People over age 60 who drink alcohol regularly are at an increased risk of early death, particularly from cancer or issues related to the heart and blood vessels.

That’s according to the findings of a new, large study that was published in JAMA Network Openand build upon numerous other recent studies concluding that any amount of alcohol consumption is linked to significant health risks. That’s a change from decades of public health messaging suggesting that moderate alcohol intake (one or two drinks per day) wasn’t dangerous. Recently, experts have uncovered flaws in how researchers came to those earlier conclusions.

In this latest study, researchers in Spain analyzed health data for more than 135,000 people, all of whom were at least 60 years old, lived in the United Kingdom, and provided their health information to the UK Biobank database. The average age of people at the start of the analysis period was 64.

The researchers compared 12 years of health outcomes for occasional drinkers with those who averaged drinking at least some alcohol on a daily basis. The greatest health risks were seen between occasional drinkers and those whom the researchers labeled “high risk.” Occasional drinkers had less than about two drinks per week. The high-risk group included men who averaged nearly three drinks per day or more, and women who averaged about a drink and a half per day or more. The analysis showed that, compared with occasional drinking, high-risk drinking was linked to a 33% increased risk of early death, a 39% increased risk of dying from cancer, and a 21% increased risk of dying from problems with the heart and blood vessels.

More moderate drinking habits were also linked to an increased risk of early death and dying from cancer, and even just averaging about one drink or less daily was associated with an 11% higher risk of dying from cancer. Low and moderate drinkers were most at risk if they also had health problems or experienced socioeconomic factors like living in less affluent neighborhoods.

The findings also suggested the potential that mostly drinking wine, or drinking mostly with meals, may be lower risk, but the researchers called for further study on those topics since “it may mostly reflect the effect of healthier lifestyles, slower alcohol absorption, or nonalcoholic components of beverages.”

A recent Gallup poll showed that overall, Americans’ attitudes toward the health impacts of alcohol are changing, with 65% of young adults (ages 18-34) saying that drinking can have negative health effects. But just 39% of adults age 55 or older agreed that drinking is bad for a person’s health. The gap in perspectives between younger and older adults about drinking is the largest on record, Gallup reported.

The study investigators reported no conflicts of interest.

A version of this article first appeared on WebMD.com.

People over age 60 who drink alcohol regularly are at an increased risk of early death, particularly from cancer or issues related to the heart and blood vessels.

That’s according to the findings of a new, large study that was published in JAMA Network Openand build upon numerous other recent studies concluding that any amount of alcohol consumption is linked to significant health risks. That’s a change from decades of public health messaging suggesting that moderate alcohol intake (one or two drinks per day) wasn’t dangerous. Recently, experts have uncovered flaws in how researchers came to those earlier conclusions.

In this latest study, researchers in Spain analyzed health data for more than 135,000 people, all of whom were at least 60 years old, lived in the United Kingdom, and provided their health information to the UK Biobank database. The average age of people at the start of the analysis period was 64.

The researchers compared 12 years of health outcomes for occasional drinkers with those who averaged drinking at least some alcohol on a daily basis. The greatest health risks were seen between occasional drinkers and those whom the researchers labeled “high risk.” Occasional drinkers had less than about two drinks per week. The high-risk group included men who averaged nearly three drinks per day or more, and women who averaged about a drink and a half per day or more. The analysis showed that, compared with occasional drinking, high-risk drinking was linked to a 33% increased risk of early death, a 39% increased risk of dying from cancer, and a 21% increased risk of dying from problems with the heart and blood vessels.

More moderate drinking habits were also linked to an increased risk of early death and dying from cancer, and even just averaging about one drink or less daily was associated with an 11% higher risk of dying from cancer. Low and moderate drinkers were most at risk if they also had health problems or experienced socioeconomic factors like living in less affluent neighborhoods.

The findings also suggested the potential that mostly drinking wine, or drinking mostly with meals, may be lower risk, but the researchers called for further study on those topics since “it may mostly reflect the effect of healthier lifestyles, slower alcohol absorption, or nonalcoholic components of beverages.”

A recent Gallup poll showed that overall, Americans’ attitudes toward the health impacts of alcohol are changing, with 65% of young adults (ages 18-34) saying that drinking can have negative health effects. But just 39% of adults age 55 or older agreed that drinking is bad for a person’s health. The gap in perspectives between younger and older adults about drinking is the largest on record, Gallup reported.

The study investigators reported no conflicts of interest.

A version of this article first appeared on WebMD.com.

People over age 60 who drink alcohol regularly are at an increased risk of early death, particularly from cancer or issues related to the heart and blood vessels.

That’s according to the findings of a new, large study that was published in JAMA Network Openand build upon numerous other recent studies concluding that any amount of alcohol consumption is linked to significant health risks. That’s a change from decades of public health messaging suggesting that moderate alcohol intake (one or two drinks per day) wasn’t dangerous. Recently, experts have uncovered flaws in how researchers came to those earlier conclusions.

In this latest study, researchers in Spain analyzed health data for more than 135,000 people, all of whom were at least 60 years old, lived in the United Kingdom, and provided their health information to the UK Biobank database. The average age of people at the start of the analysis period was 64.

The researchers compared 12 years of health outcomes for occasional drinkers with those who averaged drinking at least some alcohol on a daily basis. The greatest health risks were seen between occasional drinkers and those whom the researchers labeled “high risk.” Occasional drinkers had less than about two drinks per week. The high-risk group included men who averaged nearly three drinks per day or more, and women who averaged about a drink and a half per day or more. The analysis showed that, compared with occasional drinking, high-risk drinking was linked to a 33% increased risk of early death, a 39% increased risk of dying from cancer, and a 21% increased risk of dying from problems with the heart and blood vessels.

More moderate drinking habits were also linked to an increased risk of early death and dying from cancer, and even just averaging about one drink or less daily was associated with an 11% higher risk of dying from cancer. Low and moderate drinkers were most at risk if they also had health problems or experienced socioeconomic factors like living in less affluent neighborhoods.

The findings also suggested the potential that mostly drinking wine, or drinking mostly with meals, may be lower risk, but the researchers called for further study on those topics since “it may mostly reflect the effect of healthier lifestyles, slower alcohol absorption, or nonalcoholic components of beverages.”

A recent Gallup poll showed that overall, Americans’ attitudes toward the health impacts of alcohol are changing, with 65% of young adults (ages 18-34) saying that drinking can have negative health effects. But just 39% of adults age 55 or older agreed that drinking is bad for a person’s health. The gap in perspectives between younger and older adults about drinking is the largest on record, Gallup reported.

The study investigators reported no conflicts of interest.

A version of this article first appeared on WebMD.com.

Key clinical point: Patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), and certain other autoimmune diseases (AID) may have an increased risk of developing psoriatic arthritis (PsA).

Major finding: The risk factors for PsA included RA (inverse variance weighting odds ratio [OR_IVW] 1.11; P = .0205), SLE (OR_IVW 1.04; P = .0107), AS (OR_IVW 2.18; P = .000155), Crohn's disease (CD; OR_IVW 1.07; P = .01), Hashimoto's thyroiditis (HT; OR_IVW 1.23; P = .00143), and vitiligo (OR_IVW 1.27; P = .0000267). However, PsA did not increase the risk for these AID.

Study details: This bidirectional two-sample Mendelian randomization study used genome-wide association data for PsA (3186 cases and 240,862 control individuals and  an additional 5065 cases and 21,286 control individuals), psoriasis, and AID.

Disclosures: This study was supported by two research projects from China. The authors declared no conflicts of interest.

Source: Duan K, Wang J, Chen S, et al. Causal associations between both psoriasis and psoriatic arthritis and multiple autoimmune diseases: A bidirectional two-sample Mendelian randomization study. Front. Immunol. 2024;15:1422626 (Jul 24). Doi: 10.3389/fimmu.2024.1422626 Source

Key clinical point: Patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), and certain other autoimmune diseases (AID) may have an increased risk of developing psoriatic arthritis (PsA).

Major finding: The risk factors for PsA included RA (inverse variance weighting odds ratio [OR_IVW] 1.11; P = .0205), SLE (OR_IVW 1.04; P = .0107), AS (OR_IVW 2.18; P = .000155), Crohn's disease (CD; OR_IVW 1.07; P = .01), Hashimoto's thyroiditis (HT; OR_IVW 1.23; P = .00143), and vitiligo (OR_IVW 1.27; P = .0000267). However, PsA did not increase the risk for these AID.

Study details: This bidirectional two-sample Mendelian randomization study used genome-wide association data for PsA (3186 cases and 240,862 control individuals and  an additional 5065 cases and 21,286 control individuals), psoriasis, and AID.

Disclosures: This study was supported by two research projects from China. The authors declared no conflicts of interest.

Source: Duan K, Wang J, Chen S, et al. Causal associations between both psoriasis and psoriatic arthritis and multiple autoimmune diseases: A bidirectional two-sample Mendelian randomization study. Front. Immunol. 2024;15:1422626 (Jul 24). Doi: 10.3389/fimmu.2024.1422626 Source

Key clinical point: Patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), and certain other autoimmune diseases (AID) may have an increased risk of developing psoriatic arthritis (PsA).

Major finding: The risk factors for PsA included RA (inverse variance weighting odds ratio [OR_IVW] 1.11; P = .0205), SLE (OR_IVW 1.04; P = .0107), AS (OR_IVW 2.18; P = .000155), Crohn's disease (CD; OR_IVW 1.07; P = .01), Hashimoto's thyroiditis (HT; OR_IVW 1.23; P = .00143), and vitiligo (OR_IVW 1.27; P = .0000267). However, PsA did not increase the risk for these AID.

Study details: This bidirectional two-sample Mendelian randomization study used genome-wide association data for PsA (3186 cases and 240,862 control individuals and  an additional 5065 cases and 21,286 control individuals), psoriasis, and AID.

Disclosures: This study was supported by two research projects from China. The authors declared no conflicts of interest.

Source: Duan K, Wang J, Chen S, et al. Causal associations between both psoriasis and psoriatic arthritis and multiple autoimmune diseases: A bidirectional two-sample Mendelian randomization study. Front. Immunol. 2024;15:1422626 (Jul 24). Doi: 10.3389/fimmu.2024.1422626 Source

Key clinical point: The second proximal interphalangeal (PIP) joint of the right hand and the right knee joint were the most affected in patients with psoriatic arthritis (PsA), particularly in those with older age and an earlier onset of PsA.

Major finding: The second PIP joint of the right hand had the greatest prevalence of swelling (18.9%), and the right knee joint had the highest prevalence of tenderness (24.2%). Older age was a risk factor, whereas an earlier onset of PsA was a protective factor for both swelling of the second PIP joint of the right hand and tenderness of right knee joint (P < .05 for all).

Study details: This cross-sectional study included 264 patients with PsA.

Disclosures: This study was funded by the National Key Research and Development Program of China and the National Natural Science Foundation of China. The authors did not declare any conflicts of interest.

Source: Li J, Xiao J, Xie X, et al. Individual joints involvement pattern in psoriatic arthritis: A cross-sectional study in China. J Dermatol. 2024 (Jul 12). Doi: 10.1111/1346-8138.17369 Source

Key clinical point: The second proximal interphalangeal (PIP) joint of the right hand and the right knee joint were the most affected in patients with psoriatic arthritis (PsA), particularly in those with older age and an earlier onset of PsA.

Major finding: The second PIP joint of the right hand had the greatest prevalence of swelling (18.9%), and the right knee joint had the highest prevalence of tenderness (24.2%). Older age was a risk factor, whereas an earlier onset of PsA was a protective factor for both swelling of the second PIP joint of the right hand and tenderness of right knee joint (P < .05 for all).

Study details: This cross-sectional study included 264 patients with PsA.

Disclosures: This study was funded by the National Key Research and Development Program of China and the National Natural Science Foundation of China. The authors did not declare any conflicts of interest.

Source: Li J, Xiao J, Xie X, et al. Individual joints involvement pattern in psoriatic arthritis: A cross-sectional study in China. J Dermatol. 2024 (Jul 12). Doi: 10.1111/1346-8138.17369 Source

Key clinical point: The second proximal interphalangeal (PIP) joint of the right hand and the right knee joint were the most affected in patients with psoriatic arthritis (PsA), particularly in those with older age and an earlier onset of PsA.

Major finding: The second PIP joint of the right hand had the greatest prevalence of swelling (18.9%), and the right knee joint had the highest prevalence of tenderness (24.2%). Older age was a risk factor, whereas an earlier onset of PsA was a protective factor for both swelling of the second PIP joint of the right hand and tenderness of right knee joint (P < .05 for all).

Study details: This cross-sectional study included 264 patients with PsA.

Disclosures: This study was funded by the National Key Research and Development Program of China and the National Natural Science Foundation of China. The authors did not declare any conflicts of interest.

Source: Li J, Xiao J, Xie X, et al. Individual joints involvement pattern in psoriatic arthritis: A cross-sectional study in China. J Dermatol. 2024 (Jul 12). Doi: 10.1111/1346-8138.17369 Source

Key clinical point: A dose of 160 mg bimekizumab every 4 weeks demonstrated greater long-term efficacy than 45 or 90 mg ustekinumab every 12 weeks in patients with psoriatic arthritis (PsA) who were biologic-naïve or showed inadequate response to tumor necrosis factor inhibitors (TNFi-IR).

Major finding: At week 52, both biologic-naive (adjusted odds ratio [aOR] 3.33; P < .001) and TNFi-IR (aOR 9.85; P < .001) patients receiving bimekizumab vs 45 mg ustekinumab were more likely to achieve ≥70% improvement in the American College of Rheumatology response, with similar effect observed for bimekizumab vs 90 mg ustekinumab.

Study details: This was matching-adjusted indirect comparison of data from several phase 3 trials of bimekizumab (BE OPTIMAL, BE COMPLETE, and BE VITAL) and ustekinumab (PSUMMIT1 and PSUMMIT2). The trials involved patients with PsA who received bimekizumab (n = 698) or ustekinumab (45 mg: n = 265; 90 mg: n = 262).

Disclosures: This study was sponsored by UCB Pharma and supported by the NIHR Manchester Biomedical Research Centre, UK. Three authors declared being employees and shareholders of UCB Pharma. Several authors declared having ties with various sources, including UCB Pharma.

Source: Mease PJ, Warren RB, Nash P, et al. Comparative effectiveness of bimekizumab and ustekinumab in patients with psoriatic arthritis at 52 weeks assessed using a matching-adjusted indirect comparison. Rheumatol Ther. 2024 (Aug 9). Doi: 10.1007/s40744-024-00705-x Source

Key clinical point: A dose of 160 mg bimekizumab every 4 weeks demonstrated greater long-term efficacy than 45 or 90 mg ustekinumab every 12 weeks in patients with psoriatic arthritis (PsA) who were biologic-naïve or showed inadequate response to tumor necrosis factor inhibitors (TNFi-IR).

Major finding: At week 52, both biologic-naive (adjusted odds ratio [aOR] 3.33; P < .001) and TNFi-IR (aOR 9.85; P < .001) patients receiving bimekizumab vs 45 mg ustekinumab were more likely to achieve ≥70% improvement in the American College of Rheumatology response, with similar effect observed for bimekizumab vs 90 mg ustekinumab.

Study details: This was matching-adjusted indirect comparison of data from several phase 3 trials of bimekizumab (BE OPTIMAL, BE COMPLETE, and BE VITAL) and ustekinumab (PSUMMIT1 and PSUMMIT2). The trials involved patients with PsA who received bimekizumab (n = 698) or ustekinumab (45 mg: n = 265; 90 mg: n = 262).

Disclosures: This study was sponsored by UCB Pharma and supported by the NIHR Manchester Biomedical Research Centre, UK. Three authors declared being employees and shareholders of UCB Pharma. Several authors declared having ties with various sources, including UCB Pharma.

Source: Mease PJ, Warren RB, Nash P, et al. Comparative effectiveness of bimekizumab and ustekinumab in patients with psoriatic arthritis at 52 weeks assessed using a matching-adjusted indirect comparison. Rheumatol Ther. 2024 (Aug 9). Doi: 10.1007/s40744-024-00705-x Source

Key clinical point: A dose of 160 mg bimekizumab every 4 weeks demonstrated greater long-term efficacy than 45 or 90 mg ustekinumab every 12 weeks in patients with psoriatic arthritis (PsA) who were biologic-naïve or showed inadequate response to tumor necrosis factor inhibitors (TNFi-IR).

Major finding: At week 52, both biologic-naive (adjusted odds ratio [aOR] 3.33; P < .001) and TNFi-IR (aOR 9.85; P < .001) patients receiving bimekizumab vs 45 mg ustekinumab were more likely to achieve ≥70% improvement in the American College of Rheumatology response, with similar effect observed for bimekizumab vs 90 mg ustekinumab.

Study details: This was matching-adjusted indirect comparison of data from several phase 3 trials of bimekizumab (BE OPTIMAL, BE COMPLETE, and BE VITAL) and ustekinumab (PSUMMIT1 and PSUMMIT2). The trials involved patients with PsA who received bimekizumab (n = 698) or ustekinumab (45 mg: n = 265; 90 mg: n = 262).

Disclosures: This study was sponsored by UCB Pharma and supported by the NIHR Manchester Biomedical Research Centre, UK. Three authors declared being employees and shareholders of UCB Pharma. Several authors declared having ties with various sources, including UCB Pharma.

Source: Mease PJ, Warren RB, Nash P, et al. Comparative effectiveness of bimekizumab and ustekinumab in patients with psoriatic arthritis at 52 weeks assessed using a matching-adjusted indirect comparison. Rheumatol Ther. 2024 (Aug 9). Doi: 10.1007/s40744-024-00705-x Source

Key clinical point: First-line targeted therapy, particularly use of tumor necrosis factor inhibitors (TNFi), reduced the use of symptomatic treatments, methotrexate, mood disorder treatments, hospitalizations, and sick leave in patients with psoriatic arthritis (PsA).

Major finding: First-line targeted therapy significantly reduced the use of non-steroidal anti-inflammatory drugs (NSAID; −15%), prednisone (−9%), methotrexate (−15%), mood disorder treatments (−2%), and rate of hospitalizations (−12%) and sick leave (−4%; all P < 10^-4). TNFi showed greater reductions in NSAID (adjusted odds ratio [aOR] 1.04; 95% CI 1.01-1.07) and prednisone use (aOR 1.04; 95% CI 1.02-1.06) compared with interleukin 17 inhibitors (IL17i), with similar outcomes for IL12/23i.

Study details: This cohort study included 9793 patients with PsA age ≥18 years who had initiated targeted therapies for at least 9 months.

Disclosures: The authors did not declare any specific funding. Two authors declared receiving a subsidy to attend a congress or receiving consulting fees and serving as investigators for various sources.

Source: Pina Vegas L, Iggui S, Sbidian E, Claudepierre P. Impact of initiation of targeted therapy on the use of psoriatic arthritis-related treatments and healthcare consumption: A cohort study of 9793 patients from the French health insurance database (SNDS). RMD Open. 2024;10:e004631 (Aug 7). Doi: 10.1136/rmdopen-2024-004631 Source

Key clinical point: First-line targeted therapy, particularly use of tumor necrosis factor inhibitors (TNFi), reduced the use of symptomatic treatments, methotrexate, mood disorder treatments, hospitalizations, and sick leave in patients with psoriatic arthritis (PsA).

Major finding: First-line targeted therapy significantly reduced the use of non-steroidal anti-inflammatory drugs (NSAID; −15%), prednisone (−9%), methotrexate (−15%), mood disorder treatments (−2%), and rate of hospitalizations (−12%) and sick leave (−4%; all P < 10^-4). TNFi showed greater reductions in NSAID (adjusted odds ratio [aOR] 1.04; 95% CI 1.01-1.07) and prednisone use (aOR 1.04; 95% CI 1.02-1.06) compared with interleukin 17 inhibitors (IL17i), with similar outcomes for IL12/23i.

Study details: This cohort study included 9793 patients with PsA age ≥18 years who had initiated targeted therapies for at least 9 months.

Disclosures: The authors did not declare any specific funding. Two authors declared receiving a subsidy to attend a congress or receiving consulting fees and serving as investigators for various sources.

Source: Pina Vegas L, Iggui S, Sbidian E, Claudepierre P. Impact of initiation of targeted therapy on the use of psoriatic arthritis-related treatments and healthcare consumption: A cohort study of 9793 patients from the French health insurance database (SNDS). RMD Open. 2024;10:e004631 (Aug 7). Doi: 10.1136/rmdopen-2024-004631 Source

Key clinical point: First-line targeted therapy, particularly use of tumor necrosis factor inhibitors (TNFi), reduced the use of symptomatic treatments, methotrexate, mood disorder treatments, hospitalizations, and sick leave in patients with psoriatic arthritis (PsA).

Major finding: First-line targeted therapy significantly reduced the use of non-steroidal anti-inflammatory drugs (NSAID; −15%), prednisone (−9%), methotrexate (−15%), mood disorder treatments (−2%), and rate of hospitalizations (−12%) and sick leave (−4%; all P < 10^-4). TNFi showed greater reductions in NSAID (adjusted odds ratio [aOR] 1.04; 95% CI 1.01-1.07) and prednisone use (aOR 1.04; 95% CI 1.02-1.06) compared with interleukin 17 inhibitors (IL17i), with similar outcomes for IL12/23i.

Study details: This cohort study included 9793 patients with PsA age ≥18 years who had initiated targeted therapies for at least 9 months.

Disclosures: The authors did not declare any specific funding. Two authors declared receiving a subsidy to attend a congress or receiving consulting fees and serving as investigators for various sources.

Source: Pina Vegas L, Iggui S, Sbidian E, Claudepierre P. Impact of initiation of targeted therapy on the use of psoriatic arthritis-related treatments and healthcare consumption: A cohort study of 9793 patients from the French health insurance database (SNDS). RMD Open. 2024;10:e004631 (Aug 7). Doi: 10.1136/rmdopen-2024-004631 Source

Key clinical point: Patients with psoriatic arthritis (PsA) who achieved disease control despite having an inadequate response to conventional synthetic or biological disease-modifying antirheumatic drugs (cs/bDMARD) showed improved patient-reported outcomes (PRO).

Major finding: At week 104, patients who did vs did not achieve minimal disease activity had significant improvements in the Health Assessment Questionnaire–Disability Index (least squares mean change from baseline [Δ] −0.82 vs −0.17; P ≤ .0001), pain (Δ −4.75 vs −1.77; P ≤ .0001), and other investigated PRO.

Study details: This post hoc analysis of two phase 3 trials, SELECT-PsA 1 and SELECT-PsA 2, included 1069 and 317 patients with PsA and inadequate response to ≥1 csDMARD or bDMARD, respectively, who were randomly assigned to receive upadacitinib, placebo with crossover to upadacitinib, or adalimumab.

Disclosures: This study was funded by AbbVie, and AbbVie participated in the design of the trial and the publication of its results. Seven authors declared being employees of AbbVie and may own its stock or stock options. Several authors declared having ties with AbbVie and other sources.

Source: Kavanaugh A, Mease P, Gossec L, et al. Association between achievement of clinical disease control and improvement in patient-reported outcomes and quality of life in patients with psoriatic arthritis in the phase 3 SELECT-PsA 1 and 2 randomized controlled trials. ACR Open Rheumatol. 2024 (Aug 1). Doi: 10.1002/acr2.11714 Source

Key clinical point: Patients with psoriatic arthritis (PsA) who achieved disease control despite having an inadequate response to conventional synthetic or biological disease-modifying antirheumatic drugs (cs/bDMARD) showed improved patient-reported outcomes (PRO).

Major finding: At week 104, patients who did vs did not achieve minimal disease activity had significant improvements in the Health Assessment Questionnaire–Disability Index (least squares mean change from baseline [Δ] −0.82 vs −0.17; P ≤ .0001), pain (Δ −4.75 vs −1.77; P ≤ .0001), and other investigated PRO.

Study details: This post hoc analysis of two phase 3 trials, SELECT-PsA 1 and SELECT-PsA 2, included 1069 and 317 patients with PsA and inadequate response to ≥1 csDMARD or bDMARD, respectively, who were randomly assigned to receive upadacitinib, placebo with crossover to upadacitinib, or adalimumab.

Disclosures: This study was funded by AbbVie, and AbbVie participated in the design of the trial and the publication of its results. Seven authors declared being employees of AbbVie and may own its stock or stock options. Several authors declared having ties with AbbVie and other sources.

Source: Kavanaugh A, Mease P, Gossec L, et al. Association between achievement of clinical disease control and improvement in patient-reported outcomes and quality of life in patients with psoriatic arthritis in the phase 3 SELECT-PsA 1 and 2 randomized controlled trials. ACR Open Rheumatol. 2024 (Aug 1). Doi: 10.1002/acr2.11714 Source

Key clinical point: Patients with psoriatic arthritis (PsA) who achieved disease control despite having an inadequate response to conventional synthetic or biological disease-modifying antirheumatic drugs (cs/bDMARD) showed improved patient-reported outcomes (PRO).

Major finding: At week 104, patients who did vs did not achieve minimal disease activity had significant improvements in the Health Assessment Questionnaire–Disability Index (least squares mean change from baseline [Δ] −0.82 vs −0.17; P ≤ .0001), pain (Δ −4.75 vs −1.77; P ≤ .0001), and other investigated PRO.

Study details: This post hoc analysis of two phase 3 trials, SELECT-PsA 1 and SELECT-PsA 2, included 1069 and 317 patients with PsA and inadequate response to ≥1 csDMARD or bDMARD, respectively, who were randomly assigned to receive upadacitinib, placebo with crossover to upadacitinib, or adalimumab.

Disclosures: This study was funded by AbbVie, and AbbVie participated in the design of the trial and the publication of its results. Seven authors declared being employees of AbbVie and may own its stock or stock options. Several authors declared having ties with AbbVie and other sources.

Source: Kavanaugh A, Mease P, Gossec L, et al. Association between achievement of clinical disease control and improvement in patient-reported outcomes and quality of life in patients with psoriatic arthritis in the phase 3 SELECT-PsA 1 and 2 randomized controlled trials. ACR Open Rheumatol. 2024 (Aug 1). Doi: 10.1002/acr2.11714 Source

Key clinical point: Patients who received interleukin-23 inhibitors (IL-23i) and interleukin-12/23 inhibitors (IL-12/23i) for the management of psoriasis had a comparable risk for incident psoriatic arthritis (PsA).

Major finding: Patients treated with IL-23i vs IL-12/23i demonstrated no significant difference in the risk for PsA (hazard ratio 0.96; P = .812) and cumulative incidence of PsA (P = .812).

Study details: This retrospective cohort study included the propensity score–matched data of patients with psoriasis age 18 years or older from the TriNetX database who were treated with either IL-23i (n = 2142) or IL-12/23i (n = 2142).

Disclosures: This study did not receive any specific funding. The authors declared no conflicts of interest.

Source: Tsai SHL, Yang C-Y, Huo A-P, Wei JC-C. Interleukin 23 versus interleukin 12/23 inhibitors on preventing incidental psoriatic arthritis in patients with psoriasis? A real-world comparison from the TriNetX Global Collaborative Network. J Am Acad Dermatol. 2024 (Jul 27). Doi: 0.1016/j.jaad.2024.07.1473 Source

Key clinical point: Patients who received interleukin-23 inhibitors (IL-23i) and interleukin-12/23 inhibitors (IL-12/23i) for the management of psoriasis had a comparable risk for incident psoriatic arthritis (PsA).

Major finding: Patients treated with IL-23i vs IL-12/23i demonstrated no significant difference in the risk for PsA (hazard ratio 0.96; P = .812) and cumulative incidence of PsA (P = .812).

Study details: This retrospective cohort study included the propensity score–matched data of patients with psoriasis age 18 years or older from the TriNetX database who were treated with either IL-23i (n = 2142) or IL-12/23i (n = 2142).

Disclosures: This study did not receive any specific funding. The authors declared no conflicts of interest.

Source: Tsai SHL, Yang C-Y, Huo A-P, Wei JC-C. Interleukin 23 versus interleukin 12/23 inhibitors on preventing incidental psoriatic arthritis in patients with psoriasis? A real-world comparison from the TriNetX Global Collaborative Network. J Am Acad Dermatol. 2024 (Jul 27). Doi: 0.1016/j.jaad.2024.07.1473 Source

Key clinical point: Patients who received interleukin-23 inhibitors (IL-23i) and interleukin-12/23 inhibitors (IL-12/23i) for the management of psoriasis had a comparable risk for incident psoriatic arthritis (PsA).

Major finding: Patients treated with IL-23i vs IL-12/23i demonstrated no significant difference in the risk for PsA (hazard ratio 0.96; P = .812) and cumulative incidence of PsA (P = .812).

Study details: This retrospective cohort study included the propensity score–matched data of patients with psoriasis age 18 years or older from the TriNetX database who were treated with either IL-23i (n = 2142) or IL-12/23i (n = 2142).

Disclosures: This study did not receive any specific funding. The authors declared no conflicts of interest.

Source: Tsai SHL, Yang C-Y, Huo A-P, Wei JC-C. Interleukin 23 versus interleukin 12/23 inhibitors on preventing incidental psoriatic arthritis in patients with psoriasis? A real-world comparison from the TriNetX Global Collaborative Network. J Am Acad Dermatol. 2024 (Jul 27). Doi: 0.1016/j.jaad.2024.07.1473 Source

Key clinical point: Bimekizumab demonstrated sustained efficacy and was well tolerated for 52 weeks, regardless of concomitant methotrexate use, in patients with psoriatic arthritis (PsA) who were biologic-naive or intolerant to tumor necrosis factor inhibitors (TNFi-IR).

Major finding: Through week 52, nearly half of the patients receiving bimekizumab with or without methotrexate achieved a ≥50% improvement in American College of Rheumatology response (biologic-naive ~55%; TNFi-IR ~48-56%) and minimal disease activity (biologic-naive ~55%; TNFi-IR ~47%). The rates of experiencing at least one treatment emergent adverse event were similar across the subgroups.

Study details: This post hoc analysis of phase 3 trials (BE OPTIMAL, BE COMPLETE, and BE VITAL) included biologic-naive (n = 852) or TNFi-IR (n = 400) patients with PsA who received bimekizumab, placebo with crossover to bimekizumab at week 16, or adalimumab, with or without methotrexate.

Disclosures: This study was funded by UCB Pharma and supported by the NIHR Manchester Biomedical Research Centre, UK. Two authors declared being employees of or holding stocks in UCB. Several authors declared having other ties with UCB and other sources.

Source: McInnes IB, Mease PJ, Tanaka Y, et al. Efficacy and safety of bimekizumab in patients with psoriatic arthritis with or without methotrexate: 52-week results from two phase 3 studies. ACR Open Rheumatol. 2024 (Jul 30). Doi: 10.1002/acr2.11727 Source

Key clinical point: Bimekizumab demonstrated sustained efficacy and was well tolerated for 52 weeks, regardless of concomitant methotrexate use, in patients with psoriatic arthritis (PsA) who were biologic-naive or intolerant to tumor necrosis factor inhibitors (TNFi-IR).

Major finding: Through week 52, nearly half of the patients receiving bimekizumab with or without methotrexate achieved a ≥50% improvement in American College of Rheumatology response (biologic-naive ~55%; TNFi-IR ~48-56%) and minimal disease activity (biologic-naive ~55%; TNFi-IR ~47%). The rates of experiencing at least one treatment emergent adverse event were similar across the subgroups.

Study details: This post hoc analysis of phase 3 trials (BE OPTIMAL, BE COMPLETE, and BE VITAL) included biologic-naive (n = 852) or TNFi-IR (n = 400) patients with PsA who received bimekizumab, placebo with crossover to bimekizumab at week 16, or adalimumab, with or without methotrexate.

Disclosures: This study was funded by UCB Pharma and supported by the NIHR Manchester Biomedical Research Centre, UK. Two authors declared being employees of or holding stocks in UCB. Several authors declared having other ties with UCB and other sources.

Source: McInnes IB, Mease PJ, Tanaka Y, et al. Efficacy and safety of bimekizumab in patients with psoriatic arthritis with or without methotrexate: 52-week results from two phase 3 studies. ACR Open Rheumatol. 2024 (Jul 30). Doi: 10.1002/acr2.11727 Source

Key clinical point: Bimekizumab demonstrated sustained efficacy and was well tolerated for 52 weeks, regardless of concomitant methotrexate use, in patients with psoriatic arthritis (PsA) who were biologic-naive or intolerant to tumor necrosis factor inhibitors (TNFi-IR).

Major finding: Through week 52, nearly half of the patients receiving bimekizumab with or without methotrexate achieved a ≥50% improvement in American College of Rheumatology response (biologic-naive ~55%; TNFi-IR ~48-56%) and minimal disease activity (biologic-naive ~55%; TNFi-IR ~47%). The rates of experiencing at least one treatment emergent adverse event were similar across the subgroups.

Study details: This post hoc analysis of phase 3 trials (BE OPTIMAL, BE COMPLETE, and BE VITAL) included biologic-naive (n = 852) or TNFi-IR (n = 400) patients with PsA who received bimekizumab, placebo with crossover to bimekizumab at week 16, or adalimumab, with or without methotrexate.

Disclosures: This study was funded by UCB Pharma and supported by the NIHR Manchester Biomedical Research Centre, UK. Two authors declared being employees of or holding stocks in UCB. Several authors declared having other ties with UCB and other sources.

Source: McInnes IB, Mease PJ, Tanaka Y, et al. Efficacy and safety of bimekizumab in patients with psoriatic arthritis with or without methotrexate: 52-week results from two phase 3 studies. ACR Open Rheumatol. 2024 (Jul 30). Doi: 10.1002/acr2.11727 Source

Given the clinical presentation and the absence of other systemic or dermatological findings, the diagnosis of chevron nails was made.

Discussion

Chevron nails, also known as V-shaped nails or herringbone nails, are an uncommon but benign nail condition typically observed in infancy and early childhood. The condition is characterized by transverse ridges on the nails that converge towards the center, forming a V or chevron shape. This condition was first described by Perry et al. and later by Shuster et al., who explained that the condition might result from axial growth of the nail with synchronous growth occurring from a chevron-shaped growing edge of the nail root. Alternatively, Shuster suggested that sequential growth, with localized variation in the nail production rate, could propagate a wave from the center of the nail to the edge.

The etiology of chevron nails is not well understood, but it is believed to result from temporary disruptions in the nail matrix, possibly related to minor illness or physiological stress during infancy.

In the case of our 7-month-old patient, the history of mild upper respiratory infections might have contributed to the development of chevron nails. However, the lack of other significant illness, skin involvement, or systemic findings supports the benign and self-limiting nature of this condition. Parents were reassured that chevron nails typically resolve on their own as the child grows and that no specific treatment is necessary.
 

Differential Diagnosis

The differential diagnosis of transverse nail changes in children includes other conditions such as trachyonychia, lichen planus, Darier disease, and pachyonychia congenita.

Trachyonychia, also known as “sandpaper nails,” trachyonychia is characterized by the roughening of the nail surface, giving it a dull and ridged appearance. The condition may affect all 20 nails and is often associated with underlying dermatological conditions such as lichen planus or alopecia areata. Unlike chevron nails, trachyonychia presents with more diffuse nail changes and does not typically feature the distinct V-shaped ridging seen in this patient.

Lichen planus is an inflammatory condition that can affect the skin, mucous membranes, and nails. Nail involvement in lichen planus can lead to longitudinal ridging, thinning, and sometimes even complete nail loss. The absence of other characteristic features of lichen planus, such as violaceous papules on the skin or white lacy patterns on mucous membranes (Wickham striae), makes this diagnosis less likely in our patient.

Darier disease, also known as keratosis follicularis, is a genetic disorder characterized by greasy, warty papules primarily on seborrheic areas of the skin, nail abnormalities, and sometimes mucosal involvement. Nail changes in Darier disease include longitudinal red and white streaks, V-shaped notching at the free edge of the nails, and subungual hyperkeratosis. These nail changes are more severe and distinct than the simple transverse ridging seen in chevron nails. The absence of other clinical signs of Darier disease, such as skin papules or characteristic nail notching, makes this diagnosis unlikely in our patient.

Pachyonychia congenita is a rare genetic disorder characterized by thickened nails (pachyonychia), painful plantar keratoderma, and sometimes oral leukokeratosis. The condition typically presents with significant nail thickening and other systemic findings, which were absent in our patient. The distinct pattern of V-shaped ridging observed in chevron nails does not align with the typical presentation of pachyonychia congenita.
 

Next Steps

No specific treatment is required for chevron nails. The condition is typically self-resolving, and the nails usually return to a normal appearance as the child continues to grow. Parents were advised to monitor the nails for any changes or new symptoms and were reassured about the benign nature of the findings. Follow-up was scheduled to ensure the resolution of the condition as the child develops.

Conclusion

Chevron nails are an important consideration in the differential diagnosis of transverse nail ridging in infants and young children. While the condition is benign and self-limiting, it is crucial to differentiate it from other nail dystrophies, such as trachyonychia, lichen planus, Darier disease, and pachyonychia congenita, which may require further investigation or intervention. Awareness of chevron nails can help prevent unnecessary worry and provide reassurance to parents and caregivers.
 

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.

Suggested Reading

Delano S, Belazarian L. Chevron nails: A normal variant in the pediatric population. Pediatr Dermatol. 2014 Jan-Feb;31(1):e24-5. doi: 10.1111/pde.12193.

John JM et al. Chevron nail — An under-recognised normal variant of nail development. Arch Dis Child. 2024 Jul 18;109(8):648. doi: 10.1136/archdischild-2024-326975.

Shuster S. The significance of chevron nails. Br J Dermatol. 1996;135:151–152. doi: 10.1046/j.1365-2133.1996.d01-961.x.

Starace M et al. Nail disorders in children. Skin Appendage Disord. 2018 Oct;4(4):217-229. doi: 10.1159/000486020.

Given the clinical presentation and the absence of other systemic or dermatological findings, the diagnosis of chevron nails was made.

Discussion

Chevron nails, also known as V-shaped nails or herringbone nails, are an uncommon but benign nail condition typically observed in infancy and early childhood. The condition is characterized by transverse ridges on the nails that converge towards the center, forming a V or chevron shape. This condition was first described by Perry et al. and later by Shuster et al., who explained that the condition might result from axial growth of the nail with synchronous growth occurring from a chevron-shaped growing edge of the nail root. Alternatively, Shuster suggested that sequential growth, with localized variation in the nail production rate, could propagate a wave from the center of the nail to the edge.

The etiology of chevron nails is not well understood, but it is believed to result from temporary disruptions in the nail matrix, possibly related to minor illness or physiological stress during infancy.

In the case of our 7-month-old patient, the history of mild upper respiratory infections might have contributed to the development of chevron nails. However, the lack of other significant illness, skin involvement, or systemic findings supports the benign and self-limiting nature of this condition. Parents were reassured that chevron nails typically resolve on their own as the child grows and that no specific treatment is necessary.
 

Differential Diagnosis

The differential diagnosis of transverse nail changes in children includes other conditions such as trachyonychia, lichen planus, Darier disease, and pachyonychia congenita.

Trachyonychia, also known as “sandpaper nails,” trachyonychia is characterized by the roughening of the nail surface, giving it a dull and ridged appearance. The condition may affect all 20 nails and is often associated with underlying dermatological conditions such as lichen planus or alopecia areata. Unlike chevron nails, trachyonychia presents with more diffuse nail changes and does not typically feature the distinct V-shaped ridging seen in this patient.

Lichen planus is an inflammatory condition that can affect the skin, mucous membranes, and nails. Nail involvement in lichen planus can lead to longitudinal ridging, thinning, and sometimes even complete nail loss. The absence of other characteristic features of lichen planus, such as violaceous papules on the skin or white lacy patterns on mucous membranes (Wickham striae), makes this diagnosis less likely in our patient.

Darier disease, also known as keratosis follicularis, is a genetic disorder characterized by greasy, warty papules primarily on seborrheic areas of the skin, nail abnormalities, and sometimes mucosal involvement. Nail changes in Darier disease include longitudinal red and white streaks, V-shaped notching at the free edge of the nails, and subungual hyperkeratosis. These nail changes are more severe and distinct than the simple transverse ridging seen in chevron nails. The absence of other clinical signs of Darier disease, such as skin papules or characteristic nail notching, makes this diagnosis unlikely in our patient.

Pachyonychia congenita is a rare genetic disorder characterized by thickened nails (pachyonychia), painful plantar keratoderma, and sometimes oral leukokeratosis. The condition typically presents with significant nail thickening and other systemic findings, which were absent in our patient. The distinct pattern of V-shaped ridging observed in chevron nails does not align with the typical presentation of pachyonychia congenita.
 

Next Steps

No specific treatment is required for chevron nails. The condition is typically self-resolving, and the nails usually return to a normal appearance as the child continues to grow. Parents were advised to monitor the nails for any changes or new symptoms and were reassured about the benign nature of the findings. Follow-up was scheduled to ensure the resolution of the condition as the child develops.

Conclusion

Chevron nails are an important consideration in the differential diagnosis of transverse nail ridging in infants and young children. While the condition is benign and self-limiting, it is crucial to differentiate it from other nail dystrophies, such as trachyonychia, lichen planus, Darier disease, and pachyonychia congenita, which may require further investigation or intervention. Awareness of chevron nails can help prevent unnecessary worry and provide reassurance to parents and caregivers.
 

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.

Suggested Reading

Delano S, Belazarian L. Chevron nails: A normal variant in the pediatric population. Pediatr Dermatol. 2014 Jan-Feb;31(1):e24-5. doi: 10.1111/pde.12193.

John JM et al. Chevron nail — An under-recognised normal variant of nail development. Arch Dis Child. 2024 Jul 18;109(8):648. doi: 10.1136/archdischild-2024-326975.

Shuster S. The significance of chevron nails. Br J Dermatol. 1996;135:151–152. doi: 10.1046/j.1365-2133.1996.d01-961.x.

Starace M et al. Nail disorders in children. Skin Appendage Disord. 2018 Oct;4(4):217-229. doi: 10.1159/000486020.

Given the clinical presentation and the absence of other systemic or dermatological findings, the diagnosis of chevron nails was made.

Discussion

Chevron nails, also known as V-shaped nails or herringbone nails, are an uncommon but benign nail condition typically observed in infancy and early childhood. The condition is characterized by transverse ridges on the nails that converge towards the center, forming a V or chevron shape. This condition was first described by Perry et al. and later by Shuster et al., who explained that the condition might result from axial growth of the nail with synchronous growth occurring from a chevron-shaped growing edge of the nail root. Alternatively, Shuster suggested that sequential growth, with localized variation in the nail production rate, could propagate a wave from the center of the nail to the edge.

The etiology of chevron nails is not well understood, but it is believed to result from temporary disruptions in the nail matrix, possibly related to minor illness or physiological stress during infancy.

In the case of our 7-month-old patient, the history of mild upper respiratory infections might have contributed to the development of chevron nails. However, the lack of other significant illness, skin involvement, or systemic findings supports the benign and self-limiting nature of this condition. Parents were reassured that chevron nails typically resolve on their own as the child grows and that no specific treatment is necessary.
 

Differential Diagnosis

The differential diagnosis of transverse nail changes in children includes other conditions such as trachyonychia, lichen planus, Darier disease, and pachyonychia congenita.

Trachyonychia, also known as “sandpaper nails,” trachyonychia is characterized by the roughening of the nail surface, giving it a dull and ridged appearance. The condition may affect all 20 nails and is often associated with underlying dermatological conditions such as lichen planus or alopecia areata. Unlike chevron nails, trachyonychia presents with more diffuse nail changes and does not typically feature the distinct V-shaped ridging seen in this patient.

Lichen planus is an inflammatory condition that can affect the skin, mucous membranes, and nails. Nail involvement in lichen planus can lead to longitudinal ridging, thinning, and sometimes even complete nail loss. The absence of other characteristic features of lichen planus, such as violaceous papules on the skin or white lacy patterns on mucous membranes (Wickham striae), makes this diagnosis less likely in our patient.

Darier disease, also known as keratosis follicularis, is a genetic disorder characterized by greasy, warty papules primarily on seborrheic areas of the skin, nail abnormalities, and sometimes mucosal involvement. Nail changes in Darier disease include longitudinal red and white streaks, V-shaped notching at the free edge of the nails, and subungual hyperkeratosis. These nail changes are more severe and distinct than the simple transverse ridging seen in chevron nails. The absence of other clinical signs of Darier disease, such as skin papules or characteristic nail notching, makes this diagnosis unlikely in our patient.

Pachyonychia congenita is a rare genetic disorder characterized by thickened nails (pachyonychia), painful plantar keratoderma, and sometimes oral leukokeratosis. The condition typically presents with significant nail thickening and other systemic findings, which were absent in our patient. The distinct pattern of V-shaped ridging observed in chevron nails does not align with the typical presentation of pachyonychia congenita.
 

Next Steps

No specific treatment is required for chevron nails. The condition is typically self-resolving, and the nails usually return to a normal appearance as the child continues to grow. Parents were advised to monitor the nails for any changes or new symptoms and were reassured about the benign nature of the findings. Follow-up was scheduled to ensure the resolution of the condition as the child develops.

Conclusion

Chevron nails are an important consideration in the differential diagnosis of transverse nail ridging in infants and young children. While the condition is benign and self-limiting, it is crucial to differentiate it from other nail dystrophies, such as trachyonychia, lichen planus, Darier disease, and pachyonychia congenita, which may require further investigation or intervention. Awareness of chevron nails can help prevent unnecessary worry and provide reassurance to parents and caregivers.
 

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.

Suggested Reading

Delano S, Belazarian L. Chevron nails: A normal variant in the pediatric population. Pediatr Dermatol. 2014 Jan-Feb;31(1):e24-5. doi: 10.1111/pde.12193.

John JM et al. Chevron nail — An under-recognised normal variant of nail development. Arch Dis Child. 2024 Jul 18;109(8):648. doi: 10.1136/archdischild-2024-326975.

Shuster S. The significance of chevron nails. Br J Dermatol. 1996;135:151–152. doi: 10.1046/j.1365-2133.1996.d01-961.x.

Starace M et al. Nail disorders in children. Skin Appendage Disord. 2018 Oct;4(4):217-229. doi: 10.1159/000486020.

A patient who developed atrial fibrillation resulting from the failure to adjust the levothyroxine dose after rapid, significant weight loss while on the antiobesity drug tirzepatide (Zepbound) serves as a key reminder in managing patients experiencing rapid weight loss, either from antiobesity medications or any other means: Patients taking medications with weight-based dosing need to have their doses closely monitored.

“Failing to monitor and adjust dosing of these [and other] medications during a period of rapid weight loss may lead to supratherapeutic — even toxic — levels, as was seen in this [case],” underscore the authors of an editorial regarding the Teachable Moment case, published in JAMA Internal Medicine.

Toxicities from excessive doses can have a range of detrimental effects. In terms of thyroid medicine, the failure to adjust levothyroxine treatment for hypothyroidism in cases of rapid weight loss can lead to thyrotoxicosis, and in older patients in particular, a resulting thyrotropin level < 0.1 mIU/L is associated with as much as a threefold increased risk for atrial fibrillation, as observed in the report. 
 

Case Demonstrates Risks

The case involved a 62-year-old man with obesity, hypothyroidism, and type 1 diabetes who presented to the emergency department with palpitations, excessive sweating, confusion, fever, and hand tremors. Upon being diagnosed with atrial fibrillation, the patient was immediately treated. 

His medical history revealed the underlying culprit: Six months earlier, the patient had started treatment with the gastric inhibitory polypeptide (GIP)/glucagon-like peptide (GLP) 1 dual agonist tirzepatide. As is typical with the drug, the patient’s weight quickly plummeted, dropping from a starting body mass index of 44.4 down to 31.2 after 6 months and a decrease in body weight from 132 kg to 93 kg (a loss of 39 kg [approximately 86 lb]).

Despite the substantial change in body weight, his initial dose of 200 µg of levothyroxine, received for hypothyroidism, was not adjusted.

When he was prescribed tirzepatide, 2.5 mg weekly, for obesity, the patient had been recommended to increase the dose every 4 weeks as tolerated and, importantly, to have a follow-up visit in a month. But because he lived in different states seasonally, the follow-up never occurred.

Upon his emergency department visit, the patient’s thyrotropin level had dropped from 1.9 mIU/L at the first visit 6 months earlier to 0.001 mIU/L (well within the atrial fibrillation risk range), and his free thyroxine level (fT4) was 7.26 ng/ dL — substantially outside of the normal range of about 0.9-1.7 ng/dL for adults. 

“The patient had 4-times higher fT4 levels of the upper limit,” first author Kagan E. Karakus, MD, of the Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, told this news organization. “That is why he had experienced the adverse event of atrial fibrillation.”
 

Thyrotoxicosis Symptoms Can Be ‘Insidious,’ Levothyroxine Should Be Monitored

Although tirzepatide has not been approved by the US Food and Drug Administration for the treatment of type 1 diabetes, obesity is on the rise among patients with this disorder and recent research has shown a more than 10% reduction in body weight in 6 months and significant reductions in A1c with various doses. 

Of note, in the current case, although the patient’s levothyroxine dose was not adjusted, his insulin dose was gradually self-decreased during his tirzepatide treatment to prevent hypoglycemia.

“If insulin treatment is excessive in diabetes, it causes hypoglycemia, [and] people with type 1 diabetes will recognize the signs of hypoglycemia related to excessive insulin earlier,” Dr. Karakus said.

If symptoms appear, patients can reduce their insulin doses on their own; however, the symptoms of thyrotoxicosis caused by excessive levothyroxine can be more insidious compared with hypoglycemia, he explained. 

“Although patients can change their insulin doses, they cannot change the levothyroxine doses since it requires a blood test [thyroid-stimulating hormone; TSH] and a new prescription of the new dose.”

The key lesson is that “following levothyroxine treatment initiation or dose adjustment, 4-6 weeks is the optimal duration to recheck [the] thyrotropin level and adjust the dose as needed,” Dr. Karakus said.
 

Key Medications to Monitor

Other common outpatient medications that should be closely monitored in patients experiencing rapid weight loss, by any method, range from anticoagulants, anticonvulsants, and antituberculosis drugs to antibiotics and antifungals, the authors note.

Of note, medications with a narrow therapeutic index include phenytoin, warfarin, lithium carbonate, digoxin theophylline, tacrolimus, valproic acid, carbamazepine, and cyclosporine.

The failure to make necessary dose adjustments “is seen more often since the newer antiobesity drugs reduce a great amount of weight within months, almost as rapidly as bariatric surgery,” Dr. Karakus said.

“It is very important for physicians to be aware of the weight-based medications and narrow therapeutic index medications since their doses should be adjusted carefully, especially during weight loss,” he added.

Furthermore, “the patient should also know that weight reduction medication may cause adverse effects like nausea, vomiting and also may affect metabolism of other medications such that some medication doses should be adjusted regularly.”

In the editorial published with the study, Tyrone A. Johnson, MD, of the Department of Medicine, University of California, San Francisco, and colleagues note that the need for close monitoring is particularly important with older patients, who, in addition to having a higher likelihood of comorbidities, commonly have polypharmacy that could increase the potential for adverse effects.

Another key area concern is the emergence of direct-to-consumer avenues for GLP-1/GIP agonists for the many who either cannot afford or do not have access to the drugs, providing further opportunities for treatment without appropriate clinical oversight, they add.

Overall, the case “highlights the potential dangers underlying under-supervised prescribing of GLP-1/GIP receptor agonists and affirms the need for strong partnerships between patients and their clinicians during their use,” they wrote. 

“These medications are best used in collaboration with continuity care teams, in context of a patient’s entire health, and in comprehensive risk-benefit assessment throughout the entire duration of treatment.”
 

A Caveat: Subclinical Levothyroxine Dosing

Commenting on the study, Matthew Ettleson, MD, a clinical instructor of medicine in the Section of Endocrinology, Diabetes, & Metabolism, University of Chicago, noted the important caveat that patients with hypothyroidism are commonly on subclinical doses, with varying dose adjustment needs.

“The patient in the case was clearly on a replacement level dose. However, many patients are on low doses of levothyroxine (75 µg or lower) for subclinical hypothyroidism, and, in general, I think the risks are lower with patients with subclinical hypothyroidism on lower doses of levothyroxine,” he told this news organization.

Because of that, “frequent TSH monitoring may be excessive in this population,” he said. “I would hesitate to empirically lower the dose with weight loss, unless it was clear that the patient was unlikely to follow up.

“Checking TSH at a more frequent interval and adjusting the dose accordingly should be adequate to prevent situations like this case.”

Dr. Karakus, Dr. Ettleson, and the editorial authors had no relevant disclosures to report.
 

A version of this article appeared on Medscape.com.

A patient who developed atrial fibrillation resulting from the failure to adjust the levothyroxine dose after rapid, significant weight loss while on the antiobesity drug tirzepatide (Zepbound) serves as a key reminder in managing patients experiencing rapid weight loss, either from antiobesity medications or any other means: Patients taking medications with weight-based dosing need to have their doses closely monitored.

“Failing to monitor and adjust dosing of these [and other] medications during a period of rapid weight loss may lead to supratherapeutic — even toxic — levels, as was seen in this [case],” underscore the authors of an editorial regarding the Teachable Moment case, published in JAMA Internal Medicine.

Toxicities from excessive doses can have a range of detrimental effects. In terms of thyroid medicine, the failure to adjust levothyroxine treatment for hypothyroidism in cases of rapid weight loss can lead to thyrotoxicosis, and in older patients in particular, a resulting thyrotropin level < 0.1 mIU/L is associated with as much as a threefold increased risk for atrial fibrillation, as observed in the report. 
 

Case Demonstrates Risks

The case involved a 62-year-old man with obesity, hypothyroidism, and type 1 diabetes who presented to the emergency department with palpitations, excessive sweating, confusion, fever, and hand tremors. Upon being diagnosed with atrial fibrillation, the patient was immediately treated. 

His medical history revealed the underlying culprit: Six months earlier, the patient had started treatment with the gastric inhibitory polypeptide (GIP)/glucagon-like peptide (GLP) 1 dual agonist tirzepatide. As is typical with the drug, the patient’s weight quickly plummeted, dropping from a starting body mass index of 44.4 down to 31.2 after 6 months and a decrease in body weight from 132 kg to 93 kg (a loss of 39 kg [approximately 86 lb]).

Despite the substantial change in body weight, his initial dose of 200 µg of levothyroxine, received for hypothyroidism, was not adjusted.

When he was prescribed tirzepatide, 2.5 mg weekly, for obesity, the patient had been recommended to increase the dose every 4 weeks as tolerated and, importantly, to have a follow-up visit in a month. But because he lived in different states seasonally, the follow-up never occurred.

Upon his emergency department visit, the patient’s thyrotropin level had dropped from 1.9 mIU/L at the first visit 6 months earlier to 0.001 mIU/L (well within the atrial fibrillation risk range), and his free thyroxine level (fT4) was 7.26 ng/ dL — substantially outside of the normal range of about 0.9-1.7 ng/dL for adults. 

“The patient had 4-times higher fT4 levels of the upper limit,” first author Kagan E. Karakus, MD, of the Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, told this news organization. “That is why he had experienced the adverse event of atrial fibrillation.”
 

Thyrotoxicosis Symptoms Can Be ‘Insidious,’ Levothyroxine Should Be Monitored

Although tirzepatide has not been approved by the US Food and Drug Administration for the treatment of type 1 diabetes, obesity is on the rise among patients with this disorder and recent research has shown a more than 10% reduction in body weight in 6 months and significant reductions in A1c with various doses. 

Of note, in the current case, although the patient’s levothyroxine dose was not adjusted, his insulin dose was gradually self-decreased during his tirzepatide treatment to prevent hypoglycemia.

“If insulin treatment is excessive in diabetes, it causes hypoglycemia, [and] people with type 1 diabetes will recognize the signs of hypoglycemia related to excessive insulin earlier,” Dr. Karakus said.

If symptoms appear, patients can reduce their insulin doses on their own; however, the symptoms of thyrotoxicosis caused by excessive levothyroxine can be more insidious compared with hypoglycemia, he explained. 

“Although patients can change their insulin doses, they cannot change the levothyroxine doses since it requires a blood test [thyroid-stimulating hormone; TSH] and a new prescription of the new dose.”

The key lesson is that “following levothyroxine treatment initiation or dose adjustment, 4-6 weeks is the optimal duration to recheck [the] thyrotropin level and adjust the dose as needed,” Dr. Karakus said.
 

Key Medications to Monitor

Other common outpatient medications that should be closely monitored in patients experiencing rapid weight loss, by any method, range from anticoagulants, anticonvulsants, and antituberculosis drugs to antibiotics and antifungals, the authors note.

Of note, medications with a narrow therapeutic index include phenytoin, warfarin, lithium carbonate, digoxin theophylline, tacrolimus, valproic acid, carbamazepine, and cyclosporine.

The failure to make necessary dose adjustments “is seen more often since the newer antiobesity drugs reduce a great amount of weight within months, almost as rapidly as bariatric surgery,” Dr. Karakus said.

“It is very important for physicians to be aware of the weight-based medications and narrow therapeutic index medications since their doses should be adjusted carefully, especially during weight loss,” he added.

Furthermore, “the patient should also know that weight reduction medication may cause adverse effects like nausea, vomiting and also may affect metabolism of other medications such that some medication doses should be adjusted regularly.”

In the editorial published with the study, Tyrone A. Johnson, MD, of the Department of Medicine, University of California, San Francisco, and colleagues note that the need for close monitoring is particularly important with older patients, who, in addition to having a higher likelihood of comorbidities, commonly have polypharmacy that could increase the potential for adverse effects.

Another key area concern is the emergence of direct-to-consumer avenues for GLP-1/GIP agonists for the many who either cannot afford or do not have access to the drugs, providing further opportunities for treatment without appropriate clinical oversight, they add.

Overall, the case “highlights the potential dangers underlying under-supervised prescribing of GLP-1/GIP receptor agonists and affirms the need for strong partnerships between patients and their clinicians during their use,” they wrote. 

“These medications are best used in collaboration with continuity care teams, in context of a patient’s entire health, and in comprehensive risk-benefit assessment throughout the entire duration of treatment.”
 

A Caveat: Subclinical Levothyroxine Dosing

Commenting on the study, Matthew Ettleson, MD, a clinical instructor of medicine in the Section of Endocrinology, Diabetes, & Metabolism, University of Chicago, noted the important caveat that patients with hypothyroidism are commonly on subclinical doses, with varying dose adjustment needs.

“The patient in the case was clearly on a replacement level dose. However, many patients are on low doses of levothyroxine (75 µg or lower) for subclinical hypothyroidism, and, in general, I think the risks are lower with patients with subclinical hypothyroidism on lower doses of levothyroxine,” he told this news organization.

Because of that, “frequent TSH monitoring may be excessive in this population,” he said. “I would hesitate to empirically lower the dose with weight loss, unless it was clear that the patient was unlikely to follow up.

“Checking TSH at a more frequent interval and adjusting the dose accordingly should be adequate to prevent situations like this case.”

Dr. Karakus, Dr. Ettleson, and the editorial authors had no relevant disclosures to report.
 

A version of this article appeared on Medscape.com.

A patient who developed atrial fibrillation resulting from the failure to adjust the levothyroxine dose after rapid, significant weight loss while on the antiobesity drug tirzepatide (Zepbound) serves as a key reminder in managing patients experiencing rapid weight loss, either from antiobesity medications or any other means: Patients taking medications with weight-based dosing need to have their doses closely monitored.

“Failing to monitor and adjust dosing of these [and other] medications during a period of rapid weight loss may lead to supratherapeutic — even toxic — levels, as was seen in this [case],” underscore the authors of an editorial regarding the Teachable Moment case, published in JAMA Internal Medicine.

Toxicities from excessive doses can have a range of detrimental effects. In terms of thyroid medicine, the failure to adjust levothyroxine treatment for hypothyroidism in cases of rapid weight loss can lead to thyrotoxicosis, and in older patients in particular, a resulting thyrotropin level < 0.1 mIU/L is associated with as much as a threefold increased risk for atrial fibrillation, as observed in the report. 
 

Case Demonstrates Risks

The case involved a 62-year-old man with obesity, hypothyroidism, and type 1 diabetes who presented to the emergency department with palpitations, excessive sweating, confusion, fever, and hand tremors. Upon being diagnosed with atrial fibrillation, the patient was immediately treated. 

His medical history revealed the underlying culprit: Six months earlier, the patient had started treatment with the gastric inhibitory polypeptide (GIP)/glucagon-like peptide (GLP) 1 dual agonist tirzepatide. As is typical with the drug, the patient’s weight quickly plummeted, dropping from a starting body mass index of 44.4 down to 31.2 after 6 months and a decrease in body weight from 132 kg to 93 kg (a loss of 39 kg [approximately 86 lb]).

Despite the substantial change in body weight, his initial dose of 200 µg of levothyroxine, received for hypothyroidism, was not adjusted.

When he was prescribed tirzepatide, 2.5 mg weekly, for obesity, the patient had been recommended to increase the dose every 4 weeks as tolerated and, importantly, to have a follow-up visit in a month. But because he lived in different states seasonally, the follow-up never occurred.

Upon his emergency department visit, the patient’s thyrotropin level had dropped from 1.9 mIU/L at the first visit 6 months earlier to 0.001 mIU/L (well within the atrial fibrillation risk range), and his free thyroxine level (fT4) was 7.26 ng/ dL — substantially outside of the normal range of about 0.9-1.7 ng/dL for adults. 

“The patient had 4-times higher fT4 levels of the upper limit,” first author Kagan E. Karakus, MD, of the Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, told this news organization. “That is why he had experienced the adverse event of atrial fibrillation.”
 

Thyrotoxicosis Symptoms Can Be ‘Insidious,’ Levothyroxine Should Be Monitored

Although tirzepatide has not been approved by the US Food and Drug Administration for the treatment of type 1 diabetes, obesity is on the rise among patients with this disorder and recent research has shown a more than 10% reduction in body weight in 6 months and significant reductions in A1c with various doses. 

Of note, in the current case, although the patient’s levothyroxine dose was not adjusted, his insulin dose was gradually self-decreased during his tirzepatide treatment to prevent hypoglycemia.

“If insulin treatment is excessive in diabetes, it causes hypoglycemia, [and] people with type 1 diabetes will recognize the signs of hypoglycemia related to excessive insulin earlier,” Dr. Karakus said.

If symptoms appear, patients can reduce their insulin doses on their own; however, the symptoms of thyrotoxicosis caused by excessive levothyroxine can be more insidious compared with hypoglycemia, he explained. 

“Although patients can change their insulin doses, they cannot change the levothyroxine doses since it requires a blood test [thyroid-stimulating hormone; TSH] and a new prescription of the new dose.”

The key lesson is that “following levothyroxine treatment initiation or dose adjustment, 4-6 weeks is the optimal duration to recheck [the] thyrotropin level and adjust the dose as needed,” Dr. Karakus said.
 

Key Medications to Monitor

Other common outpatient medications that should be closely monitored in patients experiencing rapid weight loss, by any method, range from anticoagulants, anticonvulsants, and antituberculosis drugs to antibiotics and antifungals, the authors note.

Of note, medications with a narrow therapeutic index include phenytoin, warfarin, lithium carbonate, digoxin theophylline, tacrolimus, valproic acid, carbamazepine, and cyclosporine.

The failure to make necessary dose adjustments “is seen more often since the newer antiobesity drugs reduce a great amount of weight within months, almost as rapidly as bariatric surgery,” Dr. Karakus said.

“It is very important for physicians to be aware of the weight-based medications and narrow therapeutic index medications since their doses should be adjusted carefully, especially during weight loss,” he added.

Furthermore, “the patient should also know that weight reduction medication may cause adverse effects like nausea, vomiting and also may affect metabolism of other medications such that some medication doses should be adjusted regularly.”

In the editorial published with the study, Tyrone A. Johnson, MD, of the Department of Medicine, University of California, San Francisco, and colleagues note that the need for close monitoring is particularly important with older patients, who, in addition to having a higher likelihood of comorbidities, commonly have polypharmacy that could increase the potential for adverse effects.

Another key area concern is the emergence of direct-to-consumer avenues for GLP-1/GIP agonists for the many who either cannot afford or do not have access to the drugs, providing further opportunities for treatment without appropriate clinical oversight, they add.

Overall, the case “highlights the potential dangers underlying under-supervised prescribing of GLP-1/GIP receptor agonists and affirms the need for strong partnerships between patients and their clinicians during their use,” they wrote. 

“These medications are best used in collaboration with continuity care teams, in context of a patient’s entire health, and in comprehensive risk-benefit assessment throughout the entire duration of treatment.”
 

A Caveat: Subclinical Levothyroxine Dosing

Commenting on the study, Matthew Ettleson, MD, a clinical instructor of medicine in the Section of Endocrinology, Diabetes, & Metabolism, University of Chicago, noted the important caveat that patients with hypothyroidism are commonly on subclinical doses, with varying dose adjustment needs.

“The patient in the case was clearly on a replacement level dose. However, many patients are on low doses of levothyroxine (75 µg or lower) for subclinical hypothyroidism, and, in general, I think the risks are lower with patients with subclinical hypothyroidism on lower doses of levothyroxine,” he told this news organization.

Because of that, “frequent TSH monitoring may be excessive in this population,” he said. “I would hesitate to empirically lower the dose with weight loss, unless it was clear that the patient was unlikely to follow up.

“Checking TSH at a more frequent interval and adjusting the dose accordingly should be adequate to prevent situations like this case.”

Dr. Karakus, Dr. Ettleson, and the editorial authors had no relevant disclosures to report.
 

A version of this article appeared on Medscape.com.