Key clinical point: In patients with rheumatoid arthritis (RA), baseline magnetic resonance imaging (MRI) osteitis and tenosynovitis independently predicted 2-year MRI damage. Following the MRI-targeted treatment strategy was a positive predictor for stringent remission.

Major finding: Baseline osteitis independently predicted MRI erosion (odds ratio [OR], 1.13), joint space narrowing (OR, 1.15), and combined damage progression (OR, 1.23; P less than .001 for all). Tenosynovitis independently predicted MRI erosion progression (OR, 1.13; P = .01). MRI-targeted treatment strategy predicted Clinical Disease Activity Index remission (OR, 2.94; P = .01), Simplified Disease Activity Index remission (OR, 2.50; P = .047), and Boolean remission (OR, 5.47; P less than .001).

Study details: The data come from the IMAGINE-RA study, a 2-year, investigator-initiated, randomized clinical Danish multicenter trial on 200 RA patients.

Disclosures: The work was supported by AbbVie, who supported the IMAGINE-RA primary study. Some authors received grants/personal fees/nonfinancial support from various research organizations and/or pharmaceutical companies, including AbbVie.

Source: Møller-Bisgaard S et al. Rheumatology (Oxford). 2021 Jan 5. doi: 10.1093/rheumatology/keaa496.

Key clinical point: In patients with rheumatoid arthritis (RA), baseline magnetic resonance imaging (MRI) osteitis and tenosynovitis independently predicted 2-year MRI damage. Following the MRI-targeted treatment strategy was a positive predictor for stringent remission.

Major finding: Baseline osteitis independently predicted MRI erosion (odds ratio [OR], 1.13), joint space narrowing (OR, 1.15), and combined damage progression (OR, 1.23; P less than .001 for all). Tenosynovitis independently predicted MRI erosion progression (OR, 1.13; P = .01). MRI-targeted treatment strategy predicted Clinical Disease Activity Index remission (OR, 2.94; P = .01), Simplified Disease Activity Index remission (OR, 2.50; P = .047), and Boolean remission (OR, 5.47; P less than .001).

Study details: The data come from the IMAGINE-RA study, a 2-year, investigator-initiated, randomized clinical Danish multicenter trial on 200 RA patients.

Disclosures: The work was supported by AbbVie, who supported the IMAGINE-RA primary study. Some authors received grants/personal fees/nonfinancial support from various research organizations and/or pharmaceutical companies, including AbbVie.

Source: Møller-Bisgaard S et al. Rheumatology (Oxford). 2021 Jan 5. doi: 10.1093/rheumatology/keaa496.

Key clinical point: In patients with rheumatoid arthritis (RA), baseline magnetic resonance imaging (MRI) osteitis and tenosynovitis independently predicted 2-year MRI damage. Following the MRI-targeted treatment strategy was a positive predictor for stringent remission.

Major finding: Baseline osteitis independently predicted MRI erosion (odds ratio [OR], 1.13), joint space narrowing (OR, 1.15), and combined damage progression (OR, 1.23; P less than .001 for all). Tenosynovitis independently predicted MRI erosion progression (OR, 1.13; P = .01). MRI-targeted treatment strategy predicted Clinical Disease Activity Index remission (OR, 2.94; P = .01), Simplified Disease Activity Index remission (OR, 2.50; P = .047), and Boolean remission (OR, 5.47; P less than .001).

Study details: The data come from the IMAGINE-RA study, a 2-year, investigator-initiated, randomized clinical Danish multicenter trial on 200 RA patients.

Disclosures: The work was supported by AbbVie, who supported the IMAGINE-RA primary study. Some authors received grants/personal fees/nonfinancial support from various research organizations and/or pharmaceutical companies, including AbbVie.

Source: Møller-Bisgaard S et al. Rheumatology (Oxford). 2021 Jan 5. doi: 10.1093/rheumatology/keaa496.

Key clinical point: Patients with incident rheumatoid arthritis (RA) have increased risks for venous thromboembolism (VTE), pulmonary embolism (PE), and deep vein thrombosis (DVT) than the general population.

Major finding: RA patients showed higher overall risks for VTE (adjusted hazard ratio [aHR], 1.28; 95% confidence interval [CI], 1.20-1.36), PE (aHR, 1.25; 95% CI, 1.13-1.39), and DVT (aHR, 1.30; 95% CI, 1.21-1.40) after adjusting for VTE risk factors.

Study details: The data come from a population-based study involving 39,142 patients with incident RA and 78,078 matched non-RA controls.

Disclosures: The study was supported by the Canadian Institutes of Health Research. The authors declared no conflicts of interest.

Source: Li L et al. Rheumatology (Oxford). 2021 Jan 5. doi: 10.1093/rheumatology/keaa262.

Key clinical point: Patients with incident rheumatoid arthritis (RA) have increased risks for venous thromboembolism (VTE), pulmonary embolism (PE), and deep vein thrombosis (DVT) than the general population.

Major finding: RA patients showed higher overall risks for VTE (adjusted hazard ratio [aHR], 1.28; 95% confidence interval [CI], 1.20-1.36), PE (aHR, 1.25; 95% CI, 1.13-1.39), and DVT (aHR, 1.30; 95% CI, 1.21-1.40) after adjusting for VTE risk factors.

Study details: The data come from a population-based study involving 39,142 patients with incident RA and 78,078 matched non-RA controls.

Disclosures: The study was supported by the Canadian Institutes of Health Research. The authors declared no conflicts of interest.

Source: Li L et al. Rheumatology (Oxford). 2021 Jan 5. doi: 10.1093/rheumatology/keaa262.

Key clinical point: Patients with incident rheumatoid arthritis (RA) have increased risks for venous thromboembolism (VTE), pulmonary embolism (PE), and deep vein thrombosis (DVT) than the general population.

Major finding: RA patients showed higher overall risks for VTE (adjusted hazard ratio [aHR], 1.28; 95% confidence interval [CI], 1.20-1.36), PE (aHR, 1.25; 95% CI, 1.13-1.39), and DVT (aHR, 1.30; 95% CI, 1.21-1.40) after adjusting for VTE risk factors.

Study details: The data come from a population-based study involving 39,142 patients with incident RA and 78,078 matched non-RA controls.

Disclosures: The study was supported by the Canadian Institutes of Health Research. The authors declared no conflicts of interest.

Source: Li L et al. Rheumatology (Oxford). 2021 Jan 5. doi: 10.1093/rheumatology/keaa262.

Key clinical point: Hydroxychloroquine for the treatment of rheumatoid arthritis (RA) does not increase the risks for depression, suicidality, or psychosis compared with sulfasalazine.

Major finding: Hydroxychloroquine use was not associated with risks for depression, acute psychosis, or suicidality compared with sulfasalazine. The hazard ratios [HRs] for short-term risks for depression, acute psychosis, and suicidality were 0.96 (95% confidence interval [CI], 0.79-1.16), 1.03 (95% CI, 0.66-1.60), and 0.94 (95% CI, 0.49-1.77), respectively. The corresponding HRs for long-term risks were 0.94 (95% CI, 0.71-1.26), 0.99 (95% CI, 0.72-1.35), and 0.77 (95% CI, 0.56-1.07), respectively.

Study details: Findings from a multinational network cohort study of RA patients using hydroxychloroquine (n=918,144) and sulfasalazine (n=290,383).

Disclosures: This study was supported by the National Institute for Health Research Oxford Biomedical Research Centre, US National Institutes of Health, US Department of Veterans Affairs, Janssen Research & Development, IQVIA, the Korea Health Technology, and the Korea Health Industry Development Institute. Some of the authors reported personal funding/support from pharmaceutical companies and/or research organizations.

Source: Lane JCE et al. Rheumatology (Oxford). 2020 Dec 25. doi: 10.1093/rheumatology/keaa771.

Key clinical point: Hydroxychloroquine for the treatment of rheumatoid arthritis (RA) does not increase the risks for depression, suicidality, or psychosis compared with sulfasalazine.

Major finding: Hydroxychloroquine use was not associated with risks for depression, acute psychosis, or suicidality compared with sulfasalazine. The hazard ratios [HRs] for short-term risks for depression, acute psychosis, and suicidality were 0.96 (95% confidence interval [CI], 0.79-1.16), 1.03 (95% CI, 0.66-1.60), and 0.94 (95% CI, 0.49-1.77), respectively. The corresponding HRs for long-term risks were 0.94 (95% CI, 0.71-1.26), 0.99 (95% CI, 0.72-1.35), and 0.77 (95% CI, 0.56-1.07), respectively.

Study details: Findings from a multinational network cohort study of RA patients using hydroxychloroquine (n=918,144) and sulfasalazine (n=290,383).

Disclosures: This study was supported by the National Institute for Health Research Oxford Biomedical Research Centre, US National Institutes of Health, US Department of Veterans Affairs, Janssen Research & Development, IQVIA, the Korea Health Technology, and the Korea Health Industry Development Institute. Some of the authors reported personal funding/support from pharmaceutical companies and/or research organizations.

Source: Lane JCE et al. Rheumatology (Oxford). 2020 Dec 25. doi: 10.1093/rheumatology/keaa771.

Key clinical point: Hydroxychloroquine for the treatment of rheumatoid arthritis (RA) does not increase the risks for depression, suicidality, or psychosis compared with sulfasalazine.

Major finding: Hydroxychloroquine use was not associated with risks for depression, acute psychosis, or suicidality compared with sulfasalazine. The hazard ratios [HRs] for short-term risks for depression, acute psychosis, and suicidality were 0.96 (95% confidence interval [CI], 0.79-1.16), 1.03 (95% CI, 0.66-1.60), and 0.94 (95% CI, 0.49-1.77), respectively. The corresponding HRs for long-term risks were 0.94 (95% CI, 0.71-1.26), 0.99 (95% CI, 0.72-1.35), and 0.77 (95% CI, 0.56-1.07), respectively.

Study details: Findings from a multinational network cohort study of RA patients using hydroxychloroquine (n=918,144) and sulfasalazine (n=290,383).

Disclosures: This study was supported by the National Institute for Health Research Oxford Biomedical Research Centre, US National Institutes of Health, US Department of Veterans Affairs, Janssen Research & Development, IQVIA, the Korea Health Technology, and the Korea Health Industry Development Institute. Some of the authors reported personal funding/support from pharmaceutical companies and/or research organizations.

Source: Lane JCE et al. Rheumatology (Oxford). 2020 Dec 25. doi: 10.1093/rheumatology/keaa771.

Key clinical point: Patients with endometriosis are at a significantly higher risk of developing rheumatoid arthritis (RA).

Major finding: The risk of RA was significantly higher in patients with endometriosis (adjusted hazard ratio [aHR], 1.75; 95% confidence interval [CI], 1.27-2.41), those aged 45 years or older (aHR, 1.50; 95% CI, 1.06-2.13), and those with autoimmune disease (aHR, 6.99; 95% CI, 2.84-17.21).

Study details: This 13-year Taiwanese population-based study included 14,463 women with and 14,463 women without endometriosis who were propensity score-matched by age, comorbidities, corticosteroids, nonsteroidal anti-inflammatory drugs, and hormonal medications.

Disclosures: The study was supported by the Chung Shan Medical University’s DryLab Team and grants awarded to Chung Shan Medical University. The authors declared no conflicts of interest.

Source: Xue YH et al. Rheumatology (Oxford). 2020 Dec 17. doi: 10.1093/rheumatology/keaa784.

Key clinical point: Patients with endometriosis are at a significantly higher risk of developing rheumatoid arthritis (RA).

Major finding: The risk of RA was significantly higher in patients with endometriosis (adjusted hazard ratio [aHR], 1.75; 95% confidence interval [CI], 1.27-2.41), those aged 45 years or older (aHR, 1.50; 95% CI, 1.06-2.13), and those with autoimmune disease (aHR, 6.99; 95% CI, 2.84-17.21).

Study details: This 13-year Taiwanese population-based study included 14,463 women with and 14,463 women without endometriosis who were propensity score-matched by age, comorbidities, corticosteroids, nonsteroidal anti-inflammatory drugs, and hormonal medications.

Disclosures: The study was supported by the Chung Shan Medical University’s DryLab Team and grants awarded to Chung Shan Medical University. The authors declared no conflicts of interest.

Source: Xue YH et al. Rheumatology (Oxford). 2020 Dec 17. doi: 10.1093/rheumatology/keaa784.

Key clinical point: Patients with endometriosis are at a significantly higher risk of developing rheumatoid arthritis (RA).

Major finding: The risk of RA was significantly higher in patients with endometriosis (adjusted hazard ratio [aHR], 1.75; 95% confidence interval [CI], 1.27-2.41), those aged 45 years or older (aHR, 1.50; 95% CI, 1.06-2.13), and those with autoimmune disease (aHR, 6.99; 95% CI, 2.84-17.21).

Study details: This 13-year Taiwanese population-based study included 14,463 women with and 14,463 women without endometriosis who were propensity score-matched by age, comorbidities, corticosteroids, nonsteroidal anti-inflammatory drugs, and hormonal medications.

Disclosures: The study was supported by the Chung Shan Medical University’s DryLab Team and grants awarded to Chung Shan Medical University. The authors declared no conflicts of interest.

Source: Xue YH et al. Rheumatology (Oxford). 2020 Dec 17. doi: 10.1093/rheumatology/keaa784.

Key clinical point: In patients with active rheumatoid arthritis (RA) who had limited or no prior methotrexate (MTX) exposure, filgotinib (FIL) with MTX reduced signs and symptoms of RA and improved physical function with an acceptable safety profile up to 52 weeks.

Major finding: At week 24, significantly higher proportions of patients receiving FIL200 + MTX (81%; P less than .001) and FIL100 + MTX (80%; P = .017) achieved 20% improvement in American College of Rheumatology criteria (ACR20) vs. MTX (71%). Significant improvements in Health Assessment Questionnaire-Disability Index and 28-joint Disease Activity Score with C-reactive protein less than 2.6 were seen at week 24. Adverse event rates through week 52 were comparable between all treatments.

Study details: In this 52-week phase 3 FINCH 3 trial, 1,252 patients with RA were randomly assigned in a 2:1:1:2 ratio to receive filgotinib 200 mg with MTX (FIL200 + MTX), filgotinib 100 mg with MTX (FIL100+MTX), filgotinib 200 mg monotherapy (FIL200), or MTX.

Disclosures: The study was funded by Gilead Sciences, Inc. The lead author reported receiving grant/research support from and serving as a consultant for Celltrion, Galapagos, and Gilead Sciences.

Source: Westhovens R et al. Ann Rheum Dis. 2021 Jan 15. doi: 10.1136/annrheumdis-2020-219213.

Key clinical point: In patients with active rheumatoid arthritis (RA) who had limited or no prior methotrexate (MTX) exposure, filgotinib (FIL) with MTX reduced signs and symptoms of RA and improved physical function with an acceptable safety profile up to 52 weeks.

Major finding: At week 24, significantly higher proportions of patients receiving FIL200 + MTX (81%; P less than .001) and FIL100 + MTX (80%; P = .017) achieved 20% improvement in American College of Rheumatology criteria (ACR20) vs. MTX (71%). Significant improvements in Health Assessment Questionnaire-Disability Index and 28-joint Disease Activity Score with C-reactive protein less than 2.6 were seen at week 24. Adverse event rates through week 52 were comparable between all treatments.

Study details: In this 52-week phase 3 FINCH 3 trial, 1,252 patients with RA were randomly assigned in a 2:1:1:2 ratio to receive filgotinib 200 mg with MTX (FIL200 + MTX), filgotinib 100 mg with MTX (FIL100+MTX), filgotinib 200 mg monotherapy (FIL200), or MTX.

Disclosures: The study was funded by Gilead Sciences, Inc. The lead author reported receiving grant/research support from and serving as a consultant for Celltrion, Galapagos, and Gilead Sciences.

Source: Westhovens R et al. Ann Rheum Dis. 2021 Jan 15. doi: 10.1136/annrheumdis-2020-219213.

Key clinical point: In patients with active rheumatoid arthritis (RA) who had limited or no prior methotrexate (MTX) exposure, filgotinib (FIL) with MTX reduced signs and symptoms of RA and improved physical function with an acceptable safety profile up to 52 weeks.

Major finding: At week 24, significantly higher proportions of patients receiving FIL200 + MTX (81%; P less than .001) and FIL100 + MTX (80%; P = .017) achieved 20% improvement in American College of Rheumatology criteria (ACR20) vs. MTX (71%). Significant improvements in Health Assessment Questionnaire-Disability Index and 28-joint Disease Activity Score with C-reactive protein less than 2.6 were seen at week 24. Adverse event rates through week 52 were comparable between all treatments.

Study details: In this 52-week phase 3 FINCH 3 trial, 1,252 patients with RA were randomly assigned in a 2:1:1:2 ratio to receive filgotinib 200 mg with MTX (FIL200 + MTX), filgotinib 100 mg with MTX (FIL100+MTX), filgotinib 200 mg monotherapy (FIL200), or MTX.

Disclosures: The study was funded by Gilead Sciences, Inc. The lead author reported receiving grant/research support from and serving as a consultant for Celltrion, Galapagos, and Gilead Sciences.

Source: Westhovens R et al. Ann Rheum Dis. 2021 Jan 15. doi: 10.1136/annrheumdis-2020-219213.

Key clinical point: Cardiovascular (CV) disease (CVD) and CV risk factors were risk factors for incident dementia among rheumatoid arthritis (RA) patients between 65 and 74 years of age; however, this risk attenuated with increasing age.

Major finding: Patients with CVD and CV risk factors between 65 and 74 years of age had an increased risk for dementia vs. those without CVD and CV risk factors (adjusted hazard Ratio [aHR], 1.18; 95% confidence interval [CI], 1.04-1.33; aHR, 1.03; 95% CI, 1.00-1.11, respectively). For patients between 75 and 84 years of age, a trend toward an increased risk of dementia was observed with CVD but was not statistically significant (aHR, 1.03; 95% CI, 0.92-1.14). These associations were not observed among patients aged 85 years and older.

Study details: Longitudinal analysis of 56,567 patients with RA using Center for Medicare & Medicaid claims (CMS) data from 2006 to 2014; 11,789 (20.1%) incident cases of dementia were included in the analysis.

Disclosures: The study was supported by I Navarro-Millan’s IPCI award from Weill Cornell Medicine Division of General Internal Medicine. JR Curtis received research support and consulting fees from AbbVie, Amgen, BMS, Corrona, Eli Lilly, Janssen, Myriad, Pfizer, Regeneron, Roche, and UCB. SB Lieber reported spousal ownership interests in Cigna, Intuitive Surgical, Inc., Merck, and Pfizer. I Navarro-Millán received consulting fees from Sobi. The remaining authors declared no conflicts of interest.

Source: Sattui SE et al. Semin Arthritis Rheum. 2021 Jan 5. doi: 10.1016/j.semarthrit.2020.09.022.

Key clinical point: Cardiovascular (CV) disease (CVD) and CV risk factors were risk factors for incident dementia among rheumatoid arthritis (RA) patients between 65 and 74 years of age; however, this risk attenuated with increasing age.

Major finding: Patients with CVD and CV risk factors between 65 and 74 years of age had an increased risk for dementia vs. those without CVD and CV risk factors (adjusted hazard Ratio [aHR], 1.18; 95% confidence interval [CI], 1.04-1.33; aHR, 1.03; 95% CI, 1.00-1.11, respectively). For patients between 75 and 84 years of age, a trend toward an increased risk of dementia was observed with CVD but was not statistically significant (aHR, 1.03; 95% CI, 0.92-1.14). These associations were not observed among patients aged 85 years and older.

Study details: Longitudinal analysis of 56,567 patients with RA using Center for Medicare & Medicaid claims (CMS) data from 2006 to 2014; 11,789 (20.1%) incident cases of dementia were included in the analysis.

Disclosures: The study was supported by I Navarro-Millan’s IPCI award from Weill Cornell Medicine Division of General Internal Medicine. JR Curtis received research support and consulting fees from AbbVie, Amgen, BMS, Corrona, Eli Lilly, Janssen, Myriad, Pfizer, Regeneron, Roche, and UCB. SB Lieber reported spousal ownership interests in Cigna, Intuitive Surgical, Inc., Merck, and Pfizer. I Navarro-Millán received consulting fees from Sobi. The remaining authors declared no conflicts of interest.

Source: Sattui SE et al. Semin Arthritis Rheum. 2021 Jan 5. doi: 10.1016/j.semarthrit.2020.09.022.

Key clinical point: Cardiovascular (CV) disease (CVD) and CV risk factors were risk factors for incident dementia among rheumatoid arthritis (RA) patients between 65 and 74 years of age; however, this risk attenuated with increasing age.

Major finding: Patients with CVD and CV risk factors between 65 and 74 years of age had an increased risk for dementia vs. those without CVD and CV risk factors (adjusted hazard Ratio [aHR], 1.18; 95% confidence interval [CI], 1.04-1.33; aHR, 1.03; 95% CI, 1.00-1.11, respectively). For patients between 75 and 84 years of age, a trend toward an increased risk of dementia was observed with CVD but was not statistically significant (aHR, 1.03; 95% CI, 0.92-1.14). These associations were not observed among patients aged 85 years and older.

Study details: Longitudinal analysis of 56,567 patients with RA using Center for Medicare & Medicaid claims (CMS) data from 2006 to 2014; 11,789 (20.1%) incident cases of dementia were included in the analysis.

Disclosures: The study was supported by I Navarro-Millan’s IPCI award from Weill Cornell Medicine Division of General Internal Medicine. JR Curtis received research support and consulting fees from AbbVie, Amgen, BMS, Corrona, Eli Lilly, Janssen, Myriad, Pfizer, Regeneron, Roche, and UCB. SB Lieber reported spousal ownership interests in Cigna, Intuitive Surgical, Inc., Merck, and Pfizer. I Navarro-Millán received consulting fees from Sobi. The remaining authors declared no conflicts of interest.

Source: Sattui SE et al. Semin Arthritis Rheum. 2021 Jan 5. doi: 10.1016/j.semarthrit.2020.09.022.

Key clinical point: Higher disease activity and elevated levels of cytokines/chemokines are associated with a greater risk of diabetes mellitus (DM) in patients with rheumatoid arthritis (RA).

Major finding: High Disease activity Score (DAS28)-C reactive protein (CRP) was associated with an increased risk of DM (test for trend: P less than .001). Several cytokines/chemokines analyzed showed independent association with DM risk including interleukin (IL)-1, IL-6, and select macrophage-derived cytokines/chemokines (hazard ratio per standard deviation range, 1.11-1.26). These associations were independent of the DAS28-CRP.

Study details: This longitudinal analysis included 1,866 patients with RA without prevalent DM from Veteran’s Affairs Rheumatoid Arthritis Registry. Thirty cytokines and chemokines were measured in banked serum obtained at the time of enrolment.

Disclosures: No study sponsor was identified. The presenting author has received consulting fees from Bristol-Myers Squibb and Gilead.

Source: Baker JF. Ann Rheum Dis. 2021 Jan 4. doi: 10.1136/annrheumdis-2020-219140

Key clinical point: Higher disease activity and elevated levels of cytokines/chemokines are associated with a greater risk of diabetes mellitus (DM) in patients with rheumatoid arthritis (RA).

Major finding: High Disease activity Score (DAS28)-C reactive protein (CRP) was associated with an increased risk of DM (test for trend: P less than .001). Several cytokines/chemokines analyzed showed independent association with DM risk including interleukin (IL)-1, IL-6, and select macrophage-derived cytokines/chemokines (hazard ratio per standard deviation range, 1.11-1.26). These associations were independent of the DAS28-CRP.

Study details: This longitudinal analysis included 1,866 patients with RA without prevalent DM from Veteran’s Affairs Rheumatoid Arthritis Registry. Thirty cytokines and chemokines were measured in banked serum obtained at the time of enrolment.

Disclosures: No study sponsor was identified. The presenting author has received consulting fees from Bristol-Myers Squibb and Gilead.

Source: Baker JF. Ann Rheum Dis. 2021 Jan 4. doi: 10.1136/annrheumdis-2020-219140

Key clinical point: Higher disease activity and elevated levels of cytokines/chemokines are associated with a greater risk of diabetes mellitus (DM) in patients with rheumatoid arthritis (RA).

Major finding: High Disease activity Score (DAS28)-C reactive protein (CRP) was associated with an increased risk of DM (test for trend: P less than .001). Several cytokines/chemokines analyzed showed independent association with DM risk including interleukin (IL)-1, IL-6, and select macrophage-derived cytokines/chemokines (hazard ratio per standard deviation range, 1.11-1.26). These associations were independent of the DAS28-CRP.

Study details: This longitudinal analysis included 1,866 patients with RA without prevalent DM from Veteran’s Affairs Rheumatoid Arthritis Registry. Thirty cytokines and chemokines were measured in banked serum obtained at the time of enrolment.

Disclosures: No study sponsor was identified. The presenting author has received consulting fees from Bristol-Myers Squibb and Gilead.

Source: Baker JF. Ann Rheum Dis. 2021 Jan 4. doi: 10.1136/annrheumdis-2020-219140

Key clinical point: Use of hydroxychloroquine (HCQ) is not associated with increased risk of developing heart failure (HF) in patients with rheumatoid arthritis (RA).

Major finding: HCQ cumulative dose was not associated with HF (odds ratio [OR], 0.96 [95% confidence interval (CI), 0.90-1.03] per 100 g). No statistically significant association was found for patients with a cumulative dose of 300 g or more (OR, 0.92; 95% CI, 0.41-2.08). Duration of HCQ use prior to index was not associated with HF (OR, 0.98; 95% CI, 0.91-1.05).

Study details: The data come from a nested case-control study of 143 RA cases diagnosed with HF and 143 non-HF RA controls.

Disclosures: The study was funded by grants from the National Institutes of Health. The authors declared no conflicts of interest.

Source: Sorour AA et al. J Rheumatol. 2021 Jan 15. doi: 10.3899/jrheum.201180

Key clinical point: Use of hydroxychloroquine (HCQ) is not associated with increased risk of developing heart failure (HF) in patients with rheumatoid arthritis (RA).

Major finding: HCQ cumulative dose was not associated with HF (odds ratio [OR], 0.96 [95% confidence interval (CI), 0.90-1.03] per 100 g). No statistically significant association was found for patients with a cumulative dose of 300 g or more (OR, 0.92; 95% CI, 0.41-2.08). Duration of HCQ use prior to index was not associated with HF (OR, 0.98; 95% CI, 0.91-1.05).

Study details: The data come from a nested case-control study of 143 RA cases diagnosed with HF and 143 non-HF RA controls.

Disclosures: The study was funded by grants from the National Institutes of Health. The authors declared no conflicts of interest.

Source: Sorour AA et al. J Rheumatol. 2021 Jan 15. doi: 10.3899/jrheum.201180

Key clinical point: Use of hydroxychloroquine (HCQ) is not associated with increased risk of developing heart failure (HF) in patients with rheumatoid arthritis (RA).

Major finding: HCQ cumulative dose was not associated with HF (odds ratio [OR], 0.96 [95% confidence interval (CI), 0.90-1.03] per 100 g). No statistically significant association was found for patients with a cumulative dose of 300 g or more (OR, 0.92; 95% CI, 0.41-2.08). Duration of HCQ use prior to index was not associated with HF (OR, 0.98; 95% CI, 0.91-1.05).

Study details: The data come from a nested case-control study of 143 RA cases diagnosed with HF and 143 non-HF RA controls.

Disclosures: The study was funded by grants from the National Institutes of Health. The authors declared no conflicts of interest.

Source: Sorour AA et al. J Rheumatol. 2021 Jan 15. doi: 10.3899/jrheum.201180

Women who’ve had gestational diabetes are 40% more likely to develop coronary artery calcification later in life than are women haven’t, and attaining normal glycemic levels doesn’t diminish their midlife risk for atherosclerotic cardiovascular disease.

“The new finding from this study is that women with gestational diabetes had twice the risk of coronary artery calcium, compared to women who never had gestational diabetes, even though both groups attained normal blood sugar levels many years after pregnancy,” lead author Erica P. Gunderson, PhD, MS, MPH, said in an interview about a community-based prospective cohort study of young adults followed for up to 25 years, which was published in Circulation (2021 Feb 1. doi: 10.1161/CIRCULATIONAHA.120.047320).

Previous studies have reported a higher risk of heart disease in women who had gestational diabetes (GD) and later developed type 2 diabetes, but they didn’t elucidate whether that risk carried over in GD patients whose glycemic levels were normal after pregnancy. In 2018, the American College of Cardiology/American Heart Association Cholesterol Clinical Practice Guidelines specified that a history of GD increases women’s risk for coronary artery calcification (CAC).

This study analyzed data of 1,133 women ages 18-30 enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study who had no diabetes in the baseline years of 1985-1986 and had given birth at least once in the ensuing 25 years. They had glucose tolerance testing at baseline and up to five times through the study period, along with evaluation for GD status and coronary artery calcification CAC measurements at least once at years 15, 20 and 25 (2001-2011).

CARDIA enrolled 5,155 young Black and White men and women ages 18-30 from four distinct geographic areas: Birmingham, Ala.; Chicago; Minneapolis; and Oakland, Calif. About 52% of the study population was Black.

Of the women who’d given birth, 139 (12%) had GD. Their average age at follow-up was 47.6 years, and 25% of the GD patients (34) had CAC, compared with 15% (149/994) in the non-GD group.

Dr. Gunderson noted that the same relative risk for CAC applied to women who had GD and went on to develop prediabetes or were diagnosed with type 2 diabetes during follow-up.
 

Risks persist even in normoglycemia

In the GD group, the adjusted hazard ratio for having CAC with normoglycemia was 2.3 (95% confidence interval, 1.34-4.09). The researchers also calculated HRs for prediabetes and incident diabetes: 1.5 (95% CI, 1.06-2.24) in no-GD and 2.1 (95% CI, 1.09-4.17) for GD for prediabetes; and 2.2 (95% CI, 1.3-3.62) and 2.02 (95% CI, 0.98-4.19), respectively, for incident diabetes (P = .003).

“This means the risk of heart disease may be increased substantially in women with a history of gestational diabetes and may not diminish even if their blood-sugar levels remain normal for years later,” said Dr. Gunderson, an epidemiologist and senior research scientist at the Kaiser Permanente Northern California Division of Research in Oakland.

“The clinical implications of our findings are that women with previous GD may benefit from enhanced traditional CVD [cardiovascular disease] risk factor testing – i.e., for hypertension, dyslipidemia, and hyperinsulinemia,” Dr. Gunderson said. “Our findings also suggest that it could be beneficial to incorporate history of GD into risk calculators to improve CVD risk stratification and prevention.”
 

Strong findings argue for more frequent CVD screening

These study results may be the strongest data to date on the long-term effects of GD, said Prakash Deedwania, MD, professor of cardiology at the University of California, San Francisco. “It’s the strongest in the sense in that it’s sponsored, involved four different communities in different parts of the United States, enrolled individuals when they were young and followed them, and saw very few patients drop out for such a long-term study.” The study reported follow-up data on 72% of patients at 25 years, a rate Dr. Deedwania noted was “excellent.”

“Patients who have had GD should be screened aggressively – for not only diabetes, but other cardiovascular risk factors – early on to minimize the subsequent risk of cardiovascular disease is a very important point of this study,” he added. In the absence of a clinical guideline, Dr. Deedwania suggested women with GD might have screening for CV risk factors every 5-7 years depending on their risk profile, but emphasized that parameter isn’t settled.

Future research should focus on the link between GD and CVD risk, Dr. Gunderson said. “Research is needed to better characterize the severity of GD in relation to CVD outcomes, and to identify critical pregnancy-related periods to modify cardiometabolic risk.” The latter would include life-course studies across the full pregnancy continuum from preconception to lactation. “Interventions for primary prevention of CVD and the importance of modifiable lifestyle behaviors with the highest relevance to reduce both diabetes and CVD risks during the first year post partum merit increased research investigation,” she added.

Future studies might also explore the role of inflammation in the GD-CVD relationship, Dr. Deedwania said. “My hypothesis is, and it’s purely a hypothesis, that perhaps the presence of coronary artery calcification scores score in these individuals who were described as having normal glucose but who could be at risk could very well be related to the beginning of inflammation.”

Dr. Gunderson and Dr. Deedwania have no financial relationships to disclose. The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Heart, Lung, and Blood Institute.

Women who’ve had gestational diabetes are 40% more likely to develop coronary artery calcification later in life than are women haven’t, and attaining normal glycemic levels doesn’t diminish their midlife risk for atherosclerotic cardiovascular disease.

“The new finding from this study is that women with gestational diabetes had twice the risk of coronary artery calcium, compared to women who never had gestational diabetes, even though both groups attained normal blood sugar levels many years after pregnancy,” lead author Erica P. Gunderson, PhD, MS, MPH, said in an interview about a community-based prospective cohort study of young adults followed for up to 25 years, which was published in Circulation (2021 Feb 1. doi: 10.1161/CIRCULATIONAHA.120.047320).

Previous studies have reported a higher risk of heart disease in women who had gestational diabetes (GD) and later developed type 2 diabetes, but they didn’t elucidate whether that risk carried over in GD patients whose glycemic levels were normal after pregnancy. In 2018, the American College of Cardiology/American Heart Association Cholesterol Clinical Practice Guidelines specified that a history of GD increases women’s risk for coronary artery calcification (CAC).

This study analyzed data of 1,133 women ages 18-30 enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study who had no diabetes in the baseline years of 1985-1986 and had given birth at least once in the ensuing 25 years. They had glucose tolerance testing at baseline and up to five times through the study period, along with evaluation for GD status and coronary artery calcification CAC measurements at least once at years 15, 20 and 25 (2001-2011).

CARDIA enrolled 5,155 young Black and White men and women ages 18-30 from four distinct geographic areas: Birmingham, Ala.; Chicago; Minneapolis; and Oakland, Calif. About 52% of the study population was Black.

Of the women who’d given birth, 139 (12%) had GD. Their average age at follow-up was 47.6 years, and 25% of the GD patients (34) had CAC, compared with 15% (149/994) in the non-GD group.

Dr. Gunderson noted that the same relative risk for CAC applied to women who had GD and went on to develop prediabetes or were diagnosed with type 2 diabetes during follow-up.
 

Risks persist even in normoglycemia

In the GD group, the adjusted hazard ratio for having CAC with normoglycemia was 2.3 (95% confidence interval, 1.34-4.09). The researchers also calculated HRs for prediabetes and incident diabetes: 1.5 (95% CI, 1.06-2.24) in no-GD and 2.1 (95% CI, 1.09-4.17) for GD for prediabetes; and 2.2 (95% CI, 1.3-3.62) and 2.02 (95% CI, 0.98-4.19), respectively, for incident diabetes (P = .003).

“This means the risk of heart disease may be increased substantially in women with a history of gestational diabetes and may not diminish even if their blood-sugar levels remain normal for years later,” said Dr. Gunderson, an epidemiologist and senior research scientist at the Kaiser Permanente Northern California Division of Research in Oakland.

“The clinical implications of our findings are that women with previous GD may benefit from enhanced traditional CVD [cardiovascular disease] risk factor testing – i.e., for hypertension, dyslipidemia, and hyperinsulinemia,” Dr. Gunderson said. “Our findings also suggest that it could be beneficial to incorporate history of GD into risk calculators to improve CVD risk stratification and prevention.”
 

Strong findings argue for more frequent CVD screening

These study results may be the strongest data to date on the long-term effects of GD, said Prakash Deedwania, MD, professor of cardiology at the University of California, San Francisco. “It’s the strongest in the sense in that it’s sponsored, involved four different communities in different parts of the United States, enrolled individuals when they were young and followed them, and saw very few patients drop out for such a long-term study.” The study reported follow-up data on 72% of patients at 25 years, a rate Dr. Deedwania noted was “excellent.”

“Patients who have had GD should be screened aggressively – for not only diabetes, but other cardiovascular risk factors – early on to minimize the subsequent risk of cardiovascular disease is a very important point of this study,” he added. In the absence of a clinical guideline, Dr. Deedwania suggested women with GD might have screening for CV risk factors every 5-7 years depending on their risk profile, but emphasized that parameter isn’t settled.

Future research should focus on the link between GD and CVD risk, Dr. Gunderson said. “Research is needed to better characterize the severity of GD in relation to CVD outcomes, and to identify critical pregnancy-related periods to modify cardiometabolic risk.” The latter would include life-course studies across the full pregnancy continuum from preconception to lactation. “Interventions for primary prevention of CVD and the importance of modifiable lifestyle behaviors with the highest relevance to reduce both diabetes and CVD risks during the first year post partum merit increased research investigation,” she added.

Future studies might also explore the role of inflammation in the GD-CVD relationship, Dr. Deedwania said. “My hypothesis is, and it’s purely a hypothesis, that perhaps the presence of coronary artery calcification scores score in these individuals who were described as having normal glucose but who could be at risk could very well be related to the beginning of inflammation.”

Dr. Gunderson and Dr. Deedwania have no financial relationships to disclose. The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Heart, Lung, and Blood Institute.

Women who’ve had gestational diabetes are 40% more likely to develop coronary artery calcification later in life than are women haven’t, and attaining normal glycemic levels doesn’t diminish their midlife risk for atherosclerotic cardiovascular disease.

“The new finding from this study is that women with gestational diabetes had twice the risk of coronary artery calcium, compared to women who never had gestational diabetes, even though both groups attained normal blood sugar levels many years after pregnancy,” lead author Erica P. Gunderson, PhD, MS, MPH, said in an interview about a community-based prospective cohort study of young adults followed for up to 25 years, which was published in Circulation (2021 Feb 1. doi: 10.1161/CIRCULATIONAHA.120.047320).

Previous studies have reported a higher risk of heart disease in women who had gestational diabetes (GD) and later developed type 2 diabetes, but they didn’t elucidate whether that risk carried over in GD patients whose glycemic levels were normal after pregnancy. In 2018, the American College of Cardiology/American Heart Association Cholesterol Clinical Practice Guidelines specified that a history of GD increases women’s risk for coronary artery calcification (CAC).

This study analyzed data of 1,133 women ages 18-30 enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study who had no diabetes in the baseline years of 1985-1986 and had given birth at least once in the ensuing 25 years. They had glucose tolerance testing at baseline and up to five times through the study period, along with evaluation for GD status and coronary artery calcification CAC measurements at least once at years 15, 20 and 25 (2001-2011).

CARDIA enrolled 5,155 young Black and White men and women ages 18-30 from four distinct geographic areas: Birmingham, Ala.; Chicago; Minneapolis; and Oakland, Calif. About 52% of the study population was Black.

Of the women who’d given birth, 139 (12%) had GD. Their average age at follow-up was 47.6 years, and 25% of the GD patients (34) had CAC, compared with 15% (149/994) in the non-GD group.

Dr. Gunderson noted that the same relative risk for CAC applied to women who had GD and went on to develop prediabetes or were diagnosed with type 2 diabetes during follow-up.
 

Risks persist even in normoglycemia

In the GD group, the adjusted hazard ratio for having CAC with normoglycemia was 2.3 (95% confidence interval, 1.34-4.09). The researchers also calculated HRs for prediabetes and incident diabetes: 1.5 (95% CI, 1.06-2.24) in no-GD and 2.1 (95% CI, 1.09-4.17) for GD for prediabetes; and 2.2 (95% CI, 1.3-3.62) and 2.02 (95% CI, 0.98-4.19), respectively, for incident diabetes (P = .003).

“This means the risk of heart disease may be increased substantially in women with a history of gestational diabetes and may not diminish even if their blood-sugar levels remain normal for years later,” said Dr. Gunderson, an epidemiologist and senior research scientist at the Kaiser Permanente Northern California Division of Research in Oakland.

“The clinical implications of our findings are that women with previous GD may benefit from enhanced traditional CVD [cardiovascular disease] risk factor testing – i.e., for hypertension, dyslipidemia, and hyperinsulinemia,” Dr. Gunderson said. “Our findings also suggest that it could be beneficial to incorporate history of GD into risk calculators to improve CVD risk stratification and prevention.”
 

Strong findings argue for more frequent CVD screening

These study results may be the strongest data to date on the long-term effects of GD, said Prakash Deedwania, MD, professor of cardiology at the University of California, San Francisco. “It’s the strongest in the sense in that it’s sponsored, involved four different communities in different parts of the United States, enrolled individuals when they were young and followed them, and saw very few patients drop out for such a long-term study.” The study reported follow-up data on 72% of patients at 25 years, a rate Dr. Deedwania noted was “excellent.”

“Patients who have had GD should be screened aggressively – for not only diabetes, but other cardiovascular risk factors – early on to minimize the subsequent risk of cardiovascular disease is a very important point of this study,” he added. In the absence of a clinical guideline, Dr. Deedwania suggested women with GD might have screening for CV risk factors every 5-7 years depending on their risk profile, but emphasized that parameter isn’t settled.

Future research should focus on the link between GD and CVD risk, Dr. Gunderson said. “Research is needed to better characterize the severity of GD in relation to CVD outcomes, and to identify critical pregnancy-related periods to modify cardiometabolic risk.” The latter would include life-course studies across the full pregnancy continuum from preconception to lactation. “Interventions for primary prevention of CVD and the importance of modifiable lifestyle behaviors with the highest relevance to reduce both diabetes and CVD risks during the first year post partum merit increased research investigation,” she added.

Future studies might also explore the role of inflammation in the GD-CVD relationship, Dr. Deedwania said. “My hypothesis is, and it’s purely a hypothesis, that perhaps the presence of coronary artery calcification scores score in these individuals who were described as having normal glucose but who could be at risk could very well be related to the beginning of inflammation.”

Dr. Gunderson and Dr. Deedwania have no financial relationships to disclose. The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Heart, Lung, and Blood Institute.

Long-acting injectable antipsychotics (LAIs) are an essential tool in the treatment of patients with psychotic disorders, allowing for periods of stable drug plasma concentration and confirmed adherence.¹ The current coronavirus disease 2019 (COVID-19) pandemic presents unique challenges for administering LAIs and requires a thoughtful and prospective approach in order to ensure continuity of psychiatric care while minimizing the risk of infection with COVID-19. Ideally, patients should be seen in person as infrequently as clinically prudent during this public health emergency; however, LAI administration necessitates direct physical contact between patient and clinician.

Patients with serious mental illness (SMI), who comprise the majority of individuals who receive LAIs, are at heightened risk for cardiovascular and pulmonary comorbidities. These factors are the primary reason the life expectancy of a patient with SMI is nearly 30 years shorter than that of the general population.^2-5 The risk of health care workers becoming infected or inadvertently spreading COVID-19 is heightened when working with patients in group living environments (ie, a shelter or group home), who have both increased exposure and increased risk of further transmission.⁶ Additional patient populations, including older adults, immunocompromised individuals, and those with preexisting conditions, are at heightened risk for serious complications if they were to contract COVID-19.^7,8

Thus, the questions of whether LAIs should be administered, and how to do so safely (both during the ongoing, acute phase of the pandemic as well as during the subsequent recovery period until the pandemic abates) need to be carefully considered. In this article, we provide concrete advice for clinicians and clinics on these topics, with the goal of maintaining patients’ psychiatric stability while protecting patients, health care workers, and the broader society from COVID-19 infection. Table 1 summarizes the questions regarding LAIs that clinicians need to address during this crisis. While we focus on outpatient care, inpatient teams should keep these considerations in mind if they are starting and discharging a patient on an LAI. More than ever, close collaboration and communication between inpatient and outpatient teams is critical.

Should an LAI be continued?

An important first step to approaching this challenge is to create a spreadsheet for all patients receiving LAIs. Focusing on a population-based approach is helpful to be systematic and ensure that no patients fall through the cracks during this public health emergency.⁹ Once all patients have been identified, the treatment team should review each patient to determine if continuing to administer the antipsychotic as an LAI formulation is essential, taking into account the patient’s current psychiatric status, historical medication adherence, potential severity and dangerousness of decompensation if nonadherent, and structures to support stability. For example, can a patient move in with family who can monitor medication adherence during the pandemic? Is it possible for the group home to assume medication administration? Additional consideration should be given to the living environment and health-vulnerability of the patient and the individuals living with them.

If the risk calculation does not point strongly towards a need for continuing the LAI, it may be prudent to temporarily transition the patient to the corresponding oral antipsychotic preparation. Table 2 lists all LAIs available in the United States and their approximate equivalent oral dosing. It is important to note that such transitions are not without clinical risk, to emphasize to the patient that the transition is intended as a temporary measure, and to discuss a proposed timeline for re-initiating the LAI. Also, emphasize to the patient and family that this transition does not diminish the previous reasoning for needing an LAI, but is a temporary measure taken in light of weighing the risks and benefits during a pandemic.

Which LAI should be administered?

If continuing the LAI is determined to be clinically necessary, consider switching the patient to a longer-acting preparation to maximize intervals between administrations and minimize the potential for infection. From a public health perspective, the longest clinically prudent interval between injections may be the most important consideration, provided the patient can receive a dose necessary to retain stability, and the LAI should be chosen accordingly. Deltoid injections may be able to be administered with reduced contact, or on a “drive-up” basis.¹⁰ Consider transitioning a patient who is receiving olanzapine pamoate to an alternate LAI or oral formulation, because the 3-hour observation period that is required after olanzapine pamoate administration is particularly problematic. While it may not be ideal to make medication changes during a pandemic, it is worth carefully weighing the patient’s stability and historical experience with other LAIs to determine if a safer/longer-spaced option is worth trying.¹¹

We recommend only switching among similar antipsychotics (ie, risperidone to paliperidone), or between different preparations of the same drug (ie, Abilify Maintena to Aristada), if possible, as these are the lowest risk transitions with regards to relapse. Table 3 provides examples.

Continue to: When should the LAI be administered?

The pharmacokinetics of LAIs allow for some flexibility in terms of when an LAI needs to be administered. The package inserts of all second-generation LAIs include missed-dose guidelines. These guidelines provide information on how long one can wait before the next injection is due, and what additional measures must be taken when beyond that date. Delaying an injection may be prudent, and the missed dose guidelines will indicate when one must consider supplementing with oral medications. For patients who are in quarantine, it may be better to delay an injection until the patient ends their quarantine than to deliver the dose during quarantine. Administering an injection earlier also is usually safe; off-cycle visits may help minimize patient contact (ie, if the patient happens to be coming into the vicinity of the clinic, or requires phlebotomy for therapeutic drug monitoring), and assist in planning for possible resurgences. When appropriate, and after considering the risk of worsening adverse effects, administering a higher dose than the usual maintenance dose would provide a buffer if the next injection was to be delayed. Therapeutic drug monitoring can help to optimize dosing and avoid low plasma drug levels, which may be not be sufficient, particularly during this time of stress.¹² To provide optimal protection against relapse, consider administering a dose that puts patients at the higher range of plasma drug levels.

Where can the LAI be administered, and who can give it?

For patients who usually travel to a clinic, consider arranging for a more local injection (ie, at the patient’s primary care clinic in their hometown, or at a local mental health center), and explore if the patient may be able to receive their injection in their home through a visiting nurse association (VNA). In many states (approximately 30 currently), clinicians at pharmacies are also able to administer patient injections. Clinics would do well to at least plan for alternate staffing models in the event of staff illness. A pool of individuals should be available to give injections; consider training additional staff members (including MDs who may have never previously administered an LAI but could be quickly instructed to do so) to administer LAIs. Theoretically, during a public health emergency, family members, particularly those who have a background in health care, could be trained to give an injection and provided education on LAI storage and post-injection monitoring. This approach would not be consistent with FDA labeling, however, and should only be considered as a last resort.

What safety measures can be put in place?

Face-to-face time for injection administration should be kept as brief as possible. Before the encounter, obtain the patient’s clinical information, ideally through telehealth or from an acceptable distance. Medication should be drawn ahead of time, and not in an enclosed space with the patient present. Strongly consider abandoning the traditional enclosed room for the injection, and instead use larger spaces, doorways, or outside, if feasible. As previously noted, some clinics and clinicians have used a drive-up approach for LAI administration, particularly for deltoid injections.¹⁰ Individuals who administer the injections should wear personal protective equipment, and the clinic should obtain an adequate supply of this equipment well in advance.

Lessons learned at our clinic

In our community mental health center clinic, planning around these questions has allowed us to provide safe and continuous psychiatric care with LAIs during this public health emergency while reducing the risk of infection. We have worked to transfer LAI administration to VNAs and transition patients to longer-lasting formulations or oral medications where appropriate, which has resulted in an approximately 50% decrease in in-person visits. Reducing the number of in-person visits does not need to result in less frequent clinical follow-up. Telepsychiatry visits can make up for lost in-person visits and have generally been well accepted.

As we are preparing for the next phase, routine medical health monitoring (eg, metabolic monitoring, monitoring for tardive dyskinesia) that has not been at the forefront of concerns should be carefully reintroduced. Challenges encountered have included difficulty in having VNA accept patients for short-term LAI visits, changes to where on the body the injection is delivered, and patients with SMI and their families being reluctant to depart from previous routines and administration schedules.

Continue to: There is great value...

There is great value in the collective lessons learned during this public health emergency (eg, the need for a flexible, population health-based approach; acceptability of combination telehealth and in-person visits) that can lead to more person-centered and accessible care for patients with SMI.

Acknowledgments

The authors thank North Suffolk Mental Health Association, the Freedom Trail Clinic, and their patients.

Bottom Line

When caring for a patient with a psychotic illness during the coronavirus disease 2019 (COVID-19) pandemic, evaluate whether it is necessary to continue a longacting injectable antipsychotic (LAI). If yes, reconsider which LAI should be administered, when and where it should be given, and by whom. Implement safety measures to minimize the risk of COVID-19 exposure and transmission.

Related Resources

• American Association of Community Psychiatrists. Clinical Tip Series. Long acting antipsychotic medications. https://drive.google.com/file/d/1unigjmjFJkqZMbaZ_ftdj8oqog49awZs/view?usp=sharing
• SMI Adviser. What are clinical considerations for giving LAIs during the COVID-19 public health emergency? https://smiadviser.org/knowledge_post/what-are-clinical-considerations-for-giving-lais-during-the-covid-19-public-health-emergency
• CDC. Infection control basics. https://www.cdc.gov/infectioncontrol/basics/index.html

Drug Brand Names

Aripiprazole • Abilify
Aripiprazole for extended- release injectable suspension • Abilify Maintena
Aripiprazole lauroxil • Aristada
Haloperidol • Haldol
Haloperidol injection • Haldol decanoate
Olanzapine • Zyprexa
Olanzapine for extended-release injectable suspension • Zyprexa Relprevv
Paliperidone • Invega
Paliperidone palmitate extended-release injectable suspension • Invega Sustenna
Paliperidone palmitate extended-release injectable suspension • Invega Trinza
Risperidone • Risperdal
Risperidone for extended- release injectable suspension • Perseris
Risperidone injection • Risperdal Consta

Long-acting injectable antipsychotics (LAIs) are an essential tool in the treatment of patients with psychotic disorders, allowing for periods of stable drug plasma concentration and confirmed adherence.¹ The current coronavirus disease 2019 (COVID-19) pandemic presents unique challenges for administering LAIs and requires a thoughtful and prospective approach in order to ensure continuity of psychiatric care while minimizing the risk of infection with COVID-19. Ideally, patients should be seen in person as infrequently as clinically prudent during this public health emergency; however, LAI administration necessitates direct physical contact between patient and clinician.

Patients with serious mental illness (SMI), who comprise the majority of individuals who receive LAIs, are at heightened risk for cardiovascular and pulmonary comorbidities. These factors are the primary reason the life expectancy of a patient with SMI is nearly 30 years shorter than that of the general population.^2-5 The risk of health care workers becoming infected or inadvertently spreading COVID-19 is heightened when working with patients in group living environments (ie, a shelter or group home), who have both increased exposure and increased risk of further transmission.⁶ Additional patient populations, including older adults, immunocompromised individuals, and those with preexisting conditions, are at heightened risk for serious complications if they were to contract COVID-19.^7,8

Thus, the questions of whether LAIs should be administered, and how to do so safely (both during the ongoing, acute phase of the pandemic as well as during the subsequent recovery period until the pandemic abates) need to be carefully considered. In this article, we provide concrete advice for clinicians and clinics on these topics, with the goal of maintaining patients’ psychiatric stability while protecting patients, health care workers, and the broader society from COVID-19 infection. Table 1 summarizes the questions regarding LAIs that clinicians need to address during this crisis. While we focus on outpatient care, inpatient teams should keep these considerations in mind if they are starting and discharging a patient on an LAI. More than ever, close collaboration and communication between inpatient and outpatient teams is critical.

Should an LAI be continued?

An important first step to approaching this challenge is to create a spreadsheet for all patients receiving LAIs. Focusing on a population-based approach is helpful to be systematic and ensure that no patients fall through the cracks during this public health emergency.⁹ Once all patients have been identified, the treatment team should review each patient to determine if continuing to administer the antipsychotic as an LAI formulation is essential, taking into account the patient’s current psychiatric status, historical medication adherence, potential severity and dangerousness of decompensation if nonadherent, and structures to support stability. For example, can a patient move in with family who can monitor medication adherence during the pandemic? Is it possible for the group home to assume medication administration? Additional consideration should be given to the living environment and health-vulnerability of the patient and the individuals living with them.

If the risk calculation does not point strongly towards a need for continuing the LAI, it may be prudent to temporarily transition the patient to the corresponding oral antipsychotic preparation. Table 2 lists all LAIs available in the United States and their approximate equivalent oral dosing. It is important to note that such transitions are not without clinical risk, to emphasize to the patient that the transition is intended as a temporary measure, and to discuss a proposed timeline for re-initiating the LAI. Also, emphasize to the patient and family that this transition does not diminish the previous reasoning for needing an LAI, but is a temporary measure taken in light of weighing the risks and benefits during a pandemic.

Which LAI should be administered?

If continuing the LAI is determined to be clinically necessary, consider switching the patient to a longer-acting preparation to maximize intervals between administrations and minimize the potential for infection. From a public health perspective, the longest clinically prudent interval between injections may be the most important consideration, provided the patient can receive a dose necessary to retain stability, and the LAI should be chosen accordingly. Deltoid injections may be able to be administered with reduced contact, or on a “drive-up” basis.¹⁰ Consider transitioning a patient who is receiving olanzapine pamoate to an alternate LAI or oral formulation, because the 3-hour observation period that is required after olanzapine pamoate administration is particularly problematic. While it may not be ideal to make medication changes during a pandemic, it is worth carefully weighing the patient’s stability and historical experience with other LAIs to determine if a safer/longer-spaced option is worth trying.¹¹

We recommend only switching among similar antipsychotics (ie, risperidone to paliperidone), or between different preparations of the same drug (ie, Abilify Maintena to Aristada), if possible, as these are the lowest risk transitions with regards to relapse. Table 3 provides examples.

Continue to: When should the LAI be administered?

The pharmacokinetics of LAIs allow for some flexibility in terms of when an LAI needs to be administered. The package inserts of all second-generation LAIs include missed-dose guidelines. These guidelines provide information on how long one can wait before the next injection is due, and what additional measures must be taken when beyond that date. Delaying an injection may be prudent, and the missed dose guidelines will indicate when one must consider supplementing with oral medications. For patients who are in quarantine, it may be better to delay an injection until the patient ends their quarantine than to deliver the dose during quarantine. Administering an injection earlier also is usually safe; off-cycle visits may help minimize patient contact (ie, if the patient happens to be coming into the vicinity of the clinic, or requires phlebotomy for therapeutic drug monitoring), and assist in planning for possible resurgences. When appropriate, and after considering the risk of worsening adverse effects, administering a higher dose than the usual maintenance dose would provide a buffer if the next injection was to be delayed. Therapeutic drug monitoring can help to optimize dosing and avoid low plasma drug levels, which may be not be sufficient, particularly during this time of stress.¹² To provide optimal protection against relapse, consider administering a dose that puts patients at the higher range of plasma drug levels.

Where can the LAI be administered, and who can give it?

For patients who usually travel to a clinic, consider arranging for a more local injection (ie, at the patient’s primary care clinic in their hometown, or at a local mental health center), and explore if the patient may be able to receive their injection in their home through a visiting nurse association (VNA). In many states (approximately 30 currently), clinicians at pharmacies are also able to administer patient injections. Clinics would do well to at least plan for alternate staffing models in the event of staff illness. A pool of individuals should be available to give injections; consider training additional staff members (including MDs who may have never previously administered an LAI but could be quickly instructed to do so) to administer LAIs. Theoretically, during a public health emergency, family members, particularly those who have a background in health care, could be trained to give an injection and provided education on LAI storage and post-injection monitoring. This approach would not be consistent with FDA labeling, however, and should only be considered as a last resort.

What safety measures can be put in place?

Face-to-face time for injection administration should be kept as brief as possible. Before the encounter, obtain the patient’s clinical information, ideally through telehealth or from an acceptable distance. Medication should be drawn ahead of time, and not in an enclosed space with the patient present. Strongly consider abandoning the traditional enclosed room for the injection, and instead use larger spaces, doorways, or outside, if feasible. As previously noted, some clinics and clinicians have used a drive-up approach for LAI administration, particularly for deltoid injections.¹⁰ Individuals who administer the injections should wear personal protective equipment, and the clinic should obtain an adequate supply of this equipment well in advance.

Lessons learned at our clinic

In our community mental health center clinic, planning around these questions has allowed us to provide safe and continuous psychiatric care with LAIs during this public health emergency while reducing the risk of infection. We have worked to transfer LAI administration to VNAs and transition patients to longer-lasting formulations or oral medications where appropriate, which has resulted in an approximately 50% decrease in in-person visits. Reducing the number of in-person visits does not need to result in less frequent clinical follow-up. Telepsychiatry visits can make up for lost in-person visits and have generally been well accepted.

As we are preparing for the next phase, routine medical health monitoring (eg, metabolic monitoring, monitoring for tardive dyskinesia) that has not been at the forefront of concerns should be carefully reintroduced. Challenges encountered have included difficulty in having VNA accept patients for short-term LAI visits, changes to where on the body the injection is delivered, and patients with SMI and their families being reluctant to depart from previous routines and administration schedules.

Continue to: There is great value...

There is great value in the collective lessons learned during this public health emergency (eg, the need for a flexible, population health-based approach; acceptability of combination telehealth and in-person visits) that can lead to more person-centered and accessible care for patients with SMI.

Acknowledgments

The authors thank North Suffolk Mental Health Association, the Freedom Trail Clinic, and their patients.

Bottom Line

When caring for a patient with a psychotic illness during the coronavirus disease 2019 (COVID-19) pandemic, evaluate whether it is necessary to continue a longacting injectable antipsychotic (LAI). If yes, reconsider which LAI should be administered, when and where it should be given, and by whom. Implement safety measures to minimize the risk of COVID-19 exposure and transmission.

Related Resources

• American Association of Community Psychiatrists. Clinical Tip Series. Long acting antipsychotic medications. https://drive.google.com/file/d/1unigjmjFJkqZMbaZ_ftdj8oqog49awZs/view?usp=sharing
• SMI Adviser. What are clinical considerations for giving LAIs during the COVID-19 public health emergency? https://smiadviser.org/knowledge_post/what-are-clinical-considerations-for-giving-lais-during-the-covid-19-public-health-emergency
• CDC. Infection control basics. https://www.cdc.gov/infectioncontrol/basics/index.html

Drug Brand Names

Aripiprazole • Abilify
Aripiprazole for extended- release injectable suspension • Abilify Maintena
Aripiprazole lauroxil • Aristada
Haloperidol • Haldol
Haloperidol injection • Haldol decanoate
Olanzapine • Zyprexa
Olanzapine for extended-release injectable suspension • Zyprexa Relprevv
Paliperidone • Invega
Paliperidone palmitate extended-release injectable suspension • Invega Sustenna
Paliperidone palmitate extended-release injectable suspension • Invega Trinza
Risperidone • Risperdal
Risperidone for extended- release injectable suspension • Perseris
Risperidone injection • Risperdal Consta

Long-acting injectable antipsychotics (LAIs) are an essential tool in the treatment of patients with psychotic disorders, allowing for periods of stable drug plasma concentration and confirmed adherence.¹ The current coronavirus disease 2019 (COVID-19) pandemic presents unique challenges for administering LAIs and requires a thoughtful and prospective approach in order to ensure continuity of psychiatric care while minimizing the risk of infection with COVID-19. Ideally, patients should be seen in person as infrequently as clinically prudent during this public health emergency; however, LAI administration necessitates direct physical contact between patient and clinician.

Patients with serious mental illness (SMI), who comprise the majority of individuals who receive LAIs, are at heightened risk for cardiovascular and pulmonary comorbidities. These factors are the primary reason the life expectancy of a patient with SMI is nearly 30 years shorter than that of the general population.^2-5 The risk of health care workers becoming infected or inadvertently spreading COVID-19 is heightened when working with patients in group living environments (ie, a shelter or group home), who have both increased exposure and increased risk of further transmission.⁶ Additional patient populations, including older adults, immunocompromised individuals, and those with preexisting conditions, are at heightened risk for serious complications if they were to contract COVID-19.^7,8

Thus, the questions of whether LAIs should be administered, and how to do so safely (both during the ongoing, acute phase of the pandemic as well as during the subsequent recovery period until the pandemic abates) need to be carefully considered. In this article, we provide concrete advice for clinicians and clinics on these topics, with the goal of maintaining patients’ psychiatric stability while protecting patients, health care workers, and the broader society from COVID-19 infection. Table 1 summarizes the questions regarding LAIs that clinicians need to address during this crisis. While we focus on outpatient care, inpatient teams should keep these considerations in mind if they are starting and discharging a patient on an LAI. More than ever, close collaboration and communication between inpatient and outpatient teams is critical.

Should an LAI be continued?

An important first step to approaching this challenge is to create a spreadsheet for all patients receiving LAIs. Focusing on a population-based approach is helpful to be systematic and ensure that no patients fall through the cracks during this public health emergency.⁹ Once all patients have been identified, the treatment team should review each patient to determine if continuing to administer the antipsychotic as an LAI formulation is essential, taking into account the patient’s current psychiatric status, historical medication adherence, potential severity and dangerousness of decompensation if nonadherent, and structures to support stability. For example, can a patient move in with family who can monitor medication adherence during the pandemic? Is it possible for the group home to assume medication administration? Additional consideration should be given to the living environment and health-vulnerability of the patient and the individuals living with them.

If the risk calculation does not point strongly towards a need for continuing the LAI, it may be prudent to temporarily transition the patient to the corresponding oral antipsychotic preparation. Table 2 lists all LAIs available in the United States and their approximate equivalent oral dosing. It is important to note that such transitions are not without clinical risk, to emphasize to the patient that the transition is intended as a temporary measure, and to discuss a proposed timeline for re-initiating the LAI. Also, emphasize to the patient and family that this transition does not diminish the previous reasoning for needing an LAI, but is a temporary measure taken in light of weighing the risks and benefits during a pandemic.

Which LAI should be administered?

If continuing the LAI is determined to be clinically necessary, consider switching the patient to a longer-acting preparation to maximize intervals between administrations and minimize the potential for infection. From a public health perspective, the longest clinically prudent interval between injections may be the most important consideration, provided the patient can receive a dose necessary to retain stability, and the LAI should be chosen accordingly. Deltoid injections may be able to be administered with reduced contact, or on a “drive-up” basis.¹⁰ Consider transitioning a patient who is receiving olanzapine pamoate to an alternate LAI or oral formulation, because the 3-hour observation period that is required after olanzapine pamoate administration is particularly problematic. While it may not be ideal to make medication changes during a pandemic, it is worth carefully weighing the patient’s stability and historical experience with other LAIs to determine if a safer/longer-spaced option is worth trying.¹¹

We recommend only switching among similar antipsychotics (ie, risperidone to paliperidone), or between different preparations of the same drug (ie, Abilify Maintena to Aristada), if possible, as these are the lowest risk transitions with regards to relapse. Table 3 provides examples.

Continue to: When should the LAI be administered?

The pharmacokinetics of LAIs allow for some flexibility in terms of when an LAI needs to be administered. The package inserts of all second-generation LAIs include missed-dose guidelines. These guidelines provide information on how long one can wait before the next injection is due, and what additional measures must be taken when beyond that date. Delaying an injection may be prudent, and the missed dose guidelines will indicate when one must consider supplementing with oral medications. For patients who are in quarantine, it may be better to delay an injection until the patient ends their quarantine than to deliver the dose during quarantine. Administering an injection earlier also is usually safe; off-cycle visits may help minimize patient contact (ie, if the patient happens to be coming into the vicinity of the clinic, or requires phlebotomy for therapeutic drug monitoring), and assist in planning for possible resurgences. When appropriate, and after considering the risk of worsening adverse effects, administering a higher dose than the usual maintenance dose would provide a buffer if the next injection was to be delayed. Therapeutic drug monitoring can help to optimize dosing and avoid low plasma drug levels, which may be not be sufficient, particularly during this time of stress.¹² To provide optimal protection against relapse, consider administering a dose that puts patients at the higher range of plasma drug levels.

Where can the LAI be administered, and who can give it?

For patients who usually travel to a clinic, consider arranging for a more local injection (ie, at the patient’s primary care clinic in their hometown, or at a local mental health center), and explore if the patient may be able to receive their injection in their home through a visiting nurse association (VNA). In many states (approximately 30 currently), clinicians at pharmacies are also able to administer patient injections. Clinics would do well to at least plan for alternate staffing models in the event of staff illness. A pool of individuals should be available to give injections; consider training additional staff members (including MDs who may have never previously administered an LAI but could be quickly instructed to do so) to administer LAIs. Theoretically, during a public health emergency, family members, particularly those who have a background in health care, could be trained to give an injection and provided education on LAI storage and post-injection monitoring. This approach would not be consistent with FDA labeling, however, and should only be considered as a last resort.

What safety measures can be put in place?

Face-to-face time for injection administration should be kept as brief as possible. Before the encounter, obtain the patient’s clinical information, ideally through telehealth or from an acceptable distance. Medication should be drawn ahead of time, and not in an enclosed space with the patient present. Strongly consider abandoning the traditional enclosed room for the injection, and instead use larger spaces, doorways, or outside, if feasible. As previously noted, some clinics and clinicians have used a drive-up approach for LAI administration, particularly for deltoid injections.¹⁰ Individuals who administer the injections should wear personal protective equipment, and the clinic should obtain an adequate supply of this equipment well in advance.

Lessons learned at our clinic

In our community mental health center clinic, planning around these questions has allowed us to provide safe and continuous psychiatric care with LAIs during this public health emergency while reducing the risk of infection. We have worked to transfer LAI administration to VNAs and transition patients to longer-lasting formulations or oral medications where appropriate, which has resulted in an approximately 50% decrease in in-person visits. Reducing the number of in-person visits does not need to result in less frequent clinical follow-up. Telepsychiatry visits can make up for lost in-person visits and have generally been well accepted.

As we are preparing for the next phase, routine medical health monitoring (eg, metabolic monitoring, monitoring for tardive dyskinesia) that has not been at the forefront of concerns should be carefully reintroduced. Challenges encountered have included difficulty in having VNA accept patients for short-term LAI visits, changes to where on the body the injection is delivered, and patients with SMI and their families being reluctant to depart from previous routines and administration schedules.

Continue to: There is great value...

There is great value in the collective lessons learned during this public health emergency (eg, the need for a flexible, population health-based approach; acceptability of combination telehealth and in-person visits) that can lead to more person-centered and accessible care for patients with SMI.

Acknowledgments

The authors thank North Suffolk Mental Health Association, the Freedom Trail Clinic, and their patients.

Bottom Line

When caring for a patient with a psychotic illness during the coronavirus disease 2019 (COVID-19) pandemic, evaluate whether it is necessary to continue a longacting injectable antipsychotic (LAI). If yes, reconsider which LAI should be administered, when and where it should be given, and by whom. Implement safety measures to minimize the risk of COVID-19 exposure and transmission.

Related Resources

• American Association of Community Psychiatrists. Clinical Tip Series. Long acting antipsychotic medications. https://drive.google.com/file/d/1unigjmjFJkqZMbaZ_ftdj8oqog49awZs/view?usp=sharing
• SMI Adviser. What are clinical considerations for giving LAIs during the COVID-19 public health emergency? https://smiadviser.org/knowledge_post/what-are-clinical-considerations-for-giving-lais-during-the-covid-19-public-health-emergency
• CDC. Infection control basics. https://www.cdc.gov/infectioncontrol/basics/index.html

Drug Brand Names

Aripiprazole • Abilify
Aripiprazole for extended- release injectable suspension • Abilify Maintena
Aripiprazole lauroxil • Aristada
Haloperidol • Haldol
Haloperidol injection • Haldol decanoate
Olanzapine • Zyprexa
Olanzapine for extended-release injectable suspension • Zyprexa Relprevv
Paliperidone • Invega
Paliperidone palmitate extended-release injectable suspension • Invega Sustenna
Paliperidone palmitate extended-release injectable suspension • Invega Trinza
Risperidone • Risperdal
Risperidone for extended- release injectable suspension • Perseris
Risperidone injection • Risperdal Consta