomized to oxygen therapy or no oxygen; risk of death was 12% per year in the treated group vs 29% per year in the control group (P = .04).⁴ The effectiveness of long-term oxygen therapy (LTOT) in active smokers continues to be a source of debate; although 50% of patients in the NOTT trial were smokers, there was no subgroup analysis of whether smoking status had an impact on survival in those on continuous oxygen therapy.

Although many therapies are available for the treatment of COPD, the most effective treatment to prevent the progression of COPD is smoking cessation. Resources like smoking cessation programs, nicotine patches, and medications, such as bupropion and varenicline, are available to aid smoking cessation.⁵ However, many patients are unable to quit tobacco use despite their best efforts using available resources, and they continue to smoke even with progressive COPD. Long-time smokers also are likely to continue smoking while on LTOT, which increases their risk for fire-related injury.^6-8

Traditional indications are being scrutinized after the LTOT trial found no benefit with respect to time to death or first hospitalization among patients with stable COPD and resting or exercise-induced moderate desaturation.⁹

Although oxygen accelerates combustion and is a potential fire hazard, LTOT has been prescribed even to active smokers as the 2 landmark trials did not exclude patients who were active smokers from receiving oxygen therapy.^3,4 Therefore, LTOT has traditionally been prescribed to veterans who are actively smoking, despite the fire hazard. Attempts at mitigating hazards related to oxygen therapy in active smokers include counseling extensively about safety measures (which includes avoiding open flames such as candles, large fires, or sparks when on LTOT and providing Home Safety Agreements—a written contract between prescriber and patient wherein the patient agrees to abide by the terms of the US Department of Veterans Affairs (VA) to mitigate hazards related to LTOT in order to receive LTOT (eAppendix 

Methods

With this practice in mind, we conducted an institutional review board approved retrospective chart review of all veterans with diagnosis of COPD within the Central Texas Veterans Health Care System (CTVHCS) who were prescribed new LTOT between October 1, 2010 and September 30, 2015. Given the retrospective nature of the chart review, patient consent was not obtained. Inclusion criteria were veterans aged > 18 years who had a confirmed diagnosis of COPD by spirometry and who met criteria for either continuous or ambulation- only oxygen therapy.

Criteria for exclusion included patients with hypoxemia not solely attributable to COPD or due to diseases other than COPD. We reviewed encounters in these patients’ charts, including follow-up in the clinic of the providers prescribing oxygen, to assess for fire-related incidents, defined as events wherein fire was visualized by the patient or by individuals living with the patient and with report provided to medical equipment company providing oxygen; the patient did not have to seek medical care to qualify for fire-related incident. Of the 158 patients who met the criteria for inclusion in the study, 152 were male.

Statistics

Bayesian logistic regression was used to model the outcome variable fire-related incident with the predictors smoking status, age, race, depression, PTSD, and type of oxygen used. Mental health disorders have significant effect on substance use disorders, such as alcohol use. Depression and PTSD were more common mental health diagnoses found in our patient population. Additionally, due to the small sample size, these psychiatric diagnoses were chosen to evaluate the impact of mental health disorders on firerelated events.

Although the sample size of events was small, weakly informative normal priors (0, 2.5) were used to shrink parameter estimates toward 0 and minimize overfitting. Weakly informative normal priors have also been suggested to deal with the problem of quasi-complete separation, where in our case, both smoking and no-PTSD perfectly predicted the 9 fire-related incidents.¹⁰ All input variables were centered and scaled as recommended. ⁹ The model fit well as assessed by posterior predictive checks, and Rhat was 1.00 for all parameters, indicating that all chains converged. Analysis was completed in R version 3.5.1 using the ‘brms’ package for Bayesian modeling.¹¹

Results

The mean age for the 158 included patients was 71.3 years in nonsmokers and 65.9 years in smokers. Fifty-three of the included patients were active smokers when LTOT was initiated. Nine veterans had fire-related incidents during the study period. All 9 patients were actively smoking (about 17%) at the time of the fire incidents. There were no deaths, and 5 patients required hospitalization due to facial burns resulting from the fire-related incidents. Our study focused on 5 baseline characteristics in our population (Table 1). After gathering data, our group inferred that these characteristics had a potential relationship to fire-related incidents compared with other variables that were studied. Future studies could look at other patient characteristics that may be linked to fire-related incidents in patients on LTOT. For example, not having PTSD also perfectly predicts fire-related incidents in our data (ie, none of the participants who had fire-related incidents had PTSD). Although this finding was not within the 95% confidence interval (CI) in the model, it does show that care must be taken when interpreting effects from small samples (Table 2). The modelestimated odds of a fire-related incident occurring in a smoker were 31.6 (5.1-372.7) times more likely than were the odds of a firerelated incident occurring in a nonsmoker, holding all other predictors at their reference level; 95% CI for the odds ratios for all other predictors in the model included a value of 1.

Discussion

This study showed evidence of increased odds of fire-related events in actively smoking patients receiving LTOT compared with patients who do not actively smoke while attempting to adjust for potential confounders. Of the 9 patients who had fire events, 5 required hospitalization for burns.

A similar retrospective cohort study by Sharma and colleagues in 2015 demonstrated an increased risk of burn-related injury when on LTOT but reiterated that the benefit of oxygen outweighs the risk of burn-related injury in patients requiring oxygen therapy.¹² Interestingly, Sharma and colleagues were unable to identify smoking status for the patients studied but further identified factors associated with burn injury to include male sex, low socioeconomic status, oxygen therapy use, and ≥ 3 comorbidities. The study’s conclusion recommended continued education by health care professionals (HCPs) to their patients on LTOT regarding potential for burn injury. In the same vein, the VA National Center for Ethics in Health Care noted that “clinicians should familiarize themselves with the risks and benefits of LTOT; should inform their patients of the risks and benefits without exaggerating the risk associated with smoking; avoid undue coercion inherent in the clinician’s ability to withdraw LTOT; reduce the risk to the greatest degree possible; and consider termination of LTOT in very extreme cases and in consultation with a multidisciplinary committee.”¹³

This statement is in contrast to the guidelines and policies of other countries, such as Sweden, where smoking is a direct contraindication for prescription of oxygen therapy, or in Australia and New Zealand, where the Thoracic Society of Australia and New Zealand oxygen therapy guidelines recommend against prescription of LTOT, citing “increased fire risk and the probability that the poorer prognosis conferred by smoking will offset treatment benefit.”^6,14

The prevalence of oxygen therapy introduces the potential for fire-related incidents with subsequent injury requiring medical care. There are few studies regarding home oxygen fire in the US due to the lack of a uniform reporting system. One study by Wendling and Pelletier analyzed deaths in Maine, Massachusetts, New Hampshire, and Oklahoma between 2000 and 2007 and found 38 deaths directly attributable to home oxygen fires as a result of smoking^.15 Further, the Consumer Product Safety Commission’s National Electronic Injury Surveillance System between 2003 and 2006 attributed 1,190 thermal burns related to home oxygen fires; the majority of which were ignited by tobacco smoking.¹⁵ The Swedish National Register of Respiratory Failure (Swedevox) published prospective population-based, consecutive cohort study that collected data over 17 years and evaluated the risk of fire-related incident in those on LTOT. Of the 12,497 patients sampled, 17 had a burn injury and 2 patients died. The low incidence of burn injury on LTOT was attributed to the strict guidelines instituted in Sweden for doctors to avoid prescribing LTOT to actively smoking patients.⁶ A follow-up study by Tanash and colleagues compared the risk of burn injury in each country, respectively. The results found an increased number of burn injuries in those on oxygen therapy in Denmark, a country with fewer restrictions on smoking compared with those of Sweden.⁷ Similarly, our results showed that the rate of fire and burn injuries was exclusively among veterans who were active smokers. All patients who were prescribed oxygen therapy at CTVHCS received counseling and signed Home Safety Agreements. Despite following the recommendations set forth by the VA on counseling, extensive harm reduction techniques, and close follow-up, we found there was still a high incidence of fires in veterans with COPD on LTOT who continue to smoke.

The findings from our study concur with those previously published regarding the risk of home oxygen fire and concomitant smoking, supporting the idea for more regulated and concrete guidelines for prescribing LTOT to those requiring it.⁸

Limitations

The major limitation was the small sample size of our study. Another limitation was that our study population is predominantly male as is common in veteran cohorts. In fiscal year 2016, the veteran population of Texas was 1,434,361 males and 168,967 females.¹⁶ According to Franklin and colleagues, HCPs noticed an increase use of long-term oxygen among women compared with that of men.¹⁷

Conclusions

Our study showed an increased odds of firerelated incidents of patients while on LTOT, strengthening the argument that even with extensive education, those who smoke and are on LTOT continue to put themselves at risk of a fire-related incident. This finding stresses the importance of continuing patient education on the importance of smoking cessation prior to administration of LTOT or avoiding fire hazards while on LTOT. Further research into LTOT and fire hazards could help in implementing a more structured approval process for patients who want to obtain LTOT. We propose further studies evaluating risk factors for the incidence of fire events among patients prescribed LTOT. A growing and aging population with a need for LTOT necessitates examination of oxygen safe prescribing.

Acalabrutinib, given alone or in combination with obinutuzumab, showed favorable progression-free survival (PFS) and overall survival (OS), compared with other frontline therapies for chronic lymphocytic leukemia (CLL) in fludarabine-ineligible patients, according to the results of a meta-analysis comparing clinical trial results.

Researchers conducted a systematic literature review for applicable CLL studies that examined frontline treatments in order to compare the results with data on acalabrutinib (monotherapy and in combination with obinutuzumab) from patients in the ELEVATE-TN study (NCT02475681), according to a report published in Clinical Therapeutics.

Matthew S. Davids, MD, MMSc, of the Dana-Farber Cancer Institute in Boston, and colleagues performed a network meta-analysis (NMA) comparing acalabrutinib versus other standard frontline therapies for CLL in patients for whom fludarabine-based treatment is not appropriate.

“In the absence of head-to-head trial data, NMAs allow for simultaneous comparisons of a number of interventions with multiple comparators, by synthesizing direct and indirect evidence,” the authors stated.

Eight randomized controlled trials (RCTs) met the criteria for comparison.

The researchers constructed two evidence networks: Network A comprised solely RCTs that met the inclusion criteria, and Network B comprised seven RCTs and a published cross-trial comparison of ibrutinib from RESONATE-2 and chlorambucil plus obinutuzumab from iLLUMINATE. PFS and OS results were reported by using hazard ratios and 95% credible intervals.


 

Overall benefit

Both networks showed a significant improvement in PFS for acalabrutinib plus obinutuzumab over all comparators, according to the researchers. Both networks also showed a significant improvement in PFS for acalabrutinib monotherapy versus most comparators, with a significant difference to ibrutinib monotherapy found in Network A but not Network B.

Conversely, a significant difference in PFS was observed for acalabrutinib monotherapy versus venetoclax plus obinutuzumab in Network B but not Network A.

Overall survival hazard ratios ranged from 0.18 to 0.65 in favor of acalabrutinib-based treatment, but not all were significant. Acalabrutinib plus obinutuzumab ranked highest in terms of PFS and OS improvement, followed by acalabrutinib monotherapy.

“Although our NMAs provide useful insights into the relative efficacy of acalabrutinib, compared with other frontline treatments of CLL, the results cannot be considered confirmatory, and head-to-head randomized trials are needed, especially to compare the efficacy of acalabrutinib versus other targeted agents,” the researchers concluded.

AstraZeneca sponsored the study. The authors reported funding from AstraZeneca and numerous other pharmaceutical companies.

[email protected]

SOURCE: Davids MS et al. Clin Ther. 2020 Oct 5. doi: 10.1016/j.clinthera.2020.08.017.

Acalabrutinib, given alone or in combination with obinutuzumab, showed favorable progression-free survival (PFS) and overall survival (OS), compared with other frontline therapies for chronic lymphocytic leukemia (CLL) in fludarabine-ineligible patients, according to the results of a meta-analysis comparing clinical trial results.

Researchers conducted a systematic literature review for applicable CLL studies that examined frontline treatments in order to compare the results with data on acalabrutinib (monotherapy and in combination with obinutuzumab) from patients in the ELEVATE-TN study (NCT02475681), according to a report published in Clinical Therapeutics.

Matthew S. Davids, MD, MMSc, of the Dana-Farber Cancer Institute in Boston, and colleagues performed a network meta-analysis (NMA) comparing acalabrutinib versus other standard frontline therapies for CLL in patients for whom fludarabine-based treatment is not appropriate.

“In the absence of head-to-head trial data, NMAs allow for simultaneous comparisons of a number of interventions with multiple comparators, by synthesizing direct and indirect evidence,” the authors stated.

Eight randomized controlled trials (RCTs) met the criteria for comparison.

The researchers constructed two evidence networks: Network A comprised solely RCTs that met the inclusion criteria, and Network B comprised seven RCTs and a published cross-trial comparison of ibrutinib from RESONATE-2 and chlorambucil plus obinutuzumab from iLLUMINATE. PFS and OS results were reported by using hazard ratios and 95% credible intervals.


 

Overall benefit

Both networks showed a significant improvement in PFS for acalabrutinib plus obinutuzumab over all comparators, according to the researchers. Both networks also showed a significant improvement in PFS for acalabrutinib monotherapy versus most comparators, with a significant difference to ibrutinib monotherapy found in Network A but not Network B.

Conversely, a significant difference in PFS was observed for acalabrutinib monotherapy versus venetoclax plus obinutuzumab in Network B but not Network A.

Overall survival hazard ratios ranged from 0.18 to 0.65 in favor of acalabrutinib-based treatment, but not all were significant. Acalabrutinib plus obinutuzumab ranked highest in terms of PFS and OS improvement, followed by acalabrutinib monotherapy.

“Although our NMAs provide useful insights into the relative efficacy of acalabrutinib, compared with other frontline treatments of CLL, the results cannot be considered confirmatory, and head-to-head randomized trials are needed, especially to compare the efficacy of acalabrutinib versus other targeted agents,” the researchers concluded.

AstraZeneca sponsored the study. The authors reported funding from AstraZeneca and numerous other pharmaceutical companies.

[email protected]

SOURCE: Davids MS et al. Clin Ther. 2020 Oct 5. doi: 10.1016/j.clinthera.2020.08.017.

Acalabrutinib, given alone or in combination with obinutuzumab, showed favorable progression-free survival (PFS) and overall survival (OS), compared with other frontline therapies for chronic lymphocytic leukemia (CLL) in fludarabine-ineligible patients, according to the results of a meta-analysis comparing clinical trial results.

Researchers conducted a systematic literature review for applicable CLL studies that examined frontline treatments in order to compare the results with data on acalabrutinib (monotherapy and in combination with obinutuzumab) from patients in the ELEVATE-TN study (NCT02475681), according to a report published in Clinical Therapeutics.

Matthew S. Davids, MD, MMSc, of the Dana-Farber Cancer Institute in Boston, and colleagues performed a network meta-analysis (NMA) comparing acalabrutinib versus other standard frontline therapies for CLL in patients for whom fludarabine-based treatment is not appropriate.

“In the absence of head-to-head trial data, NMAs allow for simultaneous comparisons of a number of interventions with multiple comparators, by synthesizing direct and indirect evidence,” the authors stated.

Eight randomized controlled trials (RCTs) met the criteria for comparison.

The researchers constructed two evidence networks: Network A comprised solely RCTs that met the inclusion criteria, and Network B comprised seven RCTs and a published cross-trial comparison of ibrutinib from RESONATE-2 and chlorambucil plus obinutuzumab from iLLUMINATE. PFS and OS results were reported by using hazard ratios and 95% credible intervals.


 

Overall benefit

Both networks showed a significant improvement in PFS for acalabrutinib plus obinutuzumab over all comparators, according to the researchers. Both networks also showed a significant improvement in PFS for acalabrutinib monotherapy versus most comparators, with a significant difference to ibrutinib monotherapy found in Network A but not Network B.

Conversely, a significant difference in PFS was observed for acalabrutinib monotherapy versus venetoclax plus obinutuzumab in Network B but not Network A.

Overall survival hazard ratios ranged from 0.18 to 0.65 in favor of acalabrutinib-based treatment, but not all were significant. Acalabrutinib plus obinutuzumab ranked highest in terms of PFS and OS improvement, followed by acalabrutinib monotherapy.

“Although our NMAs provide useful insights into the relative efficacy of acalabrutinib, compared with other frontline treatments of CLL, the results cannot be considered confirmatory, and head-to-head randomized trials are needed, especially to compare the efficacy of acalabrutinib versus other targeted agents,” the researchers concluded.

AstraZeneca sponsored the study. The authors reported funding from AstraZeneca and numerous other pharmaceutical companies.

[email protected]

SOURCE: Davids MS et al. Clin Ther. 2020 Oct 5. doi: 10.1016/j.clinthera.2020.08.017.

International normalized ratio (INR) does not predict periprocedural bleeding in patients with cirrhosis, according to a meta-analysis of 29 studies.

This finding should deter the common practice of delivering blood products to cirrhotic patients with an elevated INR, reported lead author Alexander J. Kovalic, MD, of Novant Forsyth Medical Center in Winston Salem, N.C., and colleagues.

“INR measurement among cirrhotic patients is important in MELD [Model for End-Stage Liver Disease] prognostication and assessment of underlying hepatic synthetic function, however the INR alone does not capture the complicated interplay of anticoagulant and procoagulant deficiencies present in cirrhotic coagulopathy,” Dr. Kovalic and colleagues wrote in Alimentary Pharmacology & Therapeutics. “Yet, the ‘correction’ of these aberrancies among peripheral coagulation tests remains common ... even in modern practice, and not uncommonly occurs in the periprocedural setting.”

According to investigators, addressing INR with blood transfusion can have a litany of negative effects. Beyond the risks faced by all patient populations, increasing blood volume in those with cirrhosis can increase portal venous pressure, thereby raising risks of portal gastropathy or variceal hemorrhage. In addition, giving plasma products to patients with cirrhotic coagulopathy may further disrupt the balance between anticoagulants and procoagulants, potentially triggering disseminated intravascular coagulation.

Dr. Kovalic and colleagues noted that the lack of correlation between peripheral coagulation tests and bleeding risk has been a longstanding subject of investigation, citing studies from as early as 1981.

To add further weight to this body of evidence, the investigators conducted a systematic review and meta-analysis involving 13,276 patients with cirrhosis who underwent various procedures between 1999 and 2019. Primary outcomes included periprocedural bleeding events and the association between preprocedural INR and periprocedural bleeding events. Secondary outcomes included mortality, quantity of blood and/or plasma products used, and relationship between preprocedural platelet count and periprocedural bleeding events.

The analysis showed that preprocedural INR was not significantly associated with periprocedural bleeding events (pooled odds ratio, 1.52; 95% confidence interval, 0.99-2.33; P = .06), a finding that held across INR threshold subgroups. Similarly, no significant difference was found between mean INR of patients who had bleeding events versus that of those who did not (pooled mean difference, 0.05; 95% CI, 0.03-0.13; P = .23).

Preprocedural platelet count was also a poor predictor of periprocedural bleeding, with a pooled odds ratio of 1.24 (95% CI, 0.55-2.77; P = .60), although the investigators noted that platelet count thresholds varied widely across studies, from 30 to 150 × 10⁹/L. When studies were stratified by procedural bleeding risk or procedure type, subgroup effects were no longer significant. Other secondary endpoints were incalculable because of insufficient data.

“Hopefully, these findings will spark initiation of more large-scale, higher-quality studies ... to reinforce minimizing administration of fresh frozen plasma for inappropriate correction of INR, which carries a multitude of adverse effects among cirrhotic [patients],” the investigators concluded.

According to Stephen H. Caldwell, MD, of the University of Virginia in Charlottesville, “The present paper augments accumulating literature over the past 15 years that INR should be discarded as a measure of procedure-related bleeding risk.”

Dr. Caldwell pointed out that “bleeding in cirrhosis is usually related to portal hypertension not with impaired hemostasis, with the occasional exception of hyperfibrinolysis, which is very different from a prolonged INR.”

He went on to suggest that the present findings should dissuade clinicians from a practice that, for some, is reflexive rather than evidence based.

“It’s remarkable how many medical practices become entrenched based on hand-me-down teaching during our early training years, and remain so for many years beyond as we disperse into various medical and surgical fields,” Dr. Caldwell said. “These learned approaches to common problems can clearly persist for generations despite overwhelming evidence to the contrary that usually evolve slowly and well-insulated within subspecialties or sub-subspecialties, and hence take several generations of training to diffuse into the wider practice of medical care for common problems. These may become matters of expedience in decision-making, much like the old antibiotic conundrum of ‘no-think-a-cillin,’ as critics referred to over-use of broad spectrum antibiotics. And so it has been with the INR.”The investigators disclosed relationships with AbbVie, Eisai, Gilead, and others. Dr. Caldwell disclosed research support from Daiichi concerning the potential role of anticoagulation therapy in preventing cirrhosis progression.

SOURCE: Kovalic AJ et al. Aliment Pharmacol Ther. 2020 Sep 10. doi: 10.1111/apt.16078.

International normalized ratio (INR) does not predict periprocedural bleeding in patients with cirrhosis, according to a meta-analysis of 29 studies.

This finding should deter the common practice of delivering blood products to cirrhotic patients with an elevated INR, reported lead author Alexander J. Kovalic, MD, of Novant Forsyth Medical Center in Winston Salem, N.C., and colleagues.

“INR measurement among cirrhotic patients is important in MELD [Model for End-Stage Liver Disease] prognostication and assessment of underlying hepatic synthetic function, however the INR alone does not capture the complicated interplay of anticoagulant and procoagulant deficiencies present in cirrhotic coagulopathy,” Dr. Kovalic and colleagues wrote in Alimentary Pharmacology & Therapeutics. “Yet, the ‘correction’ of these aberrancies among peripheral coagulation tests remains common ... even in modern practice, and not uncommonly occurs in the periprocedural setting.”

According to investigators, addressing INR with blood transfusion can have a litany of negative effects. Beyond the risks faced by all patient populations, increasing blood volume in those with cirrhosis can increase portal venous pressure, thereby raising risks of portal gastropathy or variceal hemorrhage. In addition, giving plasma products to patients with cirrhotic coagulopathy may further disrupt the balance between anticoagulants and procoagulants, potentially triggering disseminated intravascular coagulation.

Dr. Kovalic and colleagues noted that the lack of correlation between peripheral coagulation tests and bleeding risk has been a longstanding subject of investigation, citing studies from as early as 1981.

To add further weight to this body of evidence, the investigators conducted a systematic review and meta-analysis involving 13,276 patients with cirrhosis who underwent various procedures between 1999 and 2019. Primary outcomes included periprocedural bleeding events and the association between preprocedural INR and periprocedural bleeding events. Secondary outcomes included mortality, quantity of blood and/or plasma products used, and relationship between preprocedural platelet count and periprocedural bleeding events.

The analysis showed that preprocedural INR was not significantly associated with periprocedural bleeding events (pooled odds ratio, 1.52; 95% confidence interval, 0.99-2.33; P = .06), a finding that held across INR threshold subgroups. Similarly, no significant difference was found between mean INR of patients who had bleeding events versus that of those who did not (pooled mean difference, 0.05; 95% CI, 0.03-0.13; P = .23).

Preprocedural platelet count was also a poor predictor of periprocedural bleeding, with a pooled odds ratio of 1.24 (95% CI, 0.55-2.77; P = .60), although the investigators noted that platelet count thresholds varied widely across studies, from 30 to 150 × 10⁹/L. When studies were stratified by procedural bleeding risk or procedure type, subgroup effects were no longer significant. Other secondary endpoints were incalculable because of insufficient data.

“Hopefully, these findings will spark initiation of more large-scale, higher-quality studies ... to reinforce minimizing administration of fresh frozen plasma for inappropriate correction of INR, which carries a multitude of adverse effects among cirrhotic [patients],” the investigators concluded.

According to Stephen H. Caldwell, MD, of the University of Virginia in Charlottesville, “The present paper augments accumulating literature over the past 15 years that INR should be discarded as a measure of procedure-related bleeding risk.”

Dr. Caldwell pointed out that “bleeding in cirrhosis is usually related to portal hypertension not with impaired hemostasis, with the occasional exception of hyperfibrinolysis, which is very different from a prolonged INR.”

He went on to suggest that the present findings should dissuade clinicians from a practice that, for some, is reflexive rather than evidence based.

“It’s remarkable how many medical practices become entrenched based on hand-me-down teaching during our early training years, and remain so for many years beyond as we disperse into various medical and surgical fields,” Dr. Caldwell said. “These learned approaches to common problems can clearly persist for generations despite overwhelming evidence to the contrary that usually evolve slowly and well-insulated within subspecialties or sub-subspecialties, and hence take several generations of training to diffuse into the wider practice of medical care for common problems. These may become matters of expedience in decision-making, much like the old antibiotic conundrum of ‘no-think-a-cillin,’ as critics referred to over-use of broad spectrum antibiotics. And so it has been with the INR.”The investigators disclosed relationships with AbbVie, Eisai, Gilead, and others. Dr. Caldwell disclosed research support from Daiichi concerning the potential role of anticoagulation therapy in preventing cirrhosis progression.

SOURCE: Kovalic AJ et al. Aliment Pharmacol Ther. 2020 Sep 10. doi: 10.1111/apt.16078.

International normalized ratio (INR) does not predict periprocedural bleeding in patients with cirrhosis, according to a meta-analysis of 29 studies.

This finding should deter the common practice of delivering blood products to cirrhotic patients with an elevated INR, reported lead author Alexander J. Kovalic, MD, of Novant Forsyth Medical Center in Winston Salem, N.C., and colleagues.

“INR measurement among cirrhotic patients is important in MELD [Model for End-Stage Liver Disease] prognostication and assessment of underlying hepatic synthetic function, however the INR alone does not capture the complicated interplay of anticoagulant and procoagulant deficiencies present in cirrhotic coagulopathy,” Dr. Kovalic and colleagues wrote in Alimentary Pharmacology & Therapeutics. “Yet, the ‘correction’ of these aberrancies among peripheral coagulation tests remains common ... even in modern practice, and not uncommonly occurs in the periprocedural setting.”

According to investigators, addressing INR with blood transfusion can have a litany of negative effects. Beyond the risks faced by all patient populations, increasing blood volume in those with cirrhosis can increase portal venous pressure, thereby raising risks of portal gastropathy or variceal hemorrhage. In addition, giving plasma products to patients with cirrhotic coagulopathy may further disrupt the balance between anticoagulants and procoagulants, potentially triggering disseminated intravascular coagulation.

Dr. Kovalic and colleagues noted that the lack of correlation between peripheral coagulation tests and bleeding risk has been a longstanding subject of investigation, citing studies from as early as 1981.

To add further weight to this body of evidence, the investigators conducted a systematic review and meta-analysis involving 13,276 patients with cirrhosis who underwent various procedures between 1999 and 2019. Primary outcomes included periprocedural bleeding events and the association between preprocedural INR and periprocedural bleeding events. Secondary outcomes included mortality, quantity of blood and/or plasma products used, and relationship between preprocedural platelet count and periprocedural bleeding events.

The analysis showed that preprocedural INR was not significantly associated with periprocedural bleeding events (pooled odds ratio, 1.52; 95% confidence interval, 0.99-2.33; P = .06), a finding that held across INR threshold subgroups. Similarly, no significant difference was found between mean INR of patients who had bleeding events versus that of those who did not (pooled mean difference, 0.05; 95% CI, 0.03-0.13; P = .23).

Preprocedural platelet count was also a poor predictor of periprocedural bleeding, with a pooled odds ratio of 1.24 (95% CI, 0.55-2.77; P = .60), although the investigators noted that platelet count thresholds varied widely across studies, from 30 to 150 × 10⁹/L. When studies were stratified by procedural bleeding risk or procedure type, subgroup effects were no longer significant. Other secondary endpoints were incalculable because of insufficient data.

“Hopefully, these findings will spark initiation of more large-scale, higher-quality studies ... to reinforce minimizing administration of fresh frozen plasma for inappropriate correction of INR, which carries a multitude of adverse effects among cirrhotic [patients],” the investigators concluded.

According to Stephen H. Caldwell, MD, of the University of Virginia in Charlottesville, “The present paper augments accumulating literature over the past 15 years that INR should be discarded as a measure of procedure-related bleeding risk.”

Dr. Caldwell pointed out that “bleeding in cirrhosis is usually related to portal hypertension not with impaired hemostasis, with the occasional exception of hyperfibrinolysis, which is very different from a prolonged INR.”

He went on to suggest that the present findings should dissuade clinicians from a practice that, for some, is reflexive rather than evidence based.

“It’s remarkable how many medical practices become entrenched based on hand-me-down teaching during our early training years, and remain so for many years beyond as we disperse into various medical and surgical fields,” Dr. Caldwell said. “These learned approaches to common problems can clearly persist for generations despite overwhelming evidence to the contrary that usually evolve slowly and well-insulated within subspecialties or sub-subspecialties, and hence take several generations of training to diffuse into the wider practice of medical care for common problems. These may become matters of expedience in decision-making, much like the old antibiotic conundrum of ‘no-think-a-cillin,’ as critics referred to over-use of broad spectrum antibiotics. And so it has been with the INR.”The investigators disclosed relationships with AbbVie, Eisai, Gilead, and others. Dr. Caldwell disclosed research support from Daiichi concerning the potential role of anticoagulation therapy in preventing cirrhosis progression.

SOURCE: Kovalic AJ et al. Aliment Pharmacol Ther. 2020 Sep 10. doi: 10.1111/apt.16078.

Regular use of proton pump inhibitors (PPIs) is associated with an increased risk of type 2 diabetes, according to a large prospective analysis of the Nurses’ Health Study. The results follow on other studies suggesting other potential adverse effects of PPIs such as dementia, kidney damage, and micronutrient deficiencies.

The authors, led by Jinqiu Yuan and Changhua Zhang of Sun Yat-sen University (Guangdong, China), call for regular blood glucose testing and diabetes screening for patients on long-term PPIs. But not all are convinced. “I think that’s a strong recommendation from the available data and it’s unclear how that would be put into practice. I think instead practitioners should adhere to best practices, which emphasize using the lowest effective dose of PPIs for patients with appropriate indications,” David Leiman, MD, MSHP, assistant professor of medicine at Duke University, Durham, N.C. said in an interview.

“Overall, the data from the study can be classified as provocative results that I think may warrant further study,” he added. Randomized, controlled trials or many more observational studies would be required to establish causality between PPI use and diabetes risk, and in any case the findings of the current study don’t warrant a change in practice, Dr. Leiman said, noting that the study’s design makes it likely that much or all of the observed associations were due to confounding.

The study appeared online Sept. 28 in Gut.

The researchers analyzed data from 80,500 women from the Nurses’ Health Study, 95,550 women from the Nurses’ Health Study II, and 28,639 men from the Health Professionals Follow-up Study (HPFS), with a median follow-up time of 12 years in NHS and NHS2 and 9.8 years in HPFS.

The absolute risk of diabetes was 7.44 per 1,000 person-years in PPI users versus 4.32 among nonusers. After adjustment for lagging PPI use for 2 years and stratification by age and study period, PPI use was associated with a 74% increased risk of diabetes (hazard ratio , 1.74; 95% confidence interval, 1.37-2.20). Multivariable adjustment for demographic factors, lifestyle habits, comorbidities, and use of other medications and clinical indications for PPI use attenuated the association but did not eliminate it (HR, 1.24; 95% CI, 1.17-1.31).

There was no statistically significant association in the HPFS group (HR, 1.12; 95% CI, 0.91-1.38), possibly because of the smaller sample size.

At 1 year, the number needed to harm with PPIs was 318.9 (95% CI, 285.2-385.0). At 2 years it was 170.8 (95% CI, 150.8-209.7) and at 3 years it was 77.3 (95% CI, 66.8-97.0).

At 0-2 years, PPI use was associated with a 5% increase in diabetes risk (HR, 1.05; 95% CI, 0.93-1.19). More than 2 years of use was associated with higher risk (HR, 1.26; 95% CI, 1.18-1.35).

There was also an association between stopping PPI use and a decreased risk of diabetes: Compared with current PPI users, those who had stopped within the past 2 years had a 17% reduction in risk (HR, 0.83; 95% CI, 0.70-0.98), and those who had stopped more than 2 years previously had a 19% reduction (HR, 0.81; 95% CI, 0.76-0.86).

The researchers also examined diabetes risk associated with use of H₂ receptor agonists (H₂RAs), since the drugs share clinical indications with PPIs. H₂RA use was also associated with a higher risk of diabetes (adjusted HR, 1.14; 95% CI, 1.07-1.23).

The researchers suggested that the fact that the less potent H₂RA inhibitors had a less pronounced association with diabetes risk supports the idea that acid suppression may be related to diabetes pathogenesis.

The authors also suggest that changes to the gut microbiota may underlie increased risk. PPI use has been shown to reduce gut microbiome diversity and alter its phenotype. Such changes could lead to weight gain, metabolic syndrome, and chronic liver disease, which could in turn heighten risk.

The study is limited by its observational nature, and lacked detailed information on dosage, frequency, and indications for PPI use.

SOURCE: Yuan J et al. Gut. 2020 Sep 28. doi: 10.1136/gutjnl-2020-322557.

Regular use of proton pump inhibitors (PPIs) is associated with an increased risk of type 2 diabetes, according to a large prospective analysis of the Nurses’ Health Study. The results follow on other studies suggesting other potential adverse effects of PPIs such as dementia, kidney damage, and micronutrient deficiencies.

The authors, led by Jinqiu Yuan and Changhua Zhang of Sun Yat-sen University (Guangdong, China), call for regular blood glucose testing and diabetes screening for patients on long-term PPIs. But not all are convinced. “I think that’s a strong recommendation from the available data and it’s unclear how that would be put into practice. I think instead practitioners should adhere to best practices, which emphasize using the lowest effective dose of PPIs for patients with appropriate indications,” David Leiman, MD, MSHP, assistant professor of medicine at Duke University, Durham, N.C. said in an interview.

“Overall, the data from the study can be classified as provocative results that I think may warrant further study,” he added. Randomized, controlled trials or many more observational studies would be required to establish causality between PPI use and diabetes risk, and in any case the findings of the current study don’t warrant a change in practice, Dr. Leiman said, noting that the study’s design makes it likely that much or all of the observed associations were due to confounding.

The study appeared online Sept. 28 in Gut.

The researchers analyzed data from 80,500 women from the Nurses’ Health Study, 95,550 women from the Nurses’ Health Study II, and 28,639 men from the Health Professionals Follow-up Study (HPFS), with a median follow-up time of 12 years in NHS and NHS2 and 9.8 years in HPFS.

The absolute risk of diabetes was 7.44 per 1,000 person-years in PPI users versus 4.32 among nonusers. After adjustment for lagging PPI use for 2 years and stratification by age and study period, PPI use was associated with a 74% increased risk of diabetes (hazard ratio , 1.74; 95% confidence interval, 1.37-2.20). Multivariable adjustment for demographic factors, lifestyle habits, comorbidities, and use of other medications and clinical indications for PPI use attenuated the association but did not eliminate it (HR, 1.24; 95% CI, 1.17-1.31).

There was no statistically significant association in the HPFS group (HR, 1.12; 95% CI, 0.91-1.38), possibly because of the smaller sample size.

At 1 year, the number needed to harm with PPIs was 318.9 (95% CI, 285.2-385.0). At 2 years it was 170.8 (95% CI, 150.8-209.7) and at 3 years it was 77.3 (95% CI, 66.8-97.0).

At 0-2 years, PPI use was associated with a 5% increase in diabetes risk (HR, 1.05; 95% CI, 0.93-1.19). More than 2 years of use was associated with higher risk (HR, 1.26; 95% CI, 1.18-1.35).

There was also an association between stopping PPI use and a decreased risk of diabetes: Compared with current PPI users, those who had stopped within the past 2 years had a 17% reduction in risk (HR, 0.83; 95% CI, 0.70-0.98), and those who had stopped more than 2 years previously had a 19% reduction (HR, 0.81; 95% CI, 0.76-0.86).

The researchers also examined diabetes risk associated with use of H₂ receptor agonists (H₂RAs), since the drugs share clinical indications with PPIs. H₂RA use was also associated with a higher risk of diabetes (adjusted HR, 1.14; 95% CI, 1.07-1.23).

The researchers suggested that the fact that the less potent H₂RA inhibitors had a less pronounced association with diabetes risk supports the idea that acid suppression may be related to diabetes pathogenesis.

The authors also suggest that changes to the gut microbiota may underlie increased risk. PPI use has been shown to reduce gut microbiome diversity and alter its phenotype. Such changes could lead to weight gain, metabolic syndrome, and chronic liver disease, which could in turn heighten risk.

The study is limited by its observational nature, and lacked detailed information on dosage, frequency, and indications for PPI use.

SOURCE: Yuan J et al. Gut. 2020 Sep 28. doi: 10.1136/gutjnl-2020-322557.

Regular use of proton pump inhibitors (PPIs) is associated with an increased risk of type 2 diabetes, according to a large prospective analysis of the Nurses’ Health Study. The results follow on other studies suggesting other potential adverse effects of PPIs such as dementia, kidney damage, and micronutrient deficiencies.

The authors, led by Jinqiu Yuan and Changhua Zhang of Sun Yat-sen University (Guangdong, China), call for regular blood glucose testing and diabetes screening for patients on long-term PPIs. But not all are convinced. “I think that’s a strong recommendation from the available data and it’s unclear how that would be put into practice. I think instead practitioners should adhere to best practices, which emphasize using the lowest effective dose of PPIs for patients with appropriate indications,” David Leiman, MD, MSHP, assistant professor of medicine at Duke University, Durham, N.C. said in an interview.

“Overall, the data from the study can be classified as provocative results that I think may warrant further study,” he added. Randomized, controlled trials or many more observational studies would be required to establish causality between PPI use and diabetes risk, and in any case the findings of the current study don’t warrant a change in practice, Dr. Leiman said, noting that the study’s design makes it likely that much or all of the observed associations were due to confounding.

The study appeared online Sept. 28 in Gut.

The researchers analyzed data from 80,500 women from the Nurses’ Health Study, 95,550 women from the Nurses’ Health Study II, and 28,639 men from the Health Professionals Follow-up Study (HPFS), with a median follow-up time of 12 years in NHS and NHS2 and 9.8 years in HPFS.

The absolute risk of diabetes was 7.44 per 1,000 person-years in PPI users versus 4.32 among nonusers. After adjustment for lagging PPI use for 2 years and stratification by age and study period, PPI use was associated with a 74% increased risk of diabetes (hazard ratio , 1.74; 95% confidence interval, 1.37-2.20). Multivariable adjustment for demographic factors, lifestyle habits, comorbidities, and use of other medications and clinical indications for PPI use attenuated the association but did not eliminate it (HR, 1.24; 95% CI, 1.17-1.31).

There was no statistically significant association in the HPFS group (HR, 1.12; 95% CI, 0.91-1.38), possibly because of the smaller sample size.

At 1 year, the number needed to harm with PPIs was 318.9 (95% CI, 285.2-385.0). At 2 years it was 170.8 (95% CI, 150.8-209.7) and at 3 years it was 77.3 (95% CI, 66.8-97.0).

At 0-2 years, PPI use was associated with a 5% increase in diabetes risk (HR, 1.05; 95% CI, 0.93-1.19). More than 2 years of use was associated with higher risk (HR, 1.26; 95% CI, 1.18-1.35).

There was also an association between stopping PPI use and a decreased risk of diabetes: Compared with current PPI users, those who had stopped within the past 2 years had a 17% reduction in risk (HR, 0.83; 95% CI, 0.70-0.98), and those who had stopped more than 2 years previously had a 19% reduction (HR, 0.81; 95% CI, 0.76-0.86).

The researchers also examined diabetes risk associated with use of H₂ receptor agonists (H₂RAs), since the drugs share clinical indications with PPIs. H₂RA use was also associated with a higher risk of diabetes (adjusted HR, 1.14; 95% CI, 1.07-1.23).

The researchers suggested that the fact that the less potent H₂RA inhibitors had a less pronounced association with diabetes risk supports the idea that acid suppression may be related to diabetes pathogenesis.

The authors also suggest that changes to the gut microbiota may underlie increased risk. PPI use has been shown to reduce gut microbiome diversity and alter its phenotype. Such changes could lead to weight gain, metabolic syndrome, and chronic liver disease, which could in turn heighten risk.

The study is limited by its observational nature, and lacked detailed information on dosage, frequency, and indications for PPI use.

SOURCE: Yuan J et al. Gut. 2020 Sep 28. doi: 10.1136/gutjnl-2020-322557.

Latino patients participating in clinical trials of psoriasis treatments were found to have different patterns of disease and a lower level of quality of life, compared with White participants in the same studies, according to new data presented at the virtual Skin of Color Update 2020.

“Our findings demonstrate that, though White psoriasis patients may have higher severity in certain body regions such as the trunk, axilla, and groin areas, Latino psoriasis patients have a greater distribution of involvement, particularly in their upper limbs,” reported Alyssa G. Ashbaugh, a third-year medical student at the University of California, Irvine.

The study also found that psoriasis had a greater adverse impact on well-being, as measured with the Dermatology Life Quality Index (DLQI). At entry into the trials from which these patients were drawn, the higher DLQI score, significantly lower quality of life, was nearly two times higher (13.78 vs. 7.31; P = .01) among the Latino patients, compared with White patients.

This is not the first study to show a greater negative impact from psoriasis on Latinos than Whites, according to Ms. Ashbaugh. For example, Latinos had the worse quality of life at baseline by DLQI score than White, Asians, or Black participants in a trial of etanercept that enrolled more than 2000 patients.

In this retrospective chart review, patient characteristics were evaluated in all 21 Latino patients enrolled in psoriasis clinical trials at the University of California, Irvine, in a recent period. They were matched by age and gender to an equal number of White patients participating in the same trials.

The mean age at diagnosis of psoriasis was older in the Latino group than in the White population (42.4 vs. 35.6 years; P = .20), but the difference did not reach statistical significance. The proportion of patients with severe disease on investigator global assessment was also greater but not significantly different in the Latino group, compared with the White group, respectively (42.9% vs. 28.6%; P = .10).

However, differences in the patterns of disease did reach significance. This included a lower mean Psoriasis Assessment Severity Index score of the trunk, axilla, and groin in Latinos (4.74 vs. 9.73; P = .02). But compared with White participants, Latinos had a higher mean percentage of body surface area involvement in the upper limbs (4.78 vs. 1.85; P = .004) and a higher percentage of total body surface area involvement (20.50 vs. 10.03; P = .02).

“While White patients were found to have lived many more years with psoriasis, it is important for future studies to examine whether this is due to earlier onset or delayed diagnosis, given the fact that minorities are less likely to have access to a dermatologist,” reported Ms. Ashbaugh, who performed this work under the guidance of the senior author, Natasha Mesinkovska, MD, PhD, with the department of dermatology, University of California, Irvine.

Overall, the study suggested that body surface coverage and severity is not similarly distributed in Latinos relative to Whites. Although Ms. Ashbaugh conceded that the small sample size and retrospective design of this study are important limitations, she believes that her study, along with previously published studies that suggest psoriasis characteristics may differ meaningfully by race or ethnicity, raises issues that should be explored in future studies designed to confirm differences and whether those differences should affect management.

Other studies have suggested “there are notable differences in the presentation of psoriasis between racial and ethnic groups with the Latino population often presenting to physicians with more severe psoriasis and increased body surface area involvement,” Ms. Ashbaugh noted. Although this appears to be one of the first studies to examine psoriasis characteristics in Latinos relative to Whites, she believes this is an area ripe for further analysis.

Psoriasis “is not a rare occurrence” in non-White populations even if U.S. data suggest that the prevalence in “people of color is lower than that of psoriasis in the U.S. white population,” Amy McMichael, MD, chair of the department of dermatology, Wake Forest Baptist Medical Center, Winston-Salem, N.C., commented in an interview after the meeting. She agreed that it cannot be assumed that psoriasis in skin of color has the same manifestations or responds to treatment in the same way as in White patients.

“Studies have suggested that lesion thickness and, often, extent of disease can be worse in patients of color. Few studies to date have examined the efficacy of treatments and impact of disease in these populations,” she said.

One exception was a study Dr. McMichael and colleagues published last year on the efficacy and safety of the interleukin-17 receptor A antagonist brodalumab for psoriasis in patients of color. The study showed that Black, Latino, and Asian patients participating in the AMAGINE-2 and AMAGINE-3 trials achieved similar outcomes as White participants.

“We published this study because this is one of the first, if not the first, to have enough patients of color to actually draw conclusions about the efficacy of the biologic as well as the patient-reported outcomes,” she explained.

Like the author of the evaluation of Latino patients undertaken at the University of California, Irvine, Dr. McMichael said studies of psoriasis specific to patients of color are needed.

“We cannot assume all patients of color will have the same outcomes as their Caucasian counterparts. It is imperative to include those of color in future psoriasis treatment trials in order to determine the efficacy of new medications,” she added, specifically calling for collection of data on patient-reported outcomes.

Ms. Ashbaugh has no relevant financial relationships to disclose. Dr. McMichael’s disclosures included serving as an investigator and/or consultant for companies that included Allergan, Procter & Gamble, Johnson & Johnson, and Aclaris.

Latino patients participating in clinical trials of psoriasis treatments were found to have different patterns of disease and a lower level of quality of life, compared with White participants in the same studies, according to new data presented at the virtual Skin of Color Update 2020.

“Our findings demonstrate that, though White psoriasis patients may have higher severity in certain body regions such as the trunk, axilla, and groin areas, Latino psoriasis patients have a greater distribution of involvement, particularly in their upper limbs,” reported Alyssa G. Ashbaugh, a third-year medical student at the University of California, Irvine.

The study also found that psoriasis had a greater adverse impact on well-being, as measured with the Dermatology Life Quality Index (DLQI). At entry into the trials from which these patients were drawn, the higher DLQI score, significantly lower quality of life, was nearly two times higher (13.78 vs. 7.31; P = .01) among the Latino patients, compared with White patients.

This is not the first study to show a greater negative impact from psoriasis on Latinos than Whites, according to Ms. Ashbaugh. For example, Latinos had the worse quality of life at baseline by DLQI score than White, Asians, or Black participants in a trial of etanercept that enrolled more than 2000 patients.

In this retrospective chart review, patient characteristics were evaluated in all 21 Latino patients enrolled in psoriasis clinical trials at the University of California, Irvine, in a recent period. They were matched by age and gender to an equal number of White patients participating in the same trials.

The mean age at diagnosis of psoriasis was older in the Latino group than in the White population (42.4 vs. 35.6 years; P = .20), but the difference did not reach statistical significance. The proportion of patients with severe disease on investigator global assessment was also greater but not significantly different in the Latino group, compared with the White group, respectively (42.9% vs. 28.6%; P = .10).

However, differences in the patterns of disease did reach significance. This included a lower mean Psoriasis Assessment Severity Index score of the trunk, axilla, and groin in Latinos (4.74 vs. 9.73; P = .02). But compared with White participants, Latinos had a higher mean percentage of body surface area involvement in the upper limbs (4.78 vs. 1.85; P = .004) and a higher percentage of total body surface area involvement (20.50 vs. 10.03; P = .02).

“While White patients were found to have lived many more years with psoriasis, it is important for future studies to examine whether this is due to earlier onset or delayed diagnosis, given the fact that minorities are less likely to have access to a dermatologist,” reported Ms. Ashbaugh, who performed this work under the guidance of the senior author, Natasha Mesinkovska, MD, PhD, with the department of dermatology, University of California, Irvine.

Overall, the study suggested that body surface coverage and severity is not similarly distributed in Latinos relative to Whites. Although Ms. Ashbaugh conceded that the small sample size and retrospective design of this study are important limitations, she believes that her study, along with previously published studies that suggest psoriasis characteristics may differ meaningfully by race or ethnicity, raises issues that should be explored in future studies designed to confirm differences and whether those differences should affect management.

Other studies have suggested “there are notable differences in the presentation of psoriasis between racial and ethnic groups with the Latino population often presenting to physicians with more severe psoriasis and increased body surface area involvement,” Ms. Ashbaugh noted. Although this appears to be one of the first studies to examine psoriasis characteristics in Latinos relative to Whites, she believes this is an area ripe for further analysis.

Psoriasis “is not a rare occurrence” in non-White populations even if U.S. data suggest that the prevalence in “people of color is lower than that of psoriasis in the U.S. white population,” Amy McMichael, MD, chair of the department of dermatology, Wake Forest Baptist Medical Center, Winston-Salem, N.C., commented in an interview after the meeting. She agreed that it cannot be assumed that psoriasis in skin of color has the same manifestations or responds to treatment in the same way as in White patients.

“Studies have suggested that lesion thickness and, often, extent of disease can be worse in patients of color. Few studies to date have examined the efficacy of treatments and impact of disease in these populations,” she said.

One exception was a study Dr. McMichael and colleagues published last year on the efficacy and safety of the interleukin-17 receptor A antagonist brodalumab for psoriasis in patients of color. The study showed that Black, Latino, and Asian patients participating in the AMAGINE-2 and AMAGINE-3 trials achieved similar outcomes as White participants.

“We published this study because this is one of the first, if not the first, to have enough patients of color to actually draw conclusions about the efficacy of the biologic as well as the patient-reported outcomes,” she explained.

Like the author of the evaluation of Latino patients undertaken at the University of California, Irvine, Dr. McMichael said studies of psoriasis specific to patients of color are needed.

“We cannot assume all patients of color will have the same outcomes as their Caucasian counterparts. It is imperative to include those of color in future psoriasis treatment trials in order to determine the efficacy of new medications,” she added, specifically calling for collection of data on patient-reported outcomes.

Ms. Ashbaugh has no relevant financial relationships to disclose. Dr. McMichael’s disclosures included serving as an investigator and/or consultant for companies that included Allergan, Procter & Gamble, Johnson & Johnson, and Aclaris.

Latino patients participating in clinical trials of psoriasis treatments were found to have different patterns of disease and a lower level of quality of life, compared with White participants in the same studies, according to new data presented at the virtual Skin of Color Update 2020.

“Our findings demonstrate that, though White psoriasis patients may have higher severity in certain body regions such as the trunk, axilla, and groin areas, Latino psoriasis patients have a greater distribution of involvement, particularly in their upper limbs,” reported Alyssa G. Ashbaugh, a third-year medical student at the University of California, Irvine.

The study also found that psoriasis had a greater adverse impact on well-being, as measured with the Dermatology Life Quality Index (DLQI). At entry into the trials from which these patients were drawn, the higher DLQI score, significantly lower quality of life, was nearly two times higher (13.78 vs. 7.31; P = .01) among the Latino patients, compared with White patients.

This is not the first study to show a greater negative impact from psoriasis on Latinos than Whites, according to Ms. Ashbaugh. For example, Latinos had the worse quality of life at baseline by DLQI score than White, Asians, or Black participants in a trial of etanercept that enrolled more than 2000 patients.

In this retrospective chart review, patient characteristics were evaluated in all 21 Latino patients enrolled in psoriasis clinical trials at the University of California, Irvine, in a recent period. They were matched by age and gender to an equal number of White patients participating in the same trials.

The mean age at diagnosis of psoriasis was older in the Latino group than in the White population (42.4 vs. 35.6 years; P = .20), but the difference did not reach statistical significance. The proportion of patients with severe disease on investigator global assessment was also greater but not significantly different in the Latino group, compared with the White group, respectively (42.9% vs. 28.6%; P = .10).

However, differences in the patterns of disease did reach significance. This included a lower mean Psoriasis Assessment Severity Index score of the trunk, axilla, and groin in Latinos (4.74 vs. 9.73; P = .02). But compared with White participants, Latinos had a higher mean percentage of body surface area involvement in the upper limbs (4.78 vs. 1.85; P = .004) and a higher percentage of total body surface area involvement (20.50 vs. 10.03; P = .02).

“While White patients were found to have lived many more years with psoriasis, it is important for future studies to examine whether this is due to earlier onset or delayed diagnosis, given the fact that minorities are less likely to have access to a dermatologist,” reported Ms. Ashbaugh, who performed this work under the guidance of the senior author, Natasha Mesinkovska, MD, PhD, with the department of dermatology, University of California, Irvine.

Overall, the study suggested that body surface coverage and severity is not similarly distributed in Latinos relative to Whites. Although Ms. Ashbaugh conceded that the small sample size and retrospective design of this study are important limitations, she believes that her study, along with previously published studies that suggest psoriasis characteristics may differ meaningfully by race or ethnicity, raises issues that should be explored in future studies designed to confirm differences and whether those differences should affect management.

Other studies have suggested “there are notable differences in the presentation of psoriasis between racial and ethnic groups with the Latino population often presenting to physicians with more severe psoriasis and increased body surface area involvement,” Ms. Ashbaugh noted. Although this appears to be one of the first studies to examine psoriasis characteristics in Latinos relative to Whites, she believes this is an area ripe for further analysis.

Psoriasis “is not a rare occurrence” in non-White populations even if U.S. data suggest that the prevalence in “people of color is lower than that of psoriasis in the U.S. white population,” Amy McMichael, MD, chair of the department of dermatology, Wake Forest Baptist Medical Center, Winston-Salem, N.C., commented in an interview after the meeting. She agreed that it cannot be assumed that psoriasis in skin of color has the same manifestations or responds to treatment in the same way as in White patients.

“Studies have suggested that lesion thickness and, often, extent of disease can be worse in patients of color. Few studies to date have examined the efficacy of treatments and impact of disease in these populations,” she said.

One exception was a study Dr. McMichael and colleagues published last year on the efficacy and safety of the interleukin-17 receptor A antagonist brodalumab for psoriasis in patients of color. The study showed that Black, Latino, and Asian patients participating in the AMAGINE-2 and AMAGINE-3 trials achieved similar outcomes as White participants.

“We published this study because this is one of the first, if not the first, to have enough patients of color to actually draw conclusions about the efficacy of the biologic as well as the patient-reported outcomes,” she explained.

Like the author of the evaluation of Latino patients undertaken at the University of California, Irvine, Dr. McMichael said studies of psoriasis specific to patients of color are needed.

“We cannot assume all patients of color will have the same outcomes as their Caucasian counterparts. It is imperative to include those of color in future psoriasis treatment trials in order to determine the efficacy of new medications,” she added, specifically calling for collection of data on patient-reported outcomes.

Ms. Ashbaugh has no relevant financial relationships to disclose. Dr. McMichael’s disclosures included serving as an investigator and/or consultant for companies that included Allergan, Procter & Gamble, Johnson & Johnson, and Aclaris.

May 20 of this plague year, Reuters reported the death of a 32-year-old Florida nurse who had worked tirelessly to treat patients with COVID-19.¹ The presumption is that, like so many selfless health care providers (HCPs), this nurse was exposed to and then sadly succumbed to the virus. That presumption would be wrong: COVID-19 did not take his young life. The other pandemic—addiction— did. Bereaved friends and family reported that the nurse had been in recovery from opioid use disorder (OUD) before the onslaught of the public health crisis. The chronicle of his relapse is instructive for the devastating effect COVID-19 has had on persons struggling with addiction, even those like the nurse who was in sustained remission from OUD with a bright future.

Many of the themes are familiar to HCPs and have been the subject of prior columns in this COVID-19 series. The nurse experienced acute stress symptoms, such as nightmares from the repeated crises of sick and dying patients in the intensive care unit where he worked.² Like so many other HCPs, while he was desperately trying to save others, he also worried about having sufficient access to appropriate personal protective equipment (PPE).

Most relevant to this column, the caregiver was unable to access his primary source of support for his sobriety—attendance at 12-step meetings. Social distancing, which is one of the only proven means we have of reducing transmission of the virus, has had unintended consequences. Although many have found virtual connections rewarding, this nurse needed the curtailed face-to-face contact. The courage that had led him to volunteer for hazardous duty unwontedly resulted in his estrangement: Friends feared that he would expose them to the virus, and he worried that he would expose his family to danger. As in the 1918 flu pandemic, the humans we depend on for reality testing and companionship have been cruelly transformed into potential vectors of the virus.³

Isolation is the worst of all possible counselors as the great Spanish philosopher of alienation Miguel de Unamuno has argued. The deceptive promise of a rapid deliverance from anxiety and pain that substances of abuse proffer apparently led the nurse back to opioids. The virtue of being clean permitted the dirty drug to take advantage of the nurses’ reduced physiologic tolerance to opioids. It is suspected but not confirmed that he fatally overdosed alone in his car.

This Florida nurse is an especially tragic example of a terrible phenomenon being repeated all over the country. And the epidemic of substance use disorders (SUDs) related to COVID-19 is not confined to the US; there are similar reports from other afflicted nations, making addiction truly the other pandemic.⁴ The Centers for Disease Control and Prevention reported that 13.3% of American adults have started or increased their substance use as a means of managing the negative emotions associated with the pandemic.⁵ Also from March to May 2020, researchers in Baltimore found a 17.6% increase in suspected overdoses in counties advising social distancing and/or mandating stay at home orders.⁵

These data reinforce a well-known maxim in the addiction community that “addiction is a disease of isolation.”^6-8 The burden of the lockdown falls harder on many of the patients we treat in the federal health care system whose other mental and physical health conditions, including chronic pain, depression, and posttraumatic stress disorder already placed them at elevated risk of SUDs.⁹ Director of the National Institute of Drug Abuse Nora Volkow, MD, recently traced the well-known arc from isolation to increased use of drugs and alcohol.¹⁰ Isolation is stressful and amplifies negative thoughts, dysphoria, and fearful emotions, which are recognized triggers for the use of substances of abuse. The usually available means of coping with craving, and in many cases withdrawal, such as prescribed medications, visits to therapists, participation in support groups are either not available or much more difficult to access.¹⁰ Nor are those without a current or even historical SUD immune to the psychosocial pressures of the pandemic: Isolation also constitutes a risk for the development of de novo addiction particularly among already marginalized groups, such as the elderly and disabled.

The federal government has initiated several important measures to reduce the adverse impact of isolation on persons with SUDs. The Drug Enforcement Administration is exempting qualified practitioners of medication-assisted treatment from the in-person evaluation that is usually required for the prescription of controlled substances, including buprenorphine. This exemption applies to both established patient prescriptions for buprenorphine and new buprenorphine patient prescriptions.¹¹ These and other administrative contingencies at the federal government level can assist persons with OUD to continue to receive medicationassisted treatment.

As individual clinicians in federal practice, we alone cannot engineer such major policy accommodations in response to COVID-19, yet we can still make a difference in the lives of our patients. We can focus a few minutes of our telehealth interactions on checking in with patients who have a history or a current SUD. We can remember to use evidence-based screens for these patients and those with other risk factors to detect drug or alcohol use before it becomes a disorder. And we can identify and refer not only patients but also our beleaguered colleagues who feel alone at sea—to the many lifelines our agencies have cast into what other commentators have referred to as a Perfect Storm of COVID-19 and the opioid crisis (Table).¹²

May 20 of this plague year, Reuters reported the death of a 32-year-old Florida nurse who had worked tirelessly to treat patients with COVID-19.¹ The presumption is that, like so many selfless health care providers (HCPs), this nurse was exposed to and then sadly succumbed to the virus. That presumption would be wrong: COVID-19 did not take his young life. The other pandemic—addiction— did. Bereaved friends and family reported that the nurse had been in recovery from opioid use disorder (OUD) before the onslaught of the public health crisis. The chronicle of his relapse is instructive for the devastating effect COVID-19 has had on persons struggling with addiction, even those like the nurse who was in sustained remission from OUD with a bright future.

Many of the themes are familiar to HCPs and have been the subject of prior columns in this COVID-19 series. The nurse experienced acute stress symptoms, such as nightmares from the repeated crises of sick and dying patients in the intensive care unit where he worked.² Like so many other HCPs, while he was desperately trying to save others, he also worried about having sufficient access to appropriate personal protective equipment (PPE).

Most relevant to this column, the caregiver was unable to access his primary source of support for his sobriety—attendance at 12-step meetings. Social distancing, which is one of the only proven means we have of reducing transmission of the virus, has had unintended consequences. Although many have found virtual connections rewarding, this nurse needed the curtailed face-to-face contact. The courage that had led him to volunteer for hazardous duty unwontedly resulted in his estrangement: Friends feared that he would expose them to the virus, and he worried that he would expose his family to danger. As in the 1918 flu pandemic, the humans we depend on for reality testing and companionship have been cruelly transformed into potential vectors of the virus.³

Isolation is the worst of all possible counselors as the great Spanish philosopher of alienation Miguel de Unamuno has argued. The deceptive promise of a rapid deliverance from anxiety and pain that substances of abuse proffer apparently led the nurse back to opioids. The virtue of being clean permitted the dirty drug to take advantage of the nurses’ reduced physiologic tolerance to opioids. It is suspected but not confirmed that he fatally overdosed alone in his car.

This Florida nurse is an especially tragic example of a terrible phenomenon being repeated all over the country. And the epidemic of substance use disorders (SUDs) related to COVID-19 is not confined to the US; there are similar reports from other afflicted nations, making addiction truly the other pandemic.⁴ The Centers for Disease Control and Prevention reported that 13.3% of American adults have started or increased their substance use as a means of managing the negative emotions associated with the pandemic.⁵ Also from March to May 2020, researchers in Baltimore found a 17.6% increase in suspected overdoses in counties advising social distancing and/or mandating stay at home orders.⁵

These data reinforce a well-known maxim in the addiction community that “addiction is a disease of isolation.”^6-8 The burden of the lockdown falls harder on many of the patients we treat in the federal health care system whose other mental and physical health conditions, including chronic pain, depression, and posttraumatic stress disorder already placed them at elevated risk of SUDs.⁹ Director of the National Institute of Drug Abuse Nora Volkow, MD, recently traced the well-known arc from isolation to increased use of drugs and alcohol.¹⁰ Isolation is stressful and amplifies negative thoughts, dysphoria, and fearful emotions, which are recognized triggers for the use of substances of abuse. The usually available means of coping with craving, and in many cases withdrawal, such as prescribed medications, visits to therapists, participation in support groups are either not available or much more difficult to access.¹⁰ Nor are those without a current or even historical SUD immune to the psychosocial pressures of the pandemic: Isolation also constitutes a risk for the development of de novo addiction particularly among already marginalized groups, such as the elderly and disabled.

The federal government has initiated several important measures to reduce the adverse impact of isolation on persons with SUDs. The Drug Enforcement Administration is exempting qualified practitioners of medication-assisted treatment from the in-person evaluation that is usually required for the prescription of controlled substances, including buprenorphine. This exemption applies to both established patient prescriptions for buprenorphine and new buprenorphine patient prescriptions.¹¹ These and other administrative contingencies at the federal government level can assist persons with OUD to continue to receive medicationassisted treatment.

As individual clinicians in federal practice, we alone cannot engineer such major policy accommodations in response to COVID-19, yet we can still make a difference in the lives of our patients. We can focus a few minutes of our telehealth interactions on checking in with patients who have a history or a current SUD. We can remember to use evidence-based screens for these patients and those with other risk factors to detect drug or alcohol use before it becomes a disorder. And we can identify and refer not only patients but also our beleaguered colleagues who feel alone at sea—to the many lifelines our agencies have cast into what other commentators have referred to as a Perfect Storm of COVID-19 and the opioid crisis (Table).¹²

May 20 of this plague year, Reuters reported the death of a 32-year-old Florida nurse who had worked tirelessly to treat patients with COVID-19.¹ The presumption is that, like so many selfless health care providers (HCPs), this nurse was exposed to and then sadly succumbed to the virus. That presumption would be wrong: COVID-19 did not take his young life. The other pandemic—addiction— did. Bereaved friends and family reported that the nurse had been in recovery from opioid use disorder (OUD) before the onslaught of the public health crisis. The chronicle of his relapse is instructive for the devastating effect COVID-19 has had on persons struggling with addiction, even those like the nurse who was in sustained remission from OUD with a bright future.

Many of the themes are familiar to HCPs and have been the subject of prior columns in this COVID-19 series. The nurse experienced acute stress symptoms, such as nightmares from the repeated crises of sick and dying patients in the intensive care unit where he worked.² Like so many other HCPs, while he was desperately trying to save others, he also worried about having sufficient access to appropriate personal protective equipment (PPE).

Most relevant to this column, the caregiver was unable to access his primary source of support for his sobriety—attendance at 12-step meetings. Social distancing, which is one of the only proven means we have of reducing transmission of the virus, has had unintended consequences. Although many have found virtual connections rewarding, this nurse needed the curtailed face-to-face contact. The courage that had led him to volunteer for hazardous duty unwontedly resulted in his estrangement: Friends feared that he would expose them to the virus, and he worried that he would expose his family to danger. As in the 1918 flu pandemic, the humans we depend on for reality testing and companionship have been cruelly transformed into potential vectors of the virus.³

Isolation is the worst of all possible counselors as the great Spanish philosopher of alienation Miguel de Unamuno has argued. The deceptive promise of a rapid deliverance from anxiety and pain that substances of abuse proffer apparently led the nurse back to opioids. The virtue of being clean permitted the dirty drug to take advantage of the nurses’ reduced physiologic tolerance to opioids. It is suspected but not confirmed that he fatally overdosed alone in his car.

This Florida nurse is an especially tragic example of a terrible phenomenon being repeated all over the country. And the epidemic of substance use disorders (SUDs) related to COVID-19 is not confined to the US; there are similar reports from other afflicted nations, making addiction truly the other pandemic.⁴ The Centers for Disease Control and Prevention reported that 13.3% of American adults have started or increased their substance use as a means of managing the negative emotions associated with the pandemic.⁵ Also from March to May 2020, researchers in Baltimore found a 17.6% increase in suspected overdoses in counties advising social distancing and/or mandating stay at home orders.⁵

These data reinforce a well-known maxim in the addiction community that “addiction is a disease of isolation.”^6-8 The burden of the lockdown falls harder on many of the patients we treat in the federal health care system whose other mental and physical health conditions, including chronic pain, depression, and posttraumatic stress disorder already placed them at elevated risk of SUDs.⁹ Director of the National Institute of Drug Abuse Nora Volkow, MD, recently traced the well-known arc from isolation to increased use of drugs and alcohol.¹⁰ Isolation is stressful and amplifies negative thoughts, dysphoria, and fearful emotions, which are recognized triggers for the use of substances of abuse. The usually available means of coping with craving, and in many cases withdrawal, such as prescribed medications, visits to therapists, participation in support groups are either not available or much more difficult to access.¹⁰ Nor are those without a current or even historical SUD immune to the psychosocial pressures of the pandemic: Isolation also constitutes a risk for the development of de novo addiction particularly among already marginalized groups, such as the elderly and disabled.

The federal government has initiated several important measures to reduce the adverse impact of isolation on persons with SUDs. The Drug Enforcement Administration is exempting qualified practitioners of medication-assisted treatment from the in-person evaluation that is usually required for the prescription of controlled substances, including buprenorphine. This exemption applies to both established patient prescriptions for buprenorphine and new buprenorphine patient prescriptions.¹¹ These and other administrative contingencies at the federal government level can assist persons with OUD to continue to receive medicationassisted treatment.

As individual clinicians in federal practice, we alone cannot engineer such major policy accommodations in response to COVID-19, yet we can still make a difference in the lives of our patients. We can focus a few minutes of our telehealth interactions on checking in with patients who have a history or a current SUD. We can remember to use evidence-based screens for these patients and those with other risk factors to detect drug or alcohol use before it becomes a disorder. And we can identify and refer not only patients but also our beleaguered colleagues who feel alone at sea—to the many lifelines our agencies have cast into what other commentators have referred to as a Perfect Storm of COVID-19 and the opioid crisis (Table).¹²

In a new review, a group of infectious disease experts have summarized and made recommendations about recent findings regarding infections that can occur during treatment with an evolving set of targeted and biologic therapies for rheumatoid arthritis and psoriatic arthritis.

“We claim for the need for multicenter registries and multidisciplinary approaches, for new vaccines trials in RA and PsA, and for better defining when and how biologics can be restarted after severe infections,” lead author Olivier Lortholary, MD, of the Institut Pasteur in Paris, and his coauthors wrote in Annals of the Rheumatic Diseases.

Assessing infection risk related to various inhibitors

Regarding infections caused by TNF-alpha inhibitors (TNFIs), the experts acknowledged a broad increase in risk for mycobacterial and fungal infections, especially tuberculosis and histoplasmosis. They added that patients on TNFIs are more prone to developing pneumonia and soft tissue infections, while smaller studies have indicated a higher risk of listeriosis, legionellosis, herpes zoster (HZ), and reactivation of chronic hepatitis B virus infection.

As for recommendations, they endorsed discontinuing TNFIs when a serious infection occurs and not restarting until after treatment and clinical response. Patients should be screened for latent tuberculosis infection (LTBI) before starting the drug, and anti-TB drugs should be presented to patients with LTBI so they do not progress to active TB.

Regarding other biologics, they cited several studies indicating that IL-6 inhibitors can increase infection risks in RA patients at a rate similar to TNFIs. Among the most common infections were pneumonia and cellulitis. In addition, although PsA patients on IL-17 inhibitors have a dose-dependent risk of mild to moderate mucocutaneous candidiasis, there was no increased risk of serious opportunistic infections like TB.

In assessing JAK inhibitors, they cited a pooled analysis that indicated pneumonia and skin and soft-tissue infections as the most common and noted the high incidence of HZ, compared with other infections. They added that abatacept (Orencia) did not appear to increase risk of infections in RA patients, such as HZ, dermatomycosis, candidiasis, or endemic mycoses. Those same patients did not see an increased overall infection risk after treatment with rituximab (Rituxan), and clinical trials containing treatment with apremilast (Otezla) reported a rare occurrence of serious infections.

Recommendation-wise, they endorsed screening for LTBI before starting IL-6 inhibitors and antiviral prophylaxis with acyclovir in particularly at-risk patients on JAK inhibitors. Age-appropriate influenza vaccinations were also recommended for rituximab, because of the development of rituximab-induced hypogammaglobulinemia.
 

Prediction and prevention

When it comes to predicting infections in patients on biologics, the experts wrote that it “remains a challenge.” The potential effects of pretreatment underlying disease, the lack of validated biomarkers, and the relatively low rate of infections all combine to stymie prediction. That said, they acknowledged ongoing efforts in monitoring lymphocyte subpopulation counts and immunoglobin levels, as well as a clinical score called the RABBIT Risk Score for Infections, which was validated in two separate cohorts.

“As Yogi Berra said, predictions are hard, especially about the future,” Dr. Kavanaugh said. “Discussions with your patient are always important.”

In regard to overall prevention, they acknowledged that most of their recommendations are of low evidence, except for antiviral prophylaxis for hepatitis B patients on rituximab and the aforementioned LTBI therapy in patients on TNFIs. Broadly, they advocated for all RA and PsA patients to receive a full infectious disease evaluation before the start of targeted and biologic therapies.

They also addressed vaccinations, recommending an evaluation of the patient’s immunization history and potentially planning a catch-up schedule for those in need of the influenza vaccine, a diphtheria-tetanus-pertussis booster, or the pneumococcal vaccine. More broadly, they stated that “a better response is expected if [non-live] vaccination is performed before the introduction of immunosuppressive drugs.” They added that live vaccines should be administered as soon as possible.
 

What rheumatologists can do

“So how do you mitigate risk?” Dr. Winthrop asked. “You have to be able to predict the risk, see what’s modifiable, and try to act on it. A lot of the risk of infection has more to do with the patient than the therapy.

“You try to minimize what you’re doing to the patient, particularly around steroids,” he said. “And then you think about screening and vaccinations. Rheumatologists need to be involved in those conversations because they’re the ones who know how these drugs interact with vaccines. A lot of the drugs might dumb down vaccine responses. Be sure to consider that and give the vaccines at times that will optimize their immunogenicity and likely efficacy.”

“Thankfully, infections are not that common,” Dr. Kavanaugh said. “Rheumatologists depend on data from trials, but more safety data comes from registry data and personal and shared experience.”

The authors declared no potential conflicts of interest.

SOURCE: Lortholary O et al. Ann Rheum Dis. 2020 Sep 22. doi: 10.1136/annrheumdis-2020-217092.

In a new review, a group of infectious disease experts have summarized and made recommendations about recent findings regarding infections that can occur during treatment with an evolving set of targeted and biologic therapies for rheumatoid arthritis and psoriatic arthritis.

“We claim for the need for multicenter registries and multidisciplinary approaches, for new vaccines trials in RA and PsA, and for better defining when and how biologics can be restarted after severe infections,” lead author Olivier Lortholary, MD, of the Institut Pasteur in Paris, and his coauthors wrote in Annals of the Rheumatic Diseases.

Assessing infection risk related to various inhibitors

Regarding infections caused by TNF-alpha inhibitors (TNFIs), the experts acknowledged a broad increase in risk for mycobacterial and fungal infections, especially tuberculosis and histoplasmosis. They added that patients on TNFIs are more prone to developing pneumonia and soft tissue infections, while smaller studies have indicated a higher risk of listeriosis, legionellosis, herpes zoster (HZ), and reactivation of chronic hepatitis B virus infection.

As for recommendations, they endorsed discontinuing TNFIs when a serious infection occurs and not restarting until after treatment and clinical response. Patients should be screened for latent tuberculosis infection (LTBI) before starting the drug, and anti-TB drugs should be presented to patients with LTBI so they do not progress to active TB.

Regarding other biologics, they cited several studies indicating that IL-6 inhibitors can increase infection risks in RA patients at a rate similar to TNFIs. Among the most common infections were pneumonia and cellulitis. In addition, although PsA patients on IL-17 inhibitors have a dose-dependent risk of mild to moderate mucocutaneous candidiasis, there was no increased risk of serious opportunistic infections like TB.

In assessing JAK inhibitors, they cited a pooled analysis that indicated pneumonia and skin and soft-tissue infections as the most common and noted the high incidence of HZ, compared with other infections. They added that abatacept (Orencia) did not appear to increase risk of infections in RA patients, such as HZ, dermatomycosis, candidiasis, or endemic mycoses. Those same patients did not see an increased overall infection risk after treatment with rituximab (Rituxan), and clinical trials containing treatment with apremilast (Otezla) reported a rare occurrence of serious infections.

Recommendation-wise, they endorsed screening for LTBI before starting IL-6 inhibitors and antiviral prophylaxis with acyclovir in particularly at-risk patients on JAK inhibitors. Age-appropriate influenza vaccinations were also recommended for rituximab, because of the development of rituximab-induced hypogammaglobulinemia.
 

Prediction and prevention

When it comes to predicting infections in patients on biologics, the experts wrote that it “remains a challenge.” The potential effects of pretreatment underlying disease, the lack of validated biomarkers, and the relatively low rate of infections all combine to stymie prediction. That said, they acknowledged ongoing efforts in monitoring lymphocyte subpopulation counts and immunoglobin levels, as well as a clinical score called the RABBIT Risk Score for Infections, which was validated in two separate cohorts.

“As Yogi Berra said, predictions are hard, especially about the future,” Dr. Kavanaugh said. “Discussions with your patient are always important.”

In regard to overall prevention, they acknowledged that most of their recommendations are of low evidence, except for antiviral prophylaxis for hepatitis B patients on rituximab and the aforementioned LTBI therapy in patients on TNFIs. Broadly, they advocated for all RA and PsA patients to receive a full infectious disease evaluation before the start of targeted and biologic therapies.

They also addressed vaccinations, recommending an evaluation of the patient’s immunization history and potentially planning a catch-up schedule for those in need of the influenza vaccine, a diphtheria-tetanus-pertussis booster, or the pneumococcal vaccine. More broadly, they stated that “a better response is expected if [non-live] vaccination is performed before the introduction of immunosuppressive drugs.” They added that live vaccines should be administered as soon as possible.
 

What rheumatologists can do

“So how do you mitigate risk?” Dr. Winthrop asked. “You have to be able to predict the risk, see what’s modifiable, and try to act on it. A lot of the risk of infection has more to do with the patient than the therapy.

“You try to minimize what you’re doing to the patient, particularly around steroids,” he said. “And then you think about screening and vaccinations. Rheumatologists need to be involved in those conversations because they’re the ones who know how these drugs interact with vaccines. A lot of the drugs might dumb down vaccine responses. Be sure to consider that and give the vaccines at times that will optimize their immunogenicity and likely efficacy.”

“Thankfully, infections are not that common,” Dr. Kavanaugh said. “Rheumatologists depend on data from trials, but more safety data comes from registry data and personal and shared experience.”

The authors declared no potential conflicts of interest.

SOURCE: Lortholary O et al. Ann Rheum Dis. 2020 Sep 22. doi: 10.1136/annrheumdis-2020-217092.

In a new review, a group of infectious disease experts have summarized and made recommendations about recent findings regarding infections that can occur during treatment with an evolving set of targeted and biologic therapies for rheumatoid arthritis and psoriatic arthritis.

“We claim for the need for multicenter registries and multidisciplinary approaches, for new vaccines trials in RA and PsA, and for better defining when and how biologics can be restarted after severe infections,” lead author Olivier Lortholary, MD, of the Institut Pasteur in Paris, and his coauthors wrote in Annals of the Rheumatic Diseases.

Assessing infection risk related to various inhibitors

Regarding infections caused by TNF-alpha inhibitors (TNFIs), the experts acknowledged a broad increase in risk for mycobacterial and fungal infections, especially tuberculosis and histoplasmosis. They added that patients on TNFIs are more prone to developing pneumonia and soft tissue infections, while smaller studies have indicated a higher risk of listeriosis, legionellosis, herpes zoster (HZ), and reactivation of chronic hepatitis B virus infection.

As for recommendations, they endorsed discontinuing TNFIs when a serious infection occurs and not restarting until after treatment and clinical response. Patients should be screened for latent tuberculosis infection (LTBI) before starting the drug, and anti-TB drugs should be presented to patients with LTBI so they do not progress to active TB.

Regarding other biologics, they cited several studies indicating that IL-6 inhibitors can increase infection risks in RA patients at a rate similar to TNFIs. Among the most common infections were pneumonia and cellulitis. In addition, although PsA patients on IL-17 inhibitors have a dose-dependent risk of mild to moderate mucocutaneous candidiasis, there was no increased risk of serious opportunistic infections like TB.

In assessing JAK inhibitors, they cited a pooled analysis that indicated pneumonia and skin and soft-tissue infections as the most common and noted the high incidence of HZ, compared with other infections. They added that abatacept (Orencia) did not appear to increase risk of infections in RA patients, such as HZ, dermatomycosis, candidiasis, or endemic mycoses. Those same patients did not see an increased overall infection risk after treatment with rituximab (Rituxan), and clinical trials containing treatment with apremilast (Otezla) reported a rare occurrence of serious infections.

Recommendation-wise, they endorsed screening for LTBI before starting IL-6 inhibitors and antiviral prophylaxis with acyclovir in particularly at-risk patients on JAK inhibitors. Age-appropriate influenza vaccinations were also recommended for rituximab, because of the development of rituximab-induced hypogammaglobulinemia.
 

Prediction and prevention

When it comes to predicting infections in patients on biologics, the experts wrote that it “remains a challenge.” The potential effects of pretreatment underlying disease, the lack of validated biomarkers, and the relatively low rate of infections all combine to stymie prediction. That said, they acknowledged ongoing efforts in monitoring lymphocyte subpopulation counts and immunoglobin levels, as well as a clinical score called the RABBIT Risk Score for Infections, which was validated in two separate cohorts.

“As Yogi Berra said, predictions are hard, especially about the future,” Dr. Kavanaugh said. “Discussions with your patient are always important.”

In regard to overall prevention, they acknowledged that most of their recommendations are of low evidence, except for antiviral prophylaxis for hepatitis B patients on rituximab and the aforementioned LTBI therapy in patients on TNFIs. Broadly, they advocated for all RA and PsA patients to receive a full infectious disease evaluation before the start of targeted and biologic therapies.

They also addressed vaccinations, recommending an evaluation of the patient’s immunization history and potentially planning a catch-up schedule for those in need of the influenza vaccine, a diphtheria-tetanus-pertussis booster, or the pneumococcal vaccine. More broadly, they stated that “a better response is expected if [non-live] vaccination is performed before the introduction of immunosuppressive drugs.” They added that live vaccines should be administered as soon as possible.
 

What rheumatologists can do

“So how do you mitigate risk?” Dr. Winthrop asked. “You have to be able to predict the risk, see what’s modifiable, and try to act on it. A lot of the risk of infection has more to do with the patient than the therapy.

“You try to minimize what you’re doing to the patient, particularly around steroids,” he said. “And then you think about screening and vaccinations. Rheumatologists need to be involved in those conversations because they’re the ones who know how these drugs interact with vaccines. A lot of the drugs might dumb down vaccine responses. Be sure to consider that and give the vaccines at times that will optimize their immunogenicity and likely efficacy.”

“Thankfully, infections are not that common,” Dr. Kavanaugh said. “Rheumatologists depend on data from trials, but more safety data comes from registry data and personal and shared experience.”

The authors declared no potential conflicts of interest.

SOURCE: Lortholary O et al. Ann Rheum Dis. 2020 Sep 22. doi: 10.1136/annrheumdis-2020-217092.

The risk of severe outcomes from COVID-19 infection in patients with multiple sclerosis (MS) seems to align with that seen in the general population, new U.S. data suggest. A separate study from the United Kingdom also found similar trends of rates of COVID-19 infection in patients with MS and the general population.

Both studies were presented Sept. 26 at a special session on multiple sclerosis and COVID-19 at a final “Encore” event as part of the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2020, this year known as MSVirtual2020.

The U.S. data appear consistent with studies from several other countries, in that worse COVID-19 outcomes increase with age and higher disability levels, both of which would be expected from findings in the general population.

The U.S. data also show a clear effect of race in MS, with higher rates of adverse COVID-19 outcomes in Black patients, again in line with what is seen in the general population.

“I would say the results from our study and in general do not suggest that MS itself is associated with higher risks of severe COVID-19 outcomes, compared with the general population,” said Amber Salter, PhD.

Dr. Salter, who is assistant professor of biostatistics at Washington University, St. Louis, presented data from the COViMS North American registry, set up for health care providers to report persons with MS who are infected with COVID-19.

The COViMS registry so far has information on 858 patients with MS who have COVID-19 (80% verified by a positive test), as reported from 150 different health care providers in the United States and Canada. The average age was 48 years, with average disease duration of 13.6 years. MS clinical course was reported as relapsing remitting in 78%, secondary progressive in 15%, and primary progressive in 5%. Most patients (72%) were fully ambulatory, 16% could walk with assistance, and 12% were nonambulatory.

Severe COVID-19 outcomes were classified as mortality (which occurred in 5.7% of the cohort), mortality/ICU admission (13.6%) and mortality/ICU admission/hospitalization (30.2%).

Results were adjusted for many different covariates, including sex, age, smoking, MS clinical course (relapsing, progressive), disease duration, ambulation, individual comorbidities (cardiovascular disease, cerebrovascular disease, chronic kidney disease, chronic lung disease, diabetes, hypertension, morbid obesity), and disease-modifying therapy use.

In multivariable logistic regression analyses, older age, having chronic renal disease, and being nonambulatory were consistently associated with increased odds of poorer outcomes. Chronic kidney disease had the strongest association with mortality (odds ratio, 28.6; P < .001). Other factors associated with mortality included cardiovascular disease (OR, 4.35; P = .009); age (OR per 10 years, 1.91; P = .012), and male sex (OR, 2.60; P = .041).

Patients who were nonambulatory had a higher risk of mortality/ICU admission/hospitalization (OR, 3.32; P = .003). This endpoint was also increased in patients on anti-CD20 drugs, compared with other disease-modifying treatment (OR, 2.31; P = .002), consistent with results from at least two other studies.

Disease-modifying therapy in general was not associated with an increased risk of worse outcomes. “There was some concern at the outset about the effect of disease-modifying therapies on COVID-19 outcomes, but most studies have not found an increased risk of worse outcomes in patients on such drug treatments, with the possible exception of anti-CD20 drugs,” Dr. Salter said.

“Some disease-modifying therapies may actually be protective (particularly interferon) and studies are investigating whether they may have a role in the treatment of COVID-19,” she added.

“The factors in MS patients that we and others have found to be associated with worse COVID-19 outcomes may not be specific to MS. Older age is known to be a primary risk factor for worse COVID-19 outcomes in the general population, and increasing disability presumably tracks with worse general heath,” Dr. Salter commented.

“I would say the overall data are fairly reassuring for MS patents,” she concluded.
 

Black patients have higher risk

One worrying finding in the North American data, however, was the effect of race. “We found an independent effect of race for worse COVID-19 outcomes in MS patients,” Dr. Slater said.

Of the 858 patients in the COViMS registry, 65.7% were White and 26.1% were Black. Black individuals were more likely to be younger, never smokers, have shorter MS duration, a relapsing MS course, and have comorbidities, compared with White patients. A higher proportion of Black patients had hypertension (40.2% vs 19.5%) and morbid obesity (17% vs. 9.5%).

Results showed that mortality rates were not statistically different between White and Black patients, but Black race was associated with increased risk of mortality and/or ICU admission, compared with White patients (16.9% vs. 12.8%), and multivariate logistic regression analysis showed Black race was independently associated with mortality/ICU admission after adjustments for covariates (OR, 3.7; P = .002).

Black race was also associated with increased risk of mortality/ICU admission/hospital admission (35.8% vs. 30.2%), and after adjustment for covariates this was found to be an independent predictor (OR, 1.7; P = .04).

“This higher COVID-19 risk in Black individuals is also seen in the general population, so these results are not that surprising and it doesn’t appear to be an effect specific to MS patients,” Dr. Salter commented.
 

U.K. data on risk of contracting COVID-19 

A U.K. study also suggested race to be an independent predictor in the risk of contracting COVID-19 in patients with MS.

The study of more than 5,000 patients with MS showed that those from a Black, Asian, and Minority Ethnic group were twice as likely to report having COVID-19 than those who were White.

The study, which was conducted during the U.K. lockdown, also found that the trend of COVID-19 infection in patients with MS is comparable with that of the U.K. general population.

Presenting the data, Afagh Garjani, MD, concluded: “During a period with strict physical distancing measures, patients with MS are not at an increased risk of contracting COVID-19.”

Dr. Garjani, a neurology clinical research fellow at the University of Nottingham, (England), explained that the COVID-19 pandemic has introduced uncertainties into the MS community, and the focus so far has been the severity of infection among people with MS who have COVID-19.

“This approach has left questions about the risk of contracting disease in people with MS unanswered, which has implications as society gradually returns to normal,” she said.

Dr. Garjani presented data from the United Kingdom MS Register (UKMSR), which has been collecting demographic and MS-related data since 2011 from patients with MS throughout the United Kingdom.

On March 17 – just before the lockdown in United Kingdom – existing participants of the UKMSR were asked to join the COVID-19 study. The study was also advertised through social media. In this ongoing study, people with MS answered a COVID-19–related survey at participation and a different follow-up survey every 2 weeks depending on whether they contracted COVID-19.

The COVID-19 study included 5,309 patients with MS. The mean age of the study population was 52.4 years, 76.1% were female, and 95.7% were White. Of the 5,309 patients, 535 (10%) reported a self-diagnosis of COVID-19. Because of limited availability of tests in the United Kingdom at the time, only 75 patents had a positive polymerase chain reaction result.

“To our knowledge, this is the largest community-based study of COVID-19 in patients with MS worldwide,” Dr. Garjani said. She presented results from the period March 23 to June 24, when the United Kingdom was in a period of lockdown with vulnerable groups encouraged to self-isolate completely.

In this MS cohort, 47% reported self-isolating at some point. Those at older age and higher Expanded Disability Status Scale (EDSS) score were more likely to have self-isolated.

The researchers did not find that patients with progressive MS or those on disease-modifying therapies in general isolated more, but patients on monoclonal antibody drugs and fingolimod were more likely to self-isolate versus those on other therapies. “This may be because there are concerns about infection with these drugs and patients on these therapies may be more concerned about contracting COVID-19,” Dr. Garjani suggested.

In terms of contracting COVID, the researchers found a reduced risk of COVID-19 (self-diagnosed) in patients with older age and higher EDSS. “This is not really surprising that these patients were more likely to self-isolate,” Dr. Garjani commented.

No association was seen between type of MS, disease duration, disease-modifying therapy in general, and risk of COVID-19. No individual drug treatment increased risk versus no therapy or versus self-injectables. But there was an increased risk of contracting the virus in patients whose race was Black, Asian, or Minority Ethnic (OR, 2.2), which is in line with findings from the general population.

“This study is unique – the denominator is all people with MS. We are looking primarily at the risk of contracting COVID-19. Other studies are focusing more on people with MS who have COVID and assessing risk of a severe COVID outcome. Our results are not contradicting the findings from those studies,” Dr. Garjani said.

The results were similar only when patients with a confirmed COVID-19 test were considered.

In terms of outcomes in those who reported COVID-19 infection, preliminary results have not shown any MS factors – such as EDSS, age, type of MS, drug therapy in general – to be associated with outcome.

“Since the COVID-19 outbreak started there has been concern among MS patients, especially among those on disease-modifying therapies, about whether they are at increased risk of infection and severe disease,” Dr. Garjani said.

“We found similar trends of rates of infection in MS patients and the general population, and no signal of increased risks in those with higher EDSS or progressive MS. The caveat is that this study was conducted in a period of lockdown, but we adjusted for self-isolating behavior in the multivariable regression analysis,” she noted.

Dr. Salter is a statistical editor for the American Heart Association journal Circulation: Cardiovascular Imaging. Dr. Garjani has disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

The risk of severe outcomes from COVID-19 infection in patients with multiple sclerosis (MS) seems to align with that seen in the general population, new U.S. data suggest. A separate study from the United Kingdom also found similar trends of rates of COVID-19 infection in patients with MS and the general population.

Both studies were presented Sept. 26 at a special session on multiple sclerosis and COVID-19 at a final “Encore” event as part of the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2020, this year known as MSVirtual2020.

The U.S. data appear consistent with studies from several other countries, in that worse COVID-19 outcomes increase with age and higher disability levels, both of which would be expected from findings in the general population.

The U.S. data also show a clear effect of race in MS, with higher rates of adverse COVID-19 outcomes in Black patients, again in line with what is seen in the general population.

“I would say the results from our study and in general do not suggest that MS itself is associated with higher risks of severe COVID-19 outcomes, compared with the general population,” said Amber Salter, PhD.

Dr. Salter, who is assistant professor of biostatistics at Washington University, St. Louis, presented data from the COViMS North American registry, set up for health care providers to report persons with MS who are infected with COVID-19.

The COViMS registry so far has information on 858 patients with MS who have COVID-19 (80% verified by a positive test), as reported from 150 different health care providers in the United States and Canada. The average age was 48 years, with average disease duration of 13.6 years. MS clinical course was reported as relapsing remitting in 78%, secondary progressive in 15%, and primary progressive in 5%. Most patients (72%) were fully ambulatory, 16% could walk with assistance, and 12% were nonambulatory.

Severe COVID-19 outcomes were classified as mortality (which occurred in 5.7% of the cohort), mortality/ICU admission (13.6%) and mortality/ICU admission/hospitalization (30.2%).

Results were adjusted for many different covariates, including sex, age, smoking, MS clinical course (relapsing, progressive), disease duration, ambulation, individual comorbidities (cardiovascular disease, cerebrovascular disease, chronic kidney disease, chronic lung disease, diabetes, hypertension, morbid obesity), and disease-modifying therapy use.

In multivariable logistic regression analyses, older age, having chronic renal disease, and being nonambulatory were consistently associated with increased odds of poorer outcomes. Chronic kidney disease had the strongest association with mortality (odds ratio, 28.6; P < .001). Other factors associated with mortality included cardiovascular disease (OR, 4.35; P = .009); age (OR per 10 years, 1.91; P = .012), and male sex (OR, 2.60; P = .041).

Patients who were nonambulatory had a higher risk of mortality/ICU admission/hospitalization (OR, 3.32; P = .003). This endpoint was also increased in patients on anti-CD20 drugs, compared with other disease-modifying treatment (OR, 2.31; P = .002), consistent with results from at least two other studies.

Disease-modifying therapy in general was not associated with an increased risk of worse outcomes. “There was some concern at the outset about the effect of disease-modifying therapies on COVID-19 outcomes, but most studies have not found an increased risk of worse outcomes in patients on such drug treatments, with the possible exception of anti-CD20 drugs,” Dr. Salter said.

“Some disease-modifying therapies may actually be protective (particularly interferon) and studies are investigating whether they may have a role in the treatment of COVID-19,” she added.

“The factors in MS patients that we and others have found to be associated with worse COVID-19 outcomes may not be specific to MS. Older age is known to be a primary risk factor for worse COVID-19 outcomes in the general population, and increasing disability presumably tracks with worse general heath,” Dr. Salter commented.

“I would say the overall data are fairly reassuring for MS patents,” she concluded.
 

Black patients have higher risk

One worrying finding in the North American data, however, was the effect of race. “We found an independent effect of race for worse COVID-19 outcomes in MS patients,” Dr. Slater said.

Of the 858 patients in the COViMS registry, 65.7% were White and 26.1% were Black. Black individuals were more likely to be younger, never smokers, have shorter MS duration, a relapsing MS course, and have comorbidities, compared with White patients. A higher proportion of Black patients had hypertension (40.2% vs 19.5%) and morbid obesity (17% vs. 9.5%).

Results showed that mortality rates were not statistically different between White and Black patients, but Black race was associated with increased risk of mortality and/or ICU admission, compared with White patients (16.9% vs. 12.8%), and multivariate logistic regression analysis showed Black race was independently associated with mortality/ICU admission after adjustments for covariates (OR, 3.7; P = .002).

Black race was also associated with increased risk of mortality/ICU admission/hospital admission (35.8% vs. 30.2%), and after adjustment for covariates this was found to be an independent predictor (OR, 1.7; P = .04).

“This higher COVID-19 risk in Black individuals is also seen in the general population, so these results are not that surprising and it doesn’t appear to be an effect specific to MS patients,” Dr. Salter commented.
 

U.K. data on risk of contracting COVID-19 

A U.K. study also suggested race to be an independent predictor in the risk of contracting COVID-19 in patients with MS.

The study of more than 5,000 patients with MS showed that those from a Black, Asian, and Minority Ethnic group were twice as likely to report having COVID-19 than those who were White.

The study, which was conducted during the U.K. lockdown, also found that the trend of COVID-19 infection in patients with MS is comparable with that of the U.K. general population.

Presenting the data, Afagh Garjani, MD, concluded: “During a period with strict physical distancing measures, patients with MS are not at an increased risk of contracting COVID-19.”

Dr. Garjani, a neurology clinical research fellow at the University of Nottingham, (England), explained that the COVID-19 pandemic has introduced uncertainties into the MS community, and the focus so far has been the severity of infection among people with MS who have COVID-19.

“This approach has left questions about the risk of contracting disease in people with MS unanswered, which has implications as society gradually returns to normal,” she said.

Dr. Garjani presented data from the United Kingdom MS Register (UKMSR), which has been collecting demographic and MS-related data since 2011 from patients with MS throughout the United Kingdom.

On March 17 – just before the lockdown in United Kingdom – existing participants of the UKMSR were asked to join the COVID-19 study. The study was also advertised through social media. In this ongoing study, people with MS answered a COVID-19–related survey at participation and a different follow-up survey every 2 weeks depending on whether they contracted COVID-19.

The COVID-19 study included 5,309 patients with MS. The mean age of the study population was 52.4 years, 76.1% were female, and 95.7% were White. Of the 5,309 patients, 535 (10%) reported a self-diagnosis of COVID-19. Because of limited availability of tests in the United Kingdom at the time, only 75 patents had a positive polymerase chain reaction result.

“To our knowledge, this is the largest community-based study of COVID-19 in patients with MS worldwide,” Dr. Garjani said. She presented results from the period March 23 to June 24, when the United Kingdom was in a period of lockdown with vulnerable groups encouraged to self-isolate completely.

In this MS cohort, 47% reported self-isolating at some point. Those at older age and higher Expanded Disability Status Scale (EDSS) score were more likely to have self-isolated.

The researchers did not find that patients with progressive MS or those on disease-modifying therapies in general isolated more, but patients on monoclonal antibody drugs and fingolimod were more likely to self-isolate versus those on other therapies. “This may be because there are concerns about infection with these drugs and patients on these therapies may be more concerned about contracting COVID-19,” Dr. Garjani suggested.

In terms of contracting COVID, the researchers found a reduced risk of COVID-19 (self-diagnosed) in patients with older age and higher EDSS. “This is not really surprising that these patients were more likely to self-isolate,” Dr. Garjani commented.

No association was seen between type of MS, disease duration, disease-modifying therapy in general, and risk of COVID-19. No individual drug treatment increased risk versus no therapy or versus self-injectables. But there was an increased risk of contracting the virus in patients whose race was Black, Asian, or Minority Ethnic (OR, 2.2), which is in line with findings from the general population.

“This study is unique – the denominator is all people with MS. We are looking primarily at the risk of contracting COVID-19. Other studies are focusing more on people with MS who have COVID and assessing risk of a severe COVID outcome. Our results are not contradicting the findings from those studies,” Dr. Garjani said.

The results were similar only when patients with a confirmed COVID-19 test were considered.

In terms of outcomes in those who reported COVID-19 infection, preliminary results have not shown any MS factors – such as EDSS, age, type of MS, drug therapy in general – to be associated with outcome.

“Since the COVID-19 outbreak started there has been concern among MS patients, especially among those on disease-modifying therapies, about whether they are at increased risk of infection and severe disease,” Dr. Garjani said.

“We found similar trends of rates of infection in MS patients and the general population, and no signal of increased risks in those with higher EDSS or progressive MS. The caveat is that this study was conducted in a period of lockdown, but we adjusted for self-isolating behavior in the multivariable regression analysis,” she noted.

Dr. Salter is a statistical editor for the American Heart Association journal Circulation: Cardiovascular Imaging. Dr. Garjani has disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

The risk of severe outcomes from COVID-19 infection in patients with multiple sclerosis (MS) seems to align with that seen in the general population, new U.S. data suggest. A separate study from the United Kingdom also found similar trends of rates of COVID-19 infection in patients with MS and the general population.

Both studies were presented Sept. 26 at a special session on multiple sclerosis and COVID-19 at a final “Encore” event as part of the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2020, this year known as MSVirtual2020.

The U.S. data appear consistent with studies from several other countries, in that worse COVID-19 outcomes increase with age and higher disability levels, both of which would be expected from findings in the general population.

The U.S. data also show a clear effect of race in MS, with higher rates of adverse COVID-19 outcomes in Black patients, again in line with what is seen in the general population.

“I would say the results from our study and in general do not suggest that MS itself is associated with higher risks of severe COVID-19 outcomes, compared with the general population,” said Amber Salter, PhD.

Dr. Salter, who is assistant professor of biostatistics at Washington University, St. Louis, presented data from the COViMS North American registry, set up for health care providers to report persons with MS who are infected with COVID-19.

The COViMS registry so far has information on 858 patients with MS who have COVID-19 (80% verified by a positive test), as reported from 150 different health care providers in the United States and Canada. The average age was 48 years, with average disease duration of 13.6 years. MS clinical course was reported as relapsing remitting in 78%, secondary progressive in 15%, and primary progressive in 5%. Most patients (72%) were fully ambulatory, 16% could walk with assistance, and 12% were nonambulatory.

Severe COVID-19 outcomes were classified as mortality (which occurred in 5.7% of the cohort), mortality/ICU admission (13.6%) and mortality/ICU admission/hospitalization (30.2%).

Results were adjusted for many different covariates, including sex, age, smoking, MS clinical course (relapsing, progressive), disease duration, ambulation, individual comorbidities (cardiovascular disease, cerebrovascular disease, chronic kidney disease, chronic lung disease, diabetes, hypertension, morbid obesity), and disease-modifying therapy use.

In multivariable logistic regression analyses, older age, having chronic renal disease, and being nonambulatory were consistently associated with increased odds of poorer outcomes. Chronic kidney disease had the strongest association with mortality (odds ratio, 28.6; P < .001). Other factors associated with mortality included cardiovascular disease (OR, 4.35; P = .009); age (OR per 10 years, 1.91; P = .012), and male sex (OR, 2.60; P = .041).

Patients who were nonambulatory had a higher risk of mortality/ICU admission/hospitalization (OR, 3.32; P = .003). This endpoint was also increased in patients on anti-CD20 drugs, compared with other disease-modifying treatment (OR, 2.31; P = .002), consistent with results from at least two other studies.

Disease-modifying therapy in general was not associated with an increased risk of worse outcomes. “There was some concern at the outset about the effect of disease-modifying therapies on COVID-19 outcomes, but most studies have not found an increased risk of worse outcomes in patients on such drug treatments, with the possible exception of anti-CD20 drugs,” Dr. Salter said.

“Some disease-modifying therapies may actually be protective (particularly interferon) and studies are investigating whether they may have a role in the treatment of COVID-19,” she added.

“The factors in MS patients that we and others have found to be associated with worse COVID-19 outcomes may not be specific to MS. Older age is known to be a primary risk factor for worse COVID-19 outcomes in the general population, and increasing disability presumably tracks with worse general heath,” Dr. Salter commented.

“I would say the overall data are fairly reassuring for MS patents,” she concluded.
 

Black patients have higher risk

One worrying finding in the North American data, however, was the effect of race. “We found an independent effect of race for worse COVID-19 outcomes in MS patients,” Dr. Slater said.

Of the 858 patients in the COViMS registry, 65.7% were White and 26.1% were Black. Black individuals were more likely to be younger, never smokers, have shorter MS duration, a relapsing MS course, and have comorbidities, compared with White patients. A higher proportion of Black patients had hypertension (40.2% vs 19.5%) and morbid obesity (17% vs. 9.5%).

Results showed that mortality rates were not statistically different between White and Black patients, but Black race was associated with increased risk of mortality and/or ICU admission, compared with White patients (16.9% vs. 12.8%), and multivariate logistic regression analysis showed Black race was independently associated with mortality/ICU admission after adjustments for covariates (OR, 3.7; P = .002).

Black race was also associated with increased risk of mortality/ICU admission/hospital admission (35.8% vs. 30.2%), and after adjustment for covariates this was found to be an independent predictor (OR, 1.7; P = .04).

“This higher COVID-19 risk in Black individuals is also seen in the general population, so these results are not that surprising and it doesn’t appear to be an effect specific to MS patients,” Dr. Salter commented.
 

U.K. data on risk of contracting COVID-19 

A U.K. study also suggested race to be an independent predictor in the risk of contracting COVID-19 in patients with MS.

The study of more than 5,000 patients with MS showed that those from a Black, Asian, and Minority Ethnic group were twice as likely to report having COVID-19 than those who were White.

The study, which was conducted during the U.K. lockdown, also found that the trend of COVID-19 infection in patients with MS is comparable with that of the U.K. general population.

Presenting the data, Afagh Garjani, MD, concluded: “During a period with strict physical distancing measures, patients with MS are not at an increased risk of contracting COVID-19.”

Dr. Garjani, a neurology clinical research fellow at the University of Nottingham, (England), explained that the COVID-19 pandemic has introduced uncertainties into the MS community, and the focus so far has been the severity of infection among people with MS who have COVID-19.

“This approach has left questions about the risk of contracting disease in people with MS unanswered, which has implications as society gradually returns to normal,” she said.

Dr. Garjani presented data from the United Kingdom MS Register (UKMSR), which has been collecting demographic and MS-related data since 2011 from patients with MS throughout the United Kingdom.

On March 17 – just before the lockdown in United Kingdom – existing participants of the UKMSR were asked to join the COVID-19 study. The study was also advertised through social media. In this ongoing study, people with MS answered a COVID-19–related survey at participation and a different follow-up survey every 2 weeks depending on whether they contracted COVID-19.

The COVID-19 study included 5,309 patients with MS. The mean age of the study population was 52.4 years, 76.1% were female, and 95.7% were White. Of the 5,309 patients, 535 (10%) reported a self-diagnosis of COVID-19. Because of limited availability of tests in the United Kingdom at the time, only 75 patents had a positive polymerase chain reaction result.

“To our knowledge, this is the largest community-based study of COVID-19 in patients with MS worldwide,” Dr. Garjani said. She presented results from the period March 23 to June 24, when the United Kingdom was in a period of lockdown with vulnerable groups encouraged to self-isolate completely.

In this MS cohort, 47% reported self-isolating at some point. Those at older age and higher Expanded Disability Status Scale (EDSS) score were more likely to have self-isolated.

The researchers did not find that patients with progressive MS or those on disease-modifying therapies in general isolated more, but patients on monoclonal antibody drugs and fingolimod were more likely to self-isolate versus those on other therapies. “This may be because there are concerns about infection with these drugs and patients on these therapies may be more concerned about contracting COVID-19,” Dr. Garjani suggested.

In terms of contracting COVID, the researchers found a reduced risk of COVID-19 (self-diagnosed) in patients with older age and higher EDSS. “This is not really surprising that these patients were more likely to self-isolate,” Dr. Garjani commented.

No association was seen between type of MS, disease duration, disease-modifying therapy in general, and risk of COVID-19. No individual drug treatment increased risk versus no therapy or versus self-injectables. But there was an increased risk of contracting the virus in patients whose race was Black, Asian, or Minority Ethnic (OR, 2.2), which is in line with findings from the general population.

“This study is unique – the denominator is all people with MS. We are looking primarily at the risk of contracting COVID-19. Other studies are focusing more on people with MS who have COVID and assessing risk of a severe COVID outcome. Our results are not contradicting the findings from those studies,” Dr. Garjani said.

The results were similar only when patients with a confirmed COVID-19 test were considered.

In terms of outcomes in those who reported COVID-19 infection, preliminary results have not shown any MS factors – such as EDSS, age, type of MS, drug therapy in general – to be associated with outcome.

“Since the COVID-19 outbreak started there has been concern among MS patients, especially among those on disease-modifying therapies, about whether they are at increased risk of infection and severe disease,” Dr. Garjani said.

“We found similar trends of rates of infection in MS patients and the general population, and no signal of increased risks in those with higher EDSS or progressive MS. The caveat is that this study was conducted in a period of lockdown, but we adjusted for self-isolating behavior in the multivariable regression analysis,” she noted.

Dr. Salter is a statistical editor for the American Heart Association journal Circulation: Cardiovascular Imaging. Dr. Garjani has disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.