Federal Practitioner

Attention should be paid to changing a tolerated medication to another within its class. Many drugs approved by the US Food and Drug Administration (FDA), have equivalent therapeutic properties as existing drugs. Rarely do such medications share the same potency and adverse effect (AE) profile.

Case Presentation

A 77-year-old man presented to the emergency department (ED) at the Raymond G. Murphy Medical Center in Albuquerque, New Mexico, with a 1-month history of progressive muscle weakness, which was so severe that he required assistance rising from chairs. The symptoms began when he switched from atorvastatin 40 mg daily to rosuvastatin 40 mg daily. A nephrology consultation was requested for an elevated plasma creatinine.

The patient reported strict adherence to his prescribed medications. In the days following the switch to rosuvastatin, he noticed that his urine turned black. He described the color as “like burnt coffee.” The color gradually cleared before his ED presentation. The patient stopped taking rosuvastatin the day prior to presentation and noted improvement of his symptoms. Review of symptoms was significant for lower extremity paresthesia and numbness the day he started rosuvastatin. He had no symptoms of decompensated heart failure and no recent exacerbations requiring alteration of his diuretic regimen.

The patient’s medical history was significant for traumatic brain injury with complex partial seizures, carpal tunnel syndrome, dyslipidemia, coronary artery disease with percutaneous intervention to the right coronary artery in the late 1990s, atrial fibrillation and ventricular tachycardia, status post implantable cardioverter defibrillator, heart failure with reduced ejection fraction (25%) attributed to ischemic cardiomyopathy, hypertension, lower urinary tract symptoms/prostatism, and previous bladder cancer. In the mid-1960s, the patient served in the US Army and had been deployed to South Korea. After the service, he worked for the local city government. He was retired for about 15 years. He reported no tobacco, alcohol, or recreational drug use and no tattoos. He did not require prior blood or blood product transfusions. None of his family members—parents, siblings, or children—had any history of kidney disease.

The patient’s outpatient medications included levetiracetam 750 mg twice daily, melatonin 9 mg at night, menthol 16%/methyl-salicylate 30% topically up to 4 times per day as needed, aspirin 81 mg once daily, fish oil 1000 mg twice daily, amiodarone 400 mg twice daily, hydralazine 20 mg 3 times daily, isosorbide mononitrate 60 mg daily, metoprolol succinate 100 mg daily, and tamsulosin 0.4 mg at night. His vital signs were stable: afebrile (97.5 ºF), normocardic (74 beats per minute), normotensive (118/78 mm Hg), and normoxic (98% on room air). On examination, he appeared elderly, somewhat frail, and chronically ill but in no acute distress. Affect was pleasant and appropriate, attention was high, and his thought process was logical. He had sparse, grey scalp hair. Extraocular movements were intact. Oral mucosa was pink and moist. His back was nontender, and there was no costovertebral tenderness bilaterally. The patient was in no respiratory distress, with a slightly hyperresonant chest to percussion bilaterally, very faint inspiratory basilar crepitant rales (that cleared with repeat inspiration), and was otherwise clear to auscultation throughout. An outline of an implanted pacemaker was evident on the chest under his left clavicle, with a laterally displaced apical impulse. The rate was normal and the rhythm was regular. Upper extremities demonstrated papyraceous skin but without cyanosis, clubbing, or edema. Radial pulses were slightly diminished. He had no lower extremity edema.

His laboratory values are provided in Table 1. Kidney function was stable months prior to admission. Of note, the blood urea nitrogen and plasma creatinine were increased from his baseline up to 47 and 5.89 mg/dL, respectively. The serum glutamic-oxaloacetic transaminase and serum glutamic pyruvic transaminase were 1051 U/L and 408 U/L, respectively. Plasma amylase and lipase levels also were elevated, 230 U/L and 892 U/L, respectively. Creatine kinase was 41,099 U/L. Urinalysis demonstrated a specific gravity of 1.017, pH of 5, and a large amount of blood (92 red blood cells/high power field).

Discussion

Statin-class drugs inhibit the HMG-CoA reductase (Table 2). Upregulation of low-density lipoprotein cholesterol (LDL-C) receptors in the liver result in increased LDL-C uptake and cholesterol catabolism.¹ Prescribed inhibitors of the HMG-CoA reductase—statins—are known to reduce mortality due to cardiovascular disease (CVD). Much like any other pharmaceutical agent with any measurable potency, HMG-CoA inhibitors can have AEs. Statin therapy has been associated with pancreatitis.² Muscle toxicity is a complication of HMG-CoA reductase inhibitors, and statin-associated symptoms are a leading cause of nonadherence.³ Rosuvastatin had higher AE and drug reactions compared with that of atorvastatin and pitavastatin (35.6%, 8.7%, and 22.2%, respectively) in clinical trials for approval.⁴ We have reported concomitant adermatopathic dermatomyositis with statin-induced myopathy in a 48-year-old man from simvastatin (40 to 80 mg daily).¹

Toxin-induced myopathy should be considered early in the differential diagnosis of weakness.⁵ All HMG-CoA inhibitors have been associated with acute kidney injury, particularly at high doses and also are known to induce myopathies, sometimes with inclusion bodies.¹ Muscle-related AEs correlate with the potency of an HMG-CoA reductase inhibitor according to an analysis using the FDA AE Reporting System (AERS).⁶ Myalgia and rhabdomyolysis are well-known AEs of this class of medications. Furthermore, type II muscle atrophy—particularly in the proximal limb muscles—has been reported.⁵ Patients may have difficulty rising from chairs.¹ Rosuvastatin had the strongest signal for muscular AEs (eg, myalgia, rhabdomyolysis, increased creatine phosphokinase level) from an FDA analysis of AERS.⁷

Rosuvastatin is the only HMG-CoA reductase inhibitor that causes dose-dependent increases in proteinuria and hematuria (Figure 4).⁸ Rosuvastatin at a 5-mg dose may induce 4 times the proteinuria as a placebo. Typically, other statins potentially reduce proteinuria (without hematuria). Proteinuria may be induced by rosuvastatin even at low doses.⁸ Proteinuria is attributed to how rosuvastatin impacts proximal tubular function.⁹ The drug is transported into the proximal tubule by the organic anion transporter-3. Acute kidney injury has been associated with several statins, including rosuvastatin.^7,10 This may be associated with denuded tubular epithelia, active urinary sediment, acute tubular toxicity, vacuolated epithelial cells, and tubular cell casts. Unlike atorvastatin, the increase in proteinuria and hematuria also is dose dependent.

In patients with renal insufficiency (short of end-stage renal disease [ESRD]), most statins other than rosuvastatin are well tolerated and recommended for reduction of overall and CVD mortality risk. However, these benefits seem to diminish once ESRD is reached. Atorvastatin did not impact CVD mortality in patients with type 2 diabetes mellitus (T2DM) and ESRD (despite decreasing LDL-C).¹¹ The AURORA study randomized 10 mg of statin vs placebo in 2776 maintenance dialysis patients aged 50 to 80 years. Rosuvastatin lowered the LDL-C but did not affect all-cause mortality (13.5 vs 14.0 events per 100 patient-years). Patients randomized to rosuvastatin had more than twice as many unclassified strokes (9 vs 4). Rosuvastatin, although efficacious in reducing LDL-C, had no impact on CVD mortality, nonfatal myocardial infarction, or nonfatal stroke.¹² Post hoc analysis demonstrated that in patients with T2DM with ESRD the hazard ratio for hemorrhagic stroke was 5.2.¹³

Rosuvastatin ranked lower than lovastatin, pravastatin, simvastatin, atorvastatin, and fluvastatin with respect to reduction of all-cause mortality in trials of participants with or without prior coronary artery disease.¹⁴ AEs, such as rhabdomyolysis, proteinuria, nephropathy, renal failure, liver, and muscle toxicity are higher with rosuvastatin than other medications in its class.¹⁵

Conclusions

For patients with existing CVD, standard clinical practice is to encourage increased and regular physical activity, cholesterol-lowering diets, weight loss, and smoking cessation. Hypertension should be treated. Glycemia should be well controlled in the setting of T2DM. β-blockers may be beneficial in those with histories of myocardial infarction or heart failure with reduced systolic function. Statins are a valuable tool in the treatment of dyslipidemia.

Statin-induced muscle symptoms are a major reason for discontinuation and nonadherence.¹⁶ Statin-induced myalgia, myositis, and myopathy have been used interchangeably.¹⁷ Rhabdomyolysis, myalgia, increased creatine kinase, statin myopathy, and immune-mediated necrotizing myopathy are among the clinical phenotypes caused by statins.¹⁷ There are 33,695 serious cases—1808 deaths—reported with rosuvastatin in the FDA AERS as of June 30, 2021. Myalgia, pain in extremity, muscle spasms, pain, and arthralgia top the list of AEs. When statin-induced symptoms occur, adherence is rarely improved by dismissive clinicians.¹⁸

Drugs in the same class often have common therapeutic properties. Potencies and AE profiles are seldom uniform. The decision to add or change the brand of medication within a class should be balanced with considerations for the indication, duplications, simplification, AEs, appropriate dosage, and drug-drug interactions.

Acknowledgments

Brent Wagner is funded by a US Department of Veterans Affairs Merit Award (I01 BX001958), a National Institutes of Health R01 grant (DK-102085), Dialysis Clinic, Inc., and partially supported by the University of New Mexico Brain and Behavioral Health Institute (BBHI 2018-1008, 2020-21-002) and in part by the University of New Mexico’s Signature Program in Cardiovascular and Metabolic Disease (CVMD); and the University of New Mexico School of Medicine Research Allocation Committee (C-2459-RAC, New Mexico Medical Trust). Brent Wagner is an Associate Member to the University of New Mexico Health Sciences Center Autophagy, Inflammation, and Metabolism Center of Biomedical Research Excellence (AIM CoBRE) supported by NIH grant P20GM121176.

Funding

National Institutes of Health Grant R01 DK-102085, Dialysis Clinic Inc., VA Merit Award I01 BX001958, Center for Integrated Nanotechnologies User Agreement 2019AU0120, Brain & Behavioral Health Institute (grants 2018-1008, 2020-21-002), University of New Mexico’s Signature Program in Cardiovascular and Metabolic Disease (CVMD), the University of New Mexico School of Medicine Research Allocation Committee (C-2459-RAC, New Mexico Medical Trust) and a metabolomics voucher from the AIM Center (NIH P20GM121176).

Attention should be paid to changing a tolerated medication to another within its class. Many drugs approved by the US Food and Drug Administration (FDA), have equivalent therapeutic properties as existing drugs. Rarely do such medications share the same potency and adverse effect (AE) profile.

Case Presentation

A 77-year-old man presented to the emergency department (ED) at the Raymond G. Murphy Medical Center in Albuquerque, New Mexico, with a 1-month history of progressive muscle weakness, which was so severe that he required assistance rising from chairs. The symptoms began when he switched from atorvastatin 40 mg daily to rosuvastatin 40 mg daily. A nephrology consultation was requested for an elevated plasma creatinine.

The patient reported strict adherence to his prescribed medications. In the days following the switch to rosuvastatin, he noticed that his urine turned black. He described the color as “like burnt coffee.” The color gradually cleared before his ED presentation. The patient stopped taking rosuvastatin the day prior to presentation and noted improvement of his symptoms. Review of symptoms was significant for lower extremity paresthesia and numbness the day he started rosuvastatin. He had no symptoms of decompensated heart failure and no recent exacerbations requiring alteration of his diuretic regimen.

The patient’s medical history was significant for traumatic brain injury with complex partial seizures, carpal tunnel syndrome, dyslipidemia, coronary artery disease with percutaneous intervention to the right coronary artery in the late 1990s, atrial fibrillation and ventricular tachycardia, status post implantable cardioverter defibrillator, heart failure with reduced ejection fraction (25%) attributed to ischemic cardiomyopathy, hypertension, lower urinary tract symptoms/prostatism, and previous bladder cancer. In the mid-1960s, the patient served in the US Army and had been deployed to South Korea. After the service, he worked for the local city government. He was retired for about 15 years. He reported no tobacco, alcohol, or recreational drug use and no tattoos. He did not require prior blood or blood product transfusions. None of his family members—parents, siblings, or children—had any history of kidney disease.

The patient’s outpatient medications included levetiracetam 750 mg twice daily, melatonin 9 mg at night, menthol 16%/methyl-salicylate 30% topically up to 4 times per day as needed, aspirin 81 mg once daily, fish oil 1000 mg twice daily, amiodarone 400 mg twice daily, hydralazine 20 mg 3 times daily, isosorbide mononitrate 60 mg daily, metoprolol succinate 100 mg daily, and tamsulosin 0.4 mg at night. His vital signs were stable: afebrile (97.5 ºF), normocardic (74 beats per minute), normotensive (118/78 mm Hg), and normoxic (98% on room air). On examination, he appeared elderly, somewhat frail, and chronically ill but in no acute distress. Affect was pleasant and appropriate, attention was high, and his thought process was logical. He had sparse, grey scalp hair. Extraocular movements were intact. Oral mucosa was pink and moist. His back was nontender, and there was no costovertebral tenderness bilaterally. The patient was in no respiratory distress, with a slightly hyperresonant chest to percussion bilaterally, very faint inspiratory basilar crepitant rales (that cleared with repeat inspiration), and was otherwise clear to auscultation throughout. An outline of an implanted pacemaker was evident on the chest under his left clavicle, with a laterally displaced apical impulse. The rate was normal and the rhythm was regular. Upper extremities demonstrated papyraceous skin but without cyanosis, clubbing, or edema. Radial pulses were slightly diminished. He had no lower extremity edema.

His laboratory values are provided in Table 1. Kidney function was stable months prior to admission. Of note, the blood urea nitrogen and plasma creatinine were increased from his baseline up to 47 and 5.89 mg/dL, respectively. The serum glutamic-oxaloacetic transaminase and serum glutamic pyruvic transaminase were 1051 U/L and 408 U/L, respectively. Plasma amylase and lipase levels also were elevated, 230 U/L and 892 U/L, respectively. Creatine kinase was 41,099 U/L. Urinalysis demonstrated a specific gravity of 1.017, pH of 5, and a large amount of blood (92 red blood cells/high power field).

Discussion

Statin-class drugs inhibit the HMG-CoA reductase (Table 2). Upregulation of low-density lipoprotein cholesterol (LDL-C) receptors in the liver result in increased LDL-C uptake and cholesterol catabolism.¹ Prescribed inhibitors of the HMG-CoA reductase—statins—are known to reduce mortality due to cardiovascular disease (CVD). Much like any other pharmaceutical agent with any measurable potency, HMG-CoA inhibitors can have AEs. Statin therapy has been associated with pancreatitis.² Muscle toxicity is a complication of HMG-CoA reductase inhibitors, and statin-associated symptoms are a leading cause of nonadherence.³ Rosuvastatin had higher AE and drug reactions compared with that of atorvastatin and pitavastatin (35.6%, 8.7%, and 22.2%, respectively) in clinical trials for approval.⁴ We have reported concomitant adermatopathic dermatomyositis with statin-induced myopathy in a 48-year-old man from simvastatin (40 to 80 mg daily).¹

Toxin-induced myopathy should be considered early in the differential diagnosis of weakness.⁵ All HMG-CoA inhibitors have been associated with acute kidney injury, particularly at high doses and also are known to induce myopathies, sometimes with inclusion bodies.¹ Muscle-related AEs correlate with the potency of an HMG-CoA reductase inhibitor according to an analysis using the FDA AE Reporting System (AERS).⁶ Myalgia and rhabdomyolysis are well-known AEs of this class of medications. Furthermore, type II muscle atrophy—particularly in the proximal limb muscles—has been reported.⁵ Patients may have difficulty rising from chairs.¹ Rosuvastatin had the strongest signal for muscular AEs (eg, myalgia, rhabdomyolysis, increased creatine phosphokinase level) from an FDA analysis of AERS.⁷

Rosuvastatin is the only HMG-CoA reductase inhibitor that causes dose-dependent increases in proteinuria and hematuria (Figure 4).⁸ Rosuvastatin at a 5-mg dose may induce 4 times the proteinuria as a placebo. Typically, other statins potentially reduce proteinuria (without hematuria). Proteinuria may be induced by rosuvastatin even at low doses.⁸ Proteinuria is attributed to how rosuvastatin impacts proximal tubular function.⁹ The drug is transported into the proximal tubule by the organic anion transporter-3. Acute kidney injury has been associated with several statins, including rosuvastatin.^7,10 This may be associated with denuded tubular epithelia, active urinary sediment, acute tubular toxicity, vacuolated epithelial cells, and tubular cell casts. Unlike atorvastatin, the increase in proteinuria and hematuria also is dose dependent.

In patients with renal insufficiency (short of end-stage renal disease [ESRD]), most statins other than rosuvastatin are well tolerated and recommended for reduction of overall and CVD mortality risk. However, these benefits seem to diminish once ESRD is reached. Atorvastatin did not impact CVD mortality in patients with type 2 diabetes mellitus (T2DM) and ESRD (despite decreasing LDL-C).¹¹ The AURORA study randomized 10 mg of statin vs placebo in 2776 maintenance dialysis patients aged 50 to 80 years. Rosuvastatin lowered the LDL-C but did not affect all-cause mortality (13.5 vs 14.0 events per 100 patient-years). Patients randomized to rosuvastatin had more than twice as many unclassified strokes (9 vs 4). Rosuvastatin, although efficacious in reducing LDL-C, had no impact on CVD mortality, nonfatal myocardial infarction, or nonfatal stroke.¹² Post hoc analysis demonstrated that in patients with T2DM with ESRD the hazard ratio for hemorrhagic stroke was 5.2.¹³

Rosuvastatin ranked lower than lovastatin, pravastatin, simvastatin, atorvastatin, and fluvastatin with respect to reduction of all-cause mortality in trials of participants with or without prior coronary artery disease.¹⁴ AEs, such as rhabdomyolysis, proteinuria, nephropathy, renal failure, liver, and muscle toxicity are higher with rosuvastatin than other medications in its class.¹⁵

Conclusions

For patients with existing CVD, standard clinical practice is to encourage increased and regular physical activity, cholesterol-lowering diets, weight loss, and smoking cessation. Hypertension should be treated. Glycemia should be well controlled in the setting of T2DM. β-blockers may be beneficial in those with histories of myocardial infarction or heart failure with reduced systolic function. Statins are a valuable tool in the treatment of dyslipidemia.

Statin-induced muscle symptoms are a major reason for discontinuation and nonadherence.¹⁶ Statin-induced myalgia, myositis, and myopathy have been used interchangeably.¹⁷ Rhabdomyolysis, myalgia, increased creatine kinase, statin myopathy, and immune-mediated necrotizing myopathy are among the clinical phenotypes caused by statins.¹⁷ There are 33,695 serious cases—1808 deaths—reported with rosuvastatin in the FDA AERS as of June 30, 2021. Myalgia, pain in extremity, muscle spasms, pain, and arthralgia top the list of AEs. When statin-induced symptoms occur, adherence is rarely improved by dismissive clinicians.¹⁸

Drugs in the same class often have common therapeutic properties. Potencies and AE profiles are seldom uniform. The decision to add or change the brand of medication within a class should be balanced with considerations for the indication, duplications, simplification, AEs, appropriate dosage, and drug-drug interactions.

Acknowledgments

Brent Wagner is funded by a US Department of Veterans Affairs Merit Award (I01 BX001958), a National Institutes of Health R01 grant (DK-102085), Dialysis Clinic, Inc., and partially supported by the University of New Mexico Brain and Behavioral Health Institute (BBHI 2018-1008, 2020-21-002) and in part by the University of New Mexico’s Signature Program in Cardiovascular and Metabolic Disease (CVMD); and the University of New Mexico School of Medicine Research Allocation Committee (C-2459-RAC, New Mexico Medical Trust). Brent Wagner is an Associate Member to the University of New Mexico Health Sciences Center Autophagy, Inflammation, and Metabolism Center of Biomedical Research Excellence (AIM CoBRE) supported by NIH grant P20GM121176.

Funding

National Institutes of Health Grant R01 DK-102085, Dialysis Clinic Inc., VA Merit Award I01 BX001958, Center for Integrated Nanotechnologies User Agreement 2019AU0120, Brain & Behavioral Health Institute (grants 2018-1008, 2020-21-002), University of New Mexico’s Signature Program in Cardiovascular and Metabolic Disease (CVMD), the University of New Mexico School of Medicine Research Allocation Committee (C-2459-RAC, New Mexico Medical Trust) and a metabolomics voucher from the AIM Center (NIH P20GM121176).

Attention should be paid to changing a tolerated medication to another within its class. Many drugs approved by the US Food and Drug Administration (FDA), have equivalent therapeutic properties as existing drugs. Rarely do such medications share the same potency and adverse effect (AE) profile.

Case Presentation

A 77-year-old man presented to the emergency department (ED) at the Raymond G. Murphy Medical Center in Albuquerque, New Mexico, with a 1-month history of progressive muscle weakness, which was so severe that he required assistance rising from chairs. The symptoms began when he switched from atorvastatin 40 mg daily to rosuvastatin 40 mg daily. A nephrology consultation was requested for an elevated plasma creatinine.

The patient reported strict adherence to his prescribed medications. In the days following the switch to rosuvastatin, he noticed that his urine turned black. He described the color as “like burnt coffee.” The color gradually cleared before his ED presentation. The patient stopped taking rosuvastatin the day prior to presentation and noted improvement of his symptoms. Review of symptoms was significant for lower extremity paresthesia and numbness the day he started rosuvastatin. He had no symptoms of decompensated heart failure and no recent exacerbations requiring alteration of his diuretic regimen.

The patient’s medical history was significant for traumatic brain injury with complex partial seizures, carpal tunnel syndrome, dyslipidemia, coronary artery disease with percutaneous intervention to the right coronary artery in the late 1990s, atrial fibrillation and ventricular tachycardia, status post implantable cardioverter defibrillator, heart failure with reduced ejection fraction (25%) attributed to ischemic cardiomyopathy, hypertension, lower urinary tract symptoms/prostatism, and previous bladder cancer. In the mid-1960s, the patient served in the US Army and had been deployed to South Korea. After the service, he worked for the local city government. He was retired for about 15 years. He reported no tobacco, alcohol, or recreational drug use and no tattoos. He did not require prior blood or blood product transfusions. None of his family members—parents, siblings, or children—had any history of kidney disease.

The patient’s outpatient medications included levetiracetam 750 mg twice daily, melatonin 9 mg at night, menthol 16%/methyl-salicylate 30% topically up to 4 times per day as needed, aspirin 81 mg once daily, fish oil 1000 mg twice daily, amiodarone 400 mg twice daily, hydralazine 20 mg 3 times daily, isosorbide mononitrate 60 mg daily, metoprolol succinate 100 mg daily, and tamsulosin 0.4 mg at night. His vital signs were stable: afebrile (97.5 ºF), normocardic (74 beats per minute), normotensive (118/78 mm Hg), and normoxic (98% on room air). On examination, he appeared elderly, somewhat frail, and chronically ill but in no acute distress. Affect was pleasant and appropriate, attention was high, and his thought process was logical. He had sparse, grey scalp hair. Extraocular movements were intact. Oral mucosa was pink and moist. His back was nontender, and there was no costovertebral tenderness bilaterally. The patient was in no respiratory distress, with a slightly hyperresonant chest to percussion bilaterally, very faint inspiratory basilar crepitant rales (that cleared with repeat inspiration), and was otherwise clear to auscultation throughout. An outline of an implanted pacemaker was evident on the chest under his left clavicle, with a laterally displaced apical impulse. The rate was normal and the rhythm was regular. Upper extremities demonstrated papyraceous skin but without cyanosis, clubbing, or edema. Radial pulses were slightly diminished. He had no lower extremity edema.

His laboratory values are provided in Table 1. Kidney function was stable months prior to admission. Of note, the blood urea nitrogen and plasma creatinine were increased from his baseline up to 47 and 5.89 mg/dL, respectively. The serum glutamic-oxaloacetic transaminase and serum glutamic pyruvic transaminase were 1051 U/L and 408 U/L, respectively. Plasma amylase and lipase levels also were elevated, 230 U/L and 892 U/L, respectively. Creatine kinase was 41,099 U/L. Urinalysis demonstrated a specific gravity of 1.017, pH of 5, and a large amount of blood (92 red blood cells/high power field).

Discussion

Statin-class drugs inhibit the HMG-CoA reductase (Table 2). Upregulation of low-density lipoprotein cholesterol (LDL-C) receptors in the liver result in increased LDL-C uptake and cholesterol catabolism.¹ Prescribed inhibitors of the HMG-CoA reductase—statins—are known to reduce mortality due to cardiovascular disease (CVD). Much like any other pharmaceutical agent with any measurable potency, HMG-CoA inhibitors can have AEs. Statin therapy has been associated with pancreatitis.² Muscle toxicity is a complication of HMG-CoA reductase inhibitors, and statin-associated symptoms are a leading cause of nonadherence.³ Rosuvastatin had higher AE and drug reactions compared with that of atorvastatin and pitavastatin (35.6%, 8.7%, and 22.2%, respectively) in clinical trials for approval.⁴ We have reported concomitant adermatopathic dermatomyositis with statin-induced myopathy in a 48-year-old man from simvastatin (40 to 80 mg daily).¹

Toxin-induced myopathy should be considered early in the differential diagnosis of weakness.⁵ All HMG-CoA inhibitors have been associated with acute kidney injury, particularly at high doses and also are known to induce myopathies, sometimes with inclusion bodies.¹ Muscle-related AEs correlate with the potency of an HMG-CoA reductase inhibitor according to an analysis using the FDA AE Reporting System (AERS).⁶ Myalgia and rhabdomyolysis are well-known AEs of this class of medications. Furthermore, type II muscle atrophy—particularly in the proximal limb muscles—has been reported.⁵ Patients may have difficulty rising from chairs.¹ Rosuvastatin had the strongest signal for muscular AEs (eg, myalgia, rhabdomyolysis, increased creatine phosphokinase level) from an FDA analysis of AERS.⁷

Rosuvastatin is the only HMG-CoA reductase inhibitor that causes dose-dependent increases in proteinuria and hematuria (Figure 4).⁸ Rosuvastatin at a 5-mg dose may induce 4 times the proteinuria as a placebo. Typically, other statins potentially reduce proteinuria (without hematuria). Proteinuria may be induced by rosuvastatin even at low doses.⁸ Proteinuria is attributed to how rosuvastatin impacts proximal tubular function.⁹ The drug is transported into the proximal tubule by the organic anion transporter-3. Acute kidney injury has been associated with several statins, including rosuvastatin.^7,10 This may be associated with denuded tubular epithelia, active urinary sediment, acute tubular toxicity, vacuolated epithelial cells, and tubular cell casts. Unlike atorvastatin, the increase in proteinuria and hematuria also is dose dependent.

In patients with renal insufficiency (short of end-stage renal disease [ESRD]), most statins other than rosuvastatin are well tolerated and recommended for reduction of overall and CVD mortality risk. However, these benefits seem to diminish once ESRD is reached. Atorvastatin did not impact CVD mortality in patients with type 2 diabetes mellitus (T2DM) and ESRD (despite decreasing LDL-C).¹¹ The AURORA study randomized 10 mg of statin vs placebo in 2776 maintenance dialysis patients aged 50 to 80 years. Rosuvastatin lowered the LDL-C but did not affect all-cause mortality (13.5 vs 14.0 events per 100 patient-years). Patients randomized to rosuvastatin had more than twice as many unclassified strokes (9 vs 4). Rosuvastatin, although efficacious in reducing LDL-C, had no impact on CVD mortality, nonfatal myocardial infarction, or nonfatal stroke.¹² Post hoc analysis demonstrated that in patients with T2DM with ESRD the hazard ratio for hemorrhagic stroke was 5.2.¹³

Rosuvastatin ranked lower than lovastatin, pravastatin, simvastatin, atorvastatin, and fluvastatin with respect to reduction of all-cause mortality in trials of participants with or without prior coronary artery disease.¹⁴ AEs, such as rhabdomyolysis, proteinuria, nephropathy, renal failure, liver, and muscle toxicity are higher with rosuvastatin than other medications in its class.¹⁵

Conclusions

For patients with existing CVD, standard clinical practice is to encourage increased and regular physical activity, cholesterol-lowering diets, weight loss, and smoking cessation. Hypertension should be treated. Glycemia should be well controlled in the setting of T2DM. β-blockers may be beneficial in those with histories of myocardial infarction or heart failure with reduced systolic function. Statins are a valuable tool in the treatment of dyslipidemia.

Statin-induced muscle symptoms are a major reason for discontinuation and nonadherence.¹⁶ Statin-induced myalgia, myositis, and myopathy have been used interchangeably.¹⁷ Rhabdomyolysis, myalgia, increased creatine kinase, statin myopathy, and immune-mediated necrotizing myopathy are among the clinical phenotypes caused by statins.¹⁷ There are 33,695 serious cases—1808 deaths—reported with rosuvastatin in the FDA AERS as of June 30, 2021. Myalgia, pain in extremity, muscle spasms, pain, and arthralgia top the list of AEs. When statin-induced symptoms occur, adherence is rarely improved by dismissive clinicians.¹⁸

Drugs in the same class often have common therapeutic properties. Potencies and AE profiles are seldom uniform. The decision to add or change the brand of medication within a class should be balanced with considerations for the indication, duplications, simplification, AEs, appropriate dosage, and drug-drug interactions.

Acknowledgments

Brent Wagner is funded by a US Department of Veterans Affairs Merit Award (I01 BX001958), a National Institutes of Health R01 grant (DK-102085), Dialysis Clinic, Inc., and partially supported by the University of New Mexico Brain and Behavioral Health Institute (BBHI 2018-1008, 2020-21-002) and in part by the University of New Mexico’s Signature Program in Cardiovascular and Metabolic Disease (CVMD); and the University of New Mexico School of Medicine Research Allocation Committee (C-2459-RAC, New Mexico Medical Trust). Brent Wagner is an Associate Member to the University of New Mexico Health Sciences Center Autophagy, Inflammation, and Metabolism Center of Biomedical Research Excellence (AIM CoBRE) supported by NIH grant P20GM121176.

Funding

National Institutes of Health Grant R01 DK-102085, Dialysis Clinic Inc., VA Merit Award I01 BX001958, Center for Integrated Nanotechnologies User Agreement 2019AU0120, Brain & Behavioral Health Institute (grants 2018-1008, 2020-21-002), University of New Mexico’s Signature Program in Cardiovascular and Metabolic Disease (CVMD), the University of New Mexico School of Medicine Research Allocation Committee (C-2459-RAC, New Mexico Medical Trust) and a metabolomics voucher from the AIM Center (NIH P20GM121176).

The risk of occult gastric adenocarcinoma is highly prevalent in hereditary lobular breast cancer (HLBC) families who harbor any type of CDH1 variant and this risk remains high in patients with no family history of gastric cancer, a prospective cohort study has shown.

“In short, what we are putting forward with these data is that pathogenic/likely pathogenic (P/LP) variants in the CDH1 gene confer a very high risk, at the very least, of occult early-stage gastric cancer in patients with HLBC,” said Jeremy Davis, MD, of the surgical oncology program, Center for Cancer Research at the National Cancer Institute.

“So patients that are referred to as ‘HLBC’ due to a CDH1 variant should at least undergo annual endoscopic surveillance but the real questions is whether or not they should also consider prophylactic total gastrectomy – as many patients in our study did,” he said.

The study, which was published online Oct. 13, 2021, in JAMA Surgery, included a cohort of 151 families totaling 283 patients with a CDH1 pathogenic or likely pathogenic (P/LP) variant. Analyses were conducted on three patient groups, which included those with HLBC and a family history of breast cancer but no gastric cancer, those with hereditary diffuse gastric cancer (HDGC) but no history of breast cancer, and those with a family history of both gastric and breast cancer in the mixed group. Of these, 15.5% had a history of HLBC, 16.2% had a history of HDGC, and 52.6% made up the mixed group.

“We examined the HLBC group with specific attention to CDH1 genotype and prevalence of occult gastric cancer,” the authors explained. The group consisted of 31 families with 19 CDH1 variants, 10 of which were also present in the HDGC and mixed groups.

Among this group of patients, almost 73% underwent one or more surveillance endoscopies and on endoscopy, occult signet ring cell carcinoma was detected in over one-third of patients.

The median age at the time of endoscopic carcinoma detection was only 33 years.

“Nearly all of the patients with HLBC (93.8%) ... who elected for risk-reducing total gastrectomy owing to their underlying CDH1 P/LP variant harbored occult signet ring cell gastric adenocarcinoma on final pathology,” investigators observed.

The median age at the time patients elected to undergo total gastrectomy was 50 years.

The prevalence of occult gastric cancer among asymptomatic patients in the HDGC group was similarly high, affecting almost 95% of this group of patients.

Some 18 out of 19 CDH1 P/LP variants were responsible for this high prevalence of occult gastric cancer, as the investigators pointed out.

“Hereditary cancer risk is informed by the presence of a germline gene variant more so than by family history of cancer,” the authors stressed. “[And we found that] germline CDH1 P/LP variants appear to have a highly penetrant gastric phenotype irrespective of family history.”

Given this finding, the authors stressed that it is “paramount” patients previously assigned a diagnosis of HLBC not be excluded from undergoing gastric cancer risk assessment and counseling.

Furthermore, “the mere presence of a germline CDH1 P/LP variant, regardless of family history, may be reason enough to consider prophylactic total gastrectomy,” the authors wrote.

Limitations of the study included the fact that the disease phenotype was established from family pedigrees which has the potential for recall bias by family members.

The study was supported in part by the Intramural Research Program of the National Cancer Institute. None of the authors had conflicts of interest to disclose.

The risk of occult gastric adenocarcinoma is highly prevalent in hereditary lobular breast cancer (HLBC) families who harbor any type of CDH1 variant and this risk remains high in patients with no family history of gastric cancer, a prospective cohort study has shown.

“In short, what we are putting forward with these data is that pathogenic/likely pathogenic (P/LP) variants in the CDH1 gene confer a very high risk, at the very least, of occult early-stage gastric cancer in patients with HLBC,” said Jeremy Davis, MD, of the surgical oncology program, Center for Cancer Research at the National Cancer Institute.

“So patients that are referred to as ‘HLBC’ due to a CDH1 variant should at least undergo annual endoscopic surveillance but the real questions is whether or not they should also consider prophylactic total gastrectomy – as many patients in our study did,” he said.

The study, which was published online Oct. 13, 2021, in JAMA Surgery, included a cohort of 151 families totaling 283 patients with a CDH1 pathogenic or likely pathogenic (P/LP) variant. Analyses were conducted on three patient groups, which included those with HLBC and a family history of breast cancer but no gastric cancer, those with hereditary diffuse gastric cancer (HDGC) but no history of breast cancer, and those with a family history of both gastric and breast cancer in the mixed group. Of these, 15.5% had a history of HLBC, 16.2% had a history of HDGC, and 52.6% made up the mixed group.

“We examined the HLBC group with specific attention to CDH1 genotype and prevalence of occult gastric cancer,” the authors explained. The group consisted of 31 families with 19 CDH1 variants, 10 of which were also present in the HDGC and mixed groups.

Among this group of patients, almost 73% underwent one or more surveillance endoscopies and on endoscopy, occult signet ring cell carcinoma was detected in over one-third of patients.

The median age at the time of endoscopic carcinoma detection was only 33 years.

“Nearly all of the patients with HLBC (93.8%) ... who elected for risk-reducing total gastrectomy owing to their underlying CDH1 P/LP variant harbored occult signet ring cell gastric adenocarcinoma on final pathology,” investigators observed.

The median age at the time patients elected to undergo total gastrectomy was 50 years.

The prevalence of occult gastric cancer among asymptomatic patients in the HDGC group was similarly high, affecting almost 95% of this group of patients.

Some 18 out of 19 CDH1 P/LP variants were responsible for this high prevalence of occult gastric cancer, as the investigators pointed out.

“Hereditary cancer risk is informed by the presence of a germline gene variant more so than by family history of cancer,” the authors stressed. “[And we found that] germline CDH1 P/LP variants appear to have a highly penetrant gastric phenotype irrespective of family history.”

Given this finding, the authors stressed that it is “paramount” patients previously assigned a diagnosis of HLBC not be excluded from undergoing gastric cancer risk assessment and counseling.

Furthermore, “the mere presence of a germline CDH1 P/LP variant, regardless of family history, may be reason enough to consider prophylactic total gastrectomy,” the authors wrote.

Limitations of the study included the fact that the disease phenotype was established from family pedigrees which has the potential for recall bias by family members.

The study was supported in part by the Intramural Research Program of the National Cancer Institute. None of the authors had conflicts of interest to disclose.

The risk of occult gastric adenocarcinoma is highly prevalent in hereditary lobular breast cancer (HLBC) families who harbor any type of CDH1 variant and this risk remains high in patients with no family history of gastric cancer, a prospective cohort study has shown.

“In short, what we are putting forward with these data is that pathogenic/likely pathogenic (P/LP) variants in the CDH1 gene confer a very high risk, at the very least, of occult early-stage gastric cancer in patients with HLBC,” said Jeremy Davis, MD, of the surgical oncology program, Center for Cancer Research at the National Cancer Institute.

“So patients that are referred to as ‘HLBC’ due to a CDH1 variant should at least undergo annual endoscopic surveillance but the real questions is whether or not they should also consider prophylactic total gastrectomy – as many patients in our study did,” he said.

The study, which was published online Oct. 13, 2021, in JAMA Surgery, included a cohort of 151 families totaling 283 patients with a CDH1 pathogenic or likely pathogenic (P/LP) variant. Analyses were conducted on three patient groups, which included those with HLBC and a family history of breast cancer but no gastric cancer, those with hereditary diffuse gastric cancer (HDGC) but no history of breast cancer, and those with a family history of both gastric and breast cancer in the mixed group. Of these, 15.5% had a history of HLBC, 16.2% had a history of HDGC, and 52.6% made up the mixed group.

“We examined the HLBC group with specific attention to CDH1 genotype and prevalence of occult gastric cancer,” the authors explained. The group consisted of 31 families with 19 CDH1 variants, 10 of which were also present in the HDGC and mixed groups.

Among this group of patients, almost 73% underwent one or more surveillance endoscopies and on endoscopy, occult signet ring cell carcinoma was detected in over one-third of patients.

The median age at the time of endoscopic carcinoma detection was only 33 years.

“Nearly all of the patients with HLBC (93.8%) ... who elected for risk-reducing total gastrectomy owing to their underlying CDH1 P/LP variant harbored occult signet ring cell gastric adenocarcinoma on final pathology,” investigators observed.

The median age at the time patients elected to undergo total gastrectomy was 50 years.

The prevalence of occult gastric cancer among asymptomatic patients in the HDGC group was similarly high, affecting almost 95% of this group of patients.

Some 18 out of 19 CDH1 P/LP variants were responsible for this high prevalence of occult gastric cancer, as the investigators pointed out.

“Hereditary cancer risk is informed by the presence of a germline gene variant more so than by family history of cancer,” the authors stressed. “[And we found that] germline CDH1 P/LP variants appear to have a highly penetrant gastric phenotype irrespective of family history.”

Given this finding, the authors stressed that it is “paramount” patients previously assigned a diagnosis of HLBC not be excluded from undergoing gastric cancer risk assessment and counseling.

Furthermore, “the mere presence of a germline CDH1 P/LP variant, regardless of family history, may be reason enough to consider prophylactic total gastrectomy,” the authors wrote.

Limitations of the study included the fact that the disease phenotype was established from family pedigrees which has the potential for recall bias by family members.

The study was supported in part by the Intramural Research Program of the National Cancer Institute. None of the authors had conflicts of interest to disclose.

Should doctors seeking healthcare disclose that they are a doctor? 

The question drew spirited debate when urologist Ashley Winter, MD, made a simple, straightforward request on Twitter: “If you are a doctor & you come to an appointment please tell me you are a doctor, not because I will treat you differently but because it’s easier to speak in jargon.”

She later added, “This doesn’t’ mean I would be less patient-focused or emotional with a physician or other [healthcare worker]. Just means that, instead of saying ‘you will have a catheter draining your urine to a bag,’ I can say, ‘you will have a Foley.’ ”

The Tweet followed an encounter with a patient who told Dr. Winter that he was a doctor only after she had gone to some length explaining a surgical procedure in lay terms.

“I explained the surgery, obviously assuming he was an intelligent adult, but using fully layman’s terms,” she said in an interview. The patient then told her that he was a doctor. “I guess I felt this embarrassment — I wouldn’t have treated him differently, but I just could have discussed the procedure with him in more professional terms.” 

“To some extent, it was my own fault,” she commented in an interview. “I didn’t take the time to ask [about his work] at the beginning of the consultation, but that’s a fine line, also,” added Dr. Winter, a urologist and sexual medicine physician in Portland, Ore.

“You know that patient is there because they want care from you and it’s not necessarily always at the forefront of importance to be asking them what they do for their work, but alternatively, if you don’t ask then you put them in this position where they have to find a way to go ahead and tell you.”

Several people chimed in on the thread to voice their thoughts on the matter. Some commiserated with Dr. Winter’s experience:

“I took care of a retired cardiologist in the hospital as a second-year resident and honest to god he let me ramble on ‘explaining’ his echo result and never told me. I found out a couple days later and wanted to die,” posted @MaddyAndrewsMD.

Another recalled a similarly embarrassing experience when she “went on and on” discussing headaches with a patient whose husband “was in the corner smirking.”

“They told my attending later [that the] husband was a retired FM doc who practiced medicine longer than I’ve been alive. I wanted to die,” posted @JSinghDO.

Many on the thread, though, were doctors and other healthcare professionals speaking as patients. Some said they didn’t want to disclose their status as a healthcare provider because they felt it affected the care they received.

For example, @drhelenrainford commented: “In my experience my care is less ‘caring’ when they know I am a [doctor]. I get spoken to like they are discussing a patient with me — no empathy just facts and difficult results just blurted out without consideration. Awful awful time as an inpatient …but that’s another story!”

@Dr_B_Ring said: “Nope – You and I speak different jargon – I would want you to speak to me like a human that doesn’t know your jargon. My ego would get in the way of asking about the acronyms I don’t know if you knew I was a fellow physician.”

Conversely, @lozzlemcfozzle said: “Honestly I prefer not to tell my Doctors — I’ve found people skip explanations assuming I ‘know,’ or seem a little nervous when I tell them!”

Others said they felt uncomfortable — pretentious, even — in announcing their status, or worried that they might come across as expecting special care.

“It’s such a tough needle to thread. Want to tell people early but not come off as demanding special treatment, but don’t want to wait too long and it seems like a trap,” said @MDaware.

Twitter user @MsBabyCatcher wrote: “I have a hard time doing this because I don’t want people to think I’m being pretentious or going to micromanage/dictate care.”

Replying to @MsBabyCatcher, @RedStethoscope wrote: “I used to think this too until I got [very poor] care a few times, and was advised by other doctor moms to ‘play the doctor card.’ I have gotten better/more compassionate care by making sure it’s clear that I’m a physician (which is junk, but here we are).”

Several of those responding used the words “tricky” and “awkward,” suggesting a common theme for doctors presenting as patients.

“I struggle with this. My 5-year-old broke her arm this weekend, we spent hours in the ED, of my own hospital, I never mentioned it because I didn’t want to get preferential care. But as they were explaining her type of fracture, it felt awkward and inefficient,” said @lindsay_petty.

To avoid the awkwardness, a number of respondents said they purposefully use medical jargon to open up a conversation rather than just offering up the information that they are a doctor.

Still others offered suggestions on how to broach the subject more directly when presenting as a patient:

‘”Just FYI I’m a X doc but I’m here because I really want your help and advice!” That’s what I usually do,” wrote @drcakefm.

@BeeSting14618 Tweeted: “I usually say ‘I know some of this but I’m here because I want YOUR guidance. Also I may ask dumb questions, and I’ll tell you if a question is asking your opinion or making a request.’”

A few others injected a bit of humor: “I just do the 14-part handshake that only doctors know. Is that not customary?” quipped @Branmiz25.

“Ah yes, that transmits the entire [history of present illness],” replied Dr. Winter.

Jokes aside, the topic is obviously one that touched on a shared experience among healthcare providers, Dr. Winter commented. The Twitter thread she started just “blew up.”

That’s typically a sign that the Tweet is relatable for a lot of people, she said.

“It’s definitely something that all of us as care providers and as patients understand. It’s a funny, awkward thing that can really change an interaction, so we probably all feel pretty strongly about our experiences related to that,” she added.

The debate begs the question: Is there a duty or ethical reason to disclose?

“I definitely think it is very reasonable to disclose that one is a medical professional to another doctor,” medical ethicist Charlotte Blease, PhD, said in an interview. “There are good reasons to believe doing so might make a difference to the quality of communication and transparency.”

If the ability to use medical terminology or jargon more freely improves patient understanding, autonomy, and shared decision-making, then it may be of benefit, said Dr. Blease, a Keane OpenNotes Scholar at Beth Israel Deaconess Medical Center in Boston.

“Since doctors should strive to communicate effectively with every patient and to respect their unique needs and level of understanding, then I see no reason to deny that one is a medic,” she added.”

Knowing how to share the information is another story.

“This is something that affects all of us as physicians — we’re going to be patients at some point, right?” Dr. Winter commented. “But I don’t think how to disclose that is something that was ever brought up in my medical training.”

“Maybe there should just be a discussion of this one day when people are in medical school — maybe in a professionalism course — to broach this topic or look at if there’s any literature on outcomes related to disclosure of status or what are best practices,” she suggested. 

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

Should doctors seeking healthcare disclose that they are a doctor? 

The question drew spirited debate when urologist Ashley Winter, MD, made a simple, straightforward request on Twitter: “If you are a doctor & you come to an appointment please tell me you are a doctor, not because I will treat you differently but because it’s easier to speak in jargon.”

She later added, “This doesn’t’ mean I would be less patient-focused or emotional with a physician or other [healthcare worker]. Just means that, instead of saying ‘you will have a catheter draining your urine to a bag,’ I can say, ‘you will have a Foley.’ ”

The Tweet followed an encounter with a patient who told Dr. Winter that he was a doctor only after she had gone to some length explaining a surgical procedure in lay terms.

“I explained the surgery, obviously assuming he was an intelligent adult, but using fully layman’s terms,” she said in an interview. The patient then told her that he was a doctor. “I guess I felt this embarrassment — I wouldn’t have treated him differently, but I just could have discussed the procedure with him in more professional terms.” 

“To some extent, it was my own fault,” she commented in an interview. “I didn’t take the time to ask [about his work] at the beginning of the consultation, but that’s a fine line, also,” added Dr. Winter, a urologist and sexual medicine physician in Portland, Ore.

“You know that patient is there because they want care from you and it’s not necessarily always at the forefront of importance to be asking them what they do for their work, but alternatively, if you don’t ask then you put them in this position where they have to find a way to go ahead and tell you.”

Several people chimed in on the thread to voice their thoughts on the matter. Some commiserated with Dr. Winter’s experience:

“I took care of a retired cardiologist in the hospital as a second-year resident and honest to god he let me ramble on ‘explaining’ his echo result and never told me. I found out a couple days later and wanted to die,” posted @MaddyAndrewsMD.

Another recalled a similarly embarrassing experience when she “went on and on” discussing headaches with a patient whose husband “was in the corner smirking.”

“They told my attending later [that the] husband was a retired FM doc who practiced medicine longer than I’ve been alive. I wanted to die,” posted @JSinghDO.

Many on the thread, though, were doctors and other healthcare professionals speaking as patients. Some said they didn’t want to disclose their status as a healthcare provider because they felt it affected the care they received.

For example, @drhelenrainford commented: “In my experience my care is less ‘caring’ when they know I am a [doctor]. I get spoken to like they are discussing a patient with me — no empathy just facts and difficult results just blurted out without consideration. Awful awful time as an inpatient …but that’s another story!”

@Dr_B_Ring said: “Nope – You and I speak different jargon – I would want you to speak to me like a human that doesn’t know your jargon. My ego would get in the way of asking about the acronyms I don’t know if you knew I was a fellow physician.”

Conversely, @lozzlemcfozzle said: “Honestly I prefer not to tell my Doctors — I’ve found people skip explanations assuming I ‘know,’ or seem a little nervous when I tell them!”

Others said they felt uncomfortable — pretentious, even — in announcing their status, or worried that they might come across as expecting special care.

“It’s such a tough needle to thread. Want to tell people early but not come off as demanding special treatment, but don’t want to wait too long and it seems like a trap,” said @MDaware.

Twitter user @MsBabyCatcher wrote: “I have a hard time doing this because I don’t want people to think I’m being pretentious or going to micromanage/dictate care.”

Replying to @MsBabyCatcher, @RedStethoscope wrote: “I used to think this too until I got [very poor] care a few times, and was advised by other doctor moms to ‘play the doctor card.’ I have gotten better/more compassionate care by making sure it’s clear that I’m a physician (which is junk, but here we are).”

Several of those responding used the words “tricky” and “awkward,” suggesting a common theme for doctors presenting as patients.

“I struggle with this. My 5-year-old broke her arm this weekend, we spent hours in the ED, of my own hospital, I never mentioned it because I didn’t want to get preferential care. But as they were explaining her type of fracture, it felt awkward and inefficient,” said @lindsay_petty.

To avoid the awkwardness, a number of respondents said they purposefully use medical jargon to open up a conversation rather than just offering up the information that they are a doctor.

Still others offered suggestions on how to broach the subject more directly when presenting as a patient:

‘”Just FYI I’m a X doc but I’m here because I really want your help and advice!” That’s what I usually do,” wrote @drcakefm.

@BeeSting14618 Tweeted: “I usually say ‘I know some of this but I’m here because I want YOUR guidance. Also I may ask dumb questions, and I’ll tell you if a question is asking your opinion or making a request.’”

A few others injected a bit of humor: “I just do the 14-part handshake that only doctors know. Is that not customary?” quipped @Branmiz25.

“Ah yes, that transmits the entire [history of present illness],” replied Dr. Winter.

Jokes aside, the topic is obviously one that touched on a shared experience among healthcare providers, Dr. Winter commented. The Twitter thread she started just “blew up.”

That’s typically a sign that the Tweet is relatable for a lot of people, she said.

“It’s definitely something that all of us as care providers and as patients understand. It’s a funny, awkward thing that can really change an interaction, so we probably all feel pretty strongly about our experiences related to that,” she added.

The debate begs the question: Is there a duty or ethical reason to disclose?

“I definitely think it is very reasonable to disclose that one is a medical professional to another doctor,” medical ethicist Charlotte Blease, PhD, said in an interview. “There are good reasons to believe doing so might make a difference to the quality of communication and transparency.”

If the ability to use medical terminology or jargon more freely improves patient understanding, autonomy, and shared decision-making, then it may be of benefit, said Dr. Blease, a Keane OpenNotes Scholar at Beth Israel Deaconess Medical Center in Boston.

“Since doctors should strive to communicate effectively with every patient and to respect their unique needs and level of understanding, then I see no reason to deny that one is a medic,” she added.”

Knowing how to share the information is another story.

“This is something that affects all of us as physicians — we’re going to be patients at some point, right?” Dr. Winter commented. “But I don’t think how to disclose that is something that was ever brought up in my medical training.”

“Maybe there should just be a discussion of this one day when people are in medical school — maybe in a professionalism course — to broach this topic or look at if there’s any literature on outcomes related to disclosure of status or what are best practices,” she suggested. 

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

Should doctors seeking healthcare disclose that they are a doctor? 

The question drew spirited debate when urologist Ashley Winter, MD, made a simple, straightforward request on Twitter: “If you are a doctor & you come to an appointment please tell me you are a doctor, not because I will treat you differently but because it’s easier to speak in jargon.”

She later added, “This doesn’t’ mean I would be less patient-focused or emotional with a physician or other [healthcare worker]. Just means that, instead of saying ‘you will have a catheter draining your urine to a bag,’ I can say, ‘you will have a Foley.’ ”

The Tweet followed an encounter with a patient who told Dr. Winter that he was a doctor only after she had gone to some length explaining a surgical procedure in lay terms.

“I explained the surgery, obviously assuming he was an intelligent adult, but using fully layman’s terms,” she said in an interview. The patient then told her that he was a doctor. “I guess I felt this embarrassment — I wouldn’t have treated him differently, but I just could have discussed the procedure with him in more professional terms.” 

“To some extent, it was my own fault,” she commented in an interview. “I didn’t take the time to ask [about his work] at the beginning of the consultation, but that’s a fine line, also,” added Dr. Winter, a urologist and sexual medicine physician in Portland, Ore.

“You know that patient is there because they want care from you and it’s not necessarily always at the forefront of importance to be asking them what they do for their work, but alternatively, if you don’t ask then you put them in this position where they have to find a way to go ahead and tell you.”

Several people chimed in on the thread to voice their thoughts on the matter. Some commiserated with Dr. Winter’s experience:

“I took care of a retired cardiologist in the hospital as a second-year resident and honest to god he let me ramble on ‘explaining’ his echo result and never told me. I found out a couple days later and wanted to die,” posted @MaddyAndrewsMD.

Another recalled a similarly embarrassing experience when she “went on and on” discussing headaches with a patient whose husband “was in the corner smirking.”

“They told my attending later [that the] husband was a retired FM doc who practiced medicine longer than I’ve been alive. I wanted to die,” posted @JSinghDO.

Many on the thread, though, were doctors and other healthcare professionals speaking as patients. Some said they didn’t want to disclose their status as a healthcare provider because they felt it affected the care they received.

For example, @drhelenrainford commented: “In my experience my care is less ‘caring’ when they know I am a [doctor]. I get spoken to like they are discussing a patient with me — no empathy just facts and difficult results just blurted out without consideration. Awful awful time as an inpatient …but that’s another story!”

@Dr_B_Ring said: “Nope – You and I speak different jargon – I would want you to speak to me like a human that doesn’t know your jargon. My ego would get in the way of asking about the acronyms I don’t know if you knew I was a fellow physician.”

Conversely, @lozzlemcfozzle said: “Honestly I prefer not to tell my Doctors — I’ve found people skip explanations assuming I ‘know,’ or seem a little nervous when I tell them!”

Others said they felt uncomfortable — pretentious, even — in announcing their status, or worried that they might come across as expecting special care.

“It’s such a tough needle to thread. Want to tell people early but not come off as demanding special treatment, but don’t want to wait too long and it seems like a trap,” said @MDaware.

Twitter user @MsBabyCatcher wrote: “I have a hard time doing this because I don’t want people to think I’m being pretentious or going to micromanage/dictate care.”

Replying to @MsBabyCatcher, @RedStethoscope wrote: “I used to think this too until I got [very poor] care a few times, and was advised by other doctor moms to ‘play the doctor card.’ I have gotten better/more compassionate care by making sure it’s clear that I’m a physician (which is junk, but here we are).”

Several of those responding used the words “tricky” and “awkward,” suggesting a common theme for doctors presenting as patients.

“I struggle with this. My 5-year-old broke her arm this weekend, we spent hours in the ED, of my own hospital, I never mentioned it because I didn’t want to get preferential care. But as they were explaining her type of fracture, it felt awkward and inefficient,” said @lindsay_petty.

To avoid the awkwardness, a number of respondents said they purposefully use medical jargon to open up a conversation rather than just offering up the information that they are a doctor.

Still others offered suggestions on how to broach the subject more directly when presenting as a patient:

‘”Just FYI I’m a X doc but I’m here because I really want your help and advice!” That’s what I usually do,” wrote @drcakefm.

@BeeSting14618 Tweeted: “I usually say ‘I know some of this but I’m here because I want YOUR guidance. Also I may ask dumb questions, and I’ll tell you if a question is asking your opinion or making a request.’”

A few others injected a bit of humor: “I just do the 14-part handshake that only doctors know. Is that not customary?” quipped @Branmiz25.

“Ah yes, that transmits the entire [history of present illness],” replied Dr. Winter.

Jokes aside, the topic is obviously one that touched on a shared experience among healthcare providers, Dr. Winter commented. The Twitter thread she started just “blew up.”

That’s typically a sign that the Tweet is relatable for a lot of people, she said.

“It’s definitely something that all of us as care providers and as patients understand. It’s a funny, awkward thing that can really change an interaction, so we probably all feel pretty strongly about our experiences related to that,” she added.

The debate begs the question: Is there a duty or ethical reason to disclose?

“I definitely think it is very reasonable to disclose that one is a medical professional to another doctor,” medical ethicist Charlotte Blease, PhD, said in an interview. “There are good reasons to believe doing so might make a difference to the quality of communication and transparency.”

If the ability to use medical terminology or jargon more freely improves patient understanding, autonomy, and shared decision-making, then it may be of benefit, said Dr. Blease, a Keane OpenNotes Scholar at Beth Israel Deaconess Medical Center in Boston.

“Since doctors should strive to communicate effectively with every patient and to respect their unique needs and level of understanding, then I see no reason to deny that one is a medic,” she added.”

Knowing how to share the information is another story.

“This is something that affects all of us as physicians — we’re going to be patients at some point, right?” Dr. Winter commented. “But I don’t think how to disclose that is something that was ever brought up in my medical training.”

“Maybe there should just be a discussion of this one day when people are in medical school — maybe in a professionalism course — to broach this topic or look at if there’s any literature on outcomes related to disclosure of status or what are best practices,” she suggested. 

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

Endocrine-disrupting chemicals linked to a variety of health problems are abundant in fast foods sold in the United States, such as chicken nuggets, hamburgers, and cheese pizza, new research suggests.

Digital Vision./Thinkstock

The first-of-its-kind study, which measured concentrations of chemicals such as phthalates in foods and gloves from U.S. fast food chains, is also the first to detect the plasticizer DEHT in fast foods.

“We knew from prior research that fast food consumption is linked to higher levels of phthalates in people’s bodies, but our study was novel because we actually collected these food items from fast food places and measured them,” said study author Lariah Edwards, PhD, a postdoctoral research scientist at the Milken Institute School of Public Health, George Washington University, Washington.

“Our research added an additional piece of information to the puzzle,” Dr. Edwards said in an interview.

A class of chemicals used in food packaging and food processing equipment, phthalates such as DEHP and DnBP, can leach out of these items and interfere with hormone production, Dr. Edwards said. They are linked with a wide variety of reproductive, developmental, brain, and immune effects, as well as with childhood obesity, asthma, cancer, and cardiovascular problems.

Meanwhile, nonphthalate or replacement plasticizers have been used in place of phthalates, some of which have been banned in certain products. But these plasticizers aren’t well studied, Dr. Edwards said, making the detection of DEHT in fast foods particularly concerning.

“There’s very limited research out there to understand the human health effects” of DEHT in food, she said, “so we’re being exposed before we understand what it’s doing to our health. It’s almost like we’re setting ourselves up for a big experiment.”

The study was recently published in the Journal of Exposure Science & Environmental Epidemiology .
 

Fast foods containing meat had highest concentrations of chemicals

Dr. Edwards and colleagues obtained 64 food samples, including hamburgers, fries, chicken nuggets, chicken burritos, and cheese pizza, as well as three pairs of unused gloves from six different fast food restaurants in San Antonio.

Using gas chromatography–mass spectrometry, they analyzed the samples for 11 chemicals, including eight phthalates and three replacement plasticizers.

The researchers detected 10 of the 11 chemicals in fast food samples: 81% of foods contained DnBP (di-n-butyl phthalate), and 70% contained DEHP (di(2-ethylhexyl phthalate)). Meanwhile 86% of samples contained replacement plasticizer DEHT (di(2-ethylhexyl terephthalate)).

Overall, fast food samples containing meat — including chicken nuggets, chicken burritos, and hamburgers — contained higher levels of these chemicals, Dr. Edwards noted.

“We know fast food is not the most nutritious, and now we’re seeing these chemicals in it we shouldn’t be exposed to,” she said.

The results also create implications for health equity, Dr. Edwards said, as Black people in the United States report eating more fast foods than other racial and ethnic groups for many reasons, such as longstanding residential segregation.

Many advocacy groups are pushing for stronger regulations on phthalates in foods, she said, and the study can be used to fuel those efforts.

“We’re hoping our findings help people understand what they’re eating and what’s in food,” Dr. Edwards said. “If they want to reduce exposure to phthalates in fast food, they can choose foods without meat in them. But not everyone has the option of reducing fast food consumption — personal choice is important, but policy is what’s going to protect us.”

Dr. Edwards noted that the research was limited by small sample sizes gathered in one U.S. city. Limitations in extraction methods also meant the researchers were able to detect chemicals in gloves only at high concentrations.

“That being said, I do think our results are fairly generalizable,” she added, “because the way fast foods are prepared at these restaurants is fairly consistent.”

The study was funded by the Passport Foundation, Forsythia Foundation, and Marisla Foundation. Dr. Edwards has reported no relevant financial relationships.

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

Endocrine-disrupting chemicals linked to a variety of health problems are abundant in fast foods sold in the United States, such as chicken nuggets, hamburgers, and cheese pizza, new research suggests.

Digital Vision./Thinkstock

The first-of-its-kind study, which measured concentrations of chemicals such as phthalates in foods and gloves from U.S. fast food chains, is also the first to detect the plasticizer DEHT in fast foods.

“We knew from prior research that fast food consumption is linked to higher levels of phthalates in people’s bodies, but our study was novel because we actually collected these food items from fast food places and measured them,” said study author Lariah Edwards, PhD, a postdoctoral research scientist at the Milken Institute School of Public Health, George Washington University, Washington.

“Our research added an additional piece of information to the puzzle,” Dr. Edwards said in an interview.

A class of chemicals used in food packaging and food processing equipment, phthalates such as DEHP and DnBP, can leach out of these items and interfere with hormone production, Dr. Edwards said. They are linked with a wide variety of reproductive, developmental, brain, and immune effects, as well as with childhood obesity, asthma, cancer, and cardiovascular problems.

Meanwhile, nonphthalate or replacement plasticizers have been used in place of phthalates, some of which have been banned in certain products. But these plasticizers aren’t well studied, Dr. Edwards said, making the detection of DEHT in fast foods particularly concerning.

“There’s very limited research out there to understand the human health effects” of DEHT in food, she said, “so we’re being exposed before we understand what it’s doing to our health. It’s almost like we’re setting ourselves up for a big experiment.”

The study was recently published in the Journal of Exposure Science & Environmental Epidemiology .
 

Fast foods containing meat had highest concentrations of chemicals

Dr. Edwards and colleagues obtained 64 food samples, including hamburgers, fries, chicken nuggets, chicken burritos, and cheese pizza, as well as three pairs of unused gloves from six different fast food restaurants in San Antonio.

Using gas chromatography–mass spectrometry, they analyzed the samples for 11 chemicals, including eight phthalates and three replacement plasticizers.

The researchers detected 10 of the 11 chemicals in fast food samples: 81% of foods contained DnBP (di-n-butyl phthalate), and 70% contained DEHP (di(2-ethylhexyl phthalate)). Meanwhile 86% of samples contained replacement plasticizer DEHT (di(2-ethylhexyl terephthalate)).

Overall, fast food samples containing meat — including chicken nuggets, chicken burritos, and hamburgers — contained higher levels of these chemicals, Dr. Edwards noted.

“We know fast food is not the most nutritious, and now we’re seeing these chemicals in it we shouldn’t be exposed to,” she said.

The results also create implications for health equity, Dr. Edwards said, as Black people in the United States report eating more fast foods than other racial and ethnic groups for many reasons, such as longstanding residential segregation.

Many advocacy groups are pushing for stronger regulations on phthalates in foods, she said, and the study can be used to fuel those efforts.

“We’re hoping our findings help people understand what they’re eating and what’s in food,” Dr. Edwards said. “If they want to reduce exposure to phthalates in fast food, they can choose foods without meat in them. But not everyone has the option of reducing fast food consumption — personal choice is important, but policy is what’s going to protect us.”

Dr. Edwards noted that the research was limited by small sample sizes gathered in one U.S. city. Limitations in extraction methods also meant the researchers were able to detect chemicals in gloves only at high concentrations.

“That being said, I do think our results are fairly generalizable,” she added, “because the way fast foods are prepared at these restaurants is fairly consistent.”

The study was funded by the Passport Foundation, Forsythia Foundation, and Marisla Foundation. Dr. Edwards has reported no relevant financial relationships.

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

Endocrine-disrupting chemicals linked to a variety of health problems are abundant in fast foods sold in the United States, such as chicken nuggets, hamburgers, and cheese pizza, new research suggests.

Digital Vision./Thinkstock

The first-of-its-kind study, which measured concentrations of chemicals such as phthalates in foods and gloves from U.S. fast food chains, is also the first to detect the plasticizer DEHT in fast foods.

“We knew from prior research that fast food consumption is linked to higher levels of phthalates in people’s bodies, but our study was novel because we actually collected these food items from fast food places and measured them,” said study author Lariah Edwards, PhD, a postdoctoral research scientist at the Milken Institute School of Public Health, George Washington University, Washington.

“Our research added an additional piece of information to the puzzle,” Dr. Edwards said in an interview.

A class of chemicals used in food packaging and food processing equipment, phthalates such as DEHP and DnBP, can leach out of these items and interfere with hormone production, Dr. Edwards said. They are linked with a wide variety of reproductive, developmental, brain, and immune effects, as well as with childhood obesity, asthma, cancer, and cardiovascular problems.

Meanwhile, nonphthalate or replacement plasticizers have been used in place of phthalates, some of which have been banned in certain products. But these plasticizers aren’t well studied, Dr. Edwards said, making the detection of DEHT in fast foods particularly concerning.

“There’s very limited research out there to understand the human health effects” of DEHT in food, she said, “so we’re being exposed before we understand what it’s doing to our health. It’s almost like we’re setting ourselves up for a big experiment.”

The study was recently published in the Journal of Exposure Science & Environmental Epidemiology .
 

Fast foods containing meat had highest concentrations of chemicals

Dr. Edwards and colleagues obtained 64 food samples, including hamburgers, fries, chicken nuggets, chicken burritos, and cheese pizza, as well as three pairs of unused gloves from six different fast food restaurants in San Antonio.

Using gas chromatography–mass spectrometry, they analyzed the samples for 11 chemicals, including eight phthalates and three replacement plasticizers.

The researchers detected 10 of the 11 chemicals in fast food samples: 81% of foods contained DnBP (di-n-butyl phthalate), and 70% contained DEHP (di(2-ethylhexyl phthalate)). Meanwhile 86% of samples contained replacement plasticizer DEHT (di(2-ethylhexyl terephthalate)).

Overall, fast food samples containing meat — including chicken nuggets, chicken burritos, and hamburgers — contained higher levels of these chemicals, Dr. Edwards noted.

“We know fast food is not the most nutritious, and now we’re seeing these chemicals in it we shouldn’t be exposed to,” she said.

The results also create implications for health equity, Dr. Edwards said, as Black people in the United States report eating more fast foods than other racial and ethnic groups for many reasons, such as longstanding residential segregation.

Many advocacy groups are pushing for stronger regulations on phthalates in foods, she said, and the study can be used to fuel those efforts.

“We’re hoping our findings help people understand what they’re eating and what’s in food,” Dr. Edwards said. “If they want to reduce exposure to phthalates in fast food, they can choose foods without meat in them. But not everyone has the option of reducing fast food consumption — personal choice is important, but policy is what’s going to protect us.”

Dr. Edwards noted that the research was limited by small sample sizes gathered in one U.S. city. Limitations in extraction methods also meant the researchers were able to detect chemicals in gloves only at high concentrations.

“That being said, I do think our results are fairly generalizable,” she added, “because the way fast foods are prepared at these restaurants is fairly consistent.”

The study was funded by the Passport Foundation, Forsythia Foundation, and Marisla Foundation. Dr. Edwards has reported no relevant financial relationships.

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

During the month of September, Texans who weren’t vaccinated against COVID-19 were 20 times more likely to die from COVID-19 and related complications than those who were fully vaccinated, according to a new study from the Texas Department of State Health Services.

The data also showed that unvaccinated people were 13 times more likely to test positive for COVID-19 than people who were fully vaccinated.

“This analysis quantifies what we’ve known for months,” Jennifer Shuford, MD, the state’s chief epidemiologist, told The Dallas Morning News.

“The COVID-19 vaccines are doing an excellent job of protecting people from getting sick and from dying from COVID-19,” she said. “Vaccination remains the best way to keep yourself and the people close to you safe from this deadly disease.”

As part of the study, researchers analyzed electronic lab reports, death certificates, and state immunization records, with a particular focus on September when the contagious Delta variant surged across Texas. The research marks the state’s first statistical analysis of COVID-19 vaccinations in Texas and the effects, the newspaper reported.

The protective effect of vaccination was most noticeable among younger groups. During September, the risk of COVID-19 death was 23 times higher in unvaccinated people in their 30s and 55 times higher for unvaccinated people in their 40s.

In addition, there were fewer than 10 COVID-19 deaths in September among fully vaccinated people between ages 18-29, as compared with 339 deaths among unvaccinated people in the same age group.

Then, looking at a longer time period -- from Jan. 15 to Oct. 1 -- the researchers found that unvaccinated people were 45 times more likely to contract COVID-19 than fully vaccinated people. The protective effect of vaccination against infection was strong across all adult age groups but greatest among ages 12-17.

“All authorized COVID-19 vaccines in the United States are highly effective at protecting people from getting sick or severely ill with COVID-19, including those infected with Delta and other known variants,” the study authors wrote. “Real world data from Texas clearly shows these benefits.”

About 15.6 million people in Texas have been fully vaccinated against COVID-19 in a state of about 29 million residents, according to state data. About 66% of the population has received at least one dose, while 58% is fully vaccinated.

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

During the month of September, Texans who weren’t vaccinated against COVID-19 were 20 times more likely to die from COVID-19 and related complications than those who were fully vaccinated, according to a new study from the Texas Department of State Health Services.

The data also showed that unvaccinated people were 13 times more likely to test positive for COVID-19 than people who were fully vaccinated.

“This analysis quantifies what we’ve known for months,” Jennifer Shuford, MD, the state’s chief epidemiologist, told The Dallas Morning News.

“The COVID-19 vaccines are doing an excellent job of protecting people from getting sick and from dying from COVID-19,” she said. “Vaccination remains the best way to keep yourself and the people close to you safe from this deadly disease.”

As part of the study, researchers analyzed electronic lab reports, death certificates, and state immunization records, with a particular focus on September when the contagious Delta variant surged across Texas. The research marks the state’s first statistical analysis of COVID-19 vaccinations in Texas and the effects, the newspaper reported.

The protective effect of vaccination was most noticeable among younger groups. During September, the risk of COVID-19 death was 23 times higher in unvaccinated people in their 30s and 55 times higher for unvaccinated people in their 40s.

In addition, there were fewer than 10 COVID-19 deaths in September among fully vaccinated people between ages 18-29, as compared with 339 deaths among unvaccinated people in the same age group.

Then, looking at a longer time period -- from Jan. 15 to Oct. 1 -- the researchers found that unvaccinated people were 45 times more likely to contract COVID-19 than fully vaccinated people. The protective effect of vaccination against infection was strong across all adult age groups but greatest among ages 12-17.

“All authorized COVID-19 vaccines in the United States are highly effective at protecting people from getting sick or severely ill with COVID-19, including those infected with Delta and other known variants,” the study authors wrote. “Real world data from Texas clearly shows these benefits.”

About 15.6 million people in Texas have been fully vaccinated against COVID-19 in a state of about 29 million residents, according to state data. About 66% of the population has received at least one dose, while 58% is fully vaccinated.

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

During the month of September, Texans who weren’t vaccinated against COVID-19 were 20 times more likely to die from COVID-19 and related complications than those who were fully vaccinated, according to a new study from the Texas Department of State Health Services.

The data also showed that unvaccinated people were 13 times more likely to test positive for COVID-19 than people who were fully vaccinated.

“This analysis quantifies what we’ve known for months,” Jennifer Shuford, MD, the state’s chief epidemiologist, told The Dallas Morning News.

“The COVID-19 vaccines are doing an excellent job of protecting people from getting sick and from dying from COVID-19,” she said. “Vaccination remains the best way to keep yourself and the people close to you safe from this deadly disease.”

As part of the study, researchers analyzed electronic lab reports, death certificates, and state immunization records, with a particular focus on September when the contagious Delta variant surged across Texas. The research marks the state’s first statistical analysis of COVID-19 vaccinations in Texas and the effects, the newspaper reported.

The protective effect of vaccination was most noticeable among younger groups. During September, the risk of COVID-19 death was 23 times higher in unvaccinated people in their 30s and 55 times higher for unvaccinated people in their 40s.

In addition, there were fewer than 10 COVID-19 deaths in September among fully vaccinated people between ages 18-29, as compared with 339 deaths among unvaccinated people in the same age group.

Then, looking at a longer time period -- from Jan. 15 to Oct. 1 -- the researchers found that unvaccinated people were 45 times more likely to contract COVID-19 than fully vaccinated people. The protective effect of vaccination against infection was strong across all adult age groups but greatest among ages 12-17.

“All authorized COVID-19 vaccines in the United States are highly effective at protecting people from getting sick or severely ill with COVID-19, including those infected with Delta and other known variants,” the study authors wrote. “Real world data from Texas clearly shows these benefits.”

About 15.6 million people in Texas have been fully vaccinated against COVID-19 in a state of about 29 million residents, according to state data. About 66% of the population has received at least one dose, while 58% is fully vaccinated.

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

LAS VEGAS – Risankizumab (Skyrizi, AbbVie) provides early and lasting benefits for patients with Crohn’s disease, phase 3 trials indicate.

Based on these and other recent findings, the drug could be used as a first-line treatment and even displace ustekinumab (Stelara, Janssen), which itself was approved by the Food and Drug Administration for Crohn’s disease in 2016, according to David Rubin, MD, the Joseph B. Kirsner Professor of Medicine at the University of Chicago.

“The drug works fast,” Dr. Rubin said in an interview. “If you start this therapy in patients with moderate to severe Crohn’s disease, they’re likely to feel better within the first few weeks.”

Dr. Rubin presented the findings on the drug’s early onset at the annual meeting of the American College of Gastroenterology. A related trial presented at the meeting showed the drug continuing to perform well up to 52 weeks.

Advances in immunomodulation have allowed drug companies to feed multiple new therapies into the pipeline for Crohn’s disease and related conditions in recent years, giving hope to the many patients who have not been able to benefit from older classes of drugs, such as biologics.

A humanized immunoglobulin G1 (IgG1) monoclonal antibody, risankizumab blocks interleukin (IL) 23 by binding to its p19 subunit. IL-23 is a cytokine implicated in several chronic immune disorders, including Crohn’s disease and psoriasis. Researchers hope that risankizumab will prove more selective, with a better safety profile, than previous drugs in its class. The FDA approved risankizumab in April 2019 for the treatment of moderate to severe plaque psoriasis.
 

MOTIVATE and ADVANCE studies

The two induction trials for Crohn’s disease enrolled slightly different populations.

The MOTIVATE study enrolled patients who had responded inadequately or were intolerant to biologic therapy. In this trial, the investigators assigned 205 patients to 1,200 mg of risankizumab, 206 patients to 600 mg of risankizumab, and 207 patients to placebo.

The ADVANCE study enrolled patients who had responded inadequately or could not tolerate either biologic or conventional therapy. In this trial, investigators randomly assigned 372 patients to 1,200 mg of risankizumab, 373 patients to 600 mg of risankizumab, and 186 patients to placebo.

In both trials, intravenous injections were given at weeks 0, 4, and 8.

The researchers defined a Crohn’s Disease Activity Index (CDAI) clinical remission as a score less than 150. They defined a Stool Frequency and Abdominal Pain Score (SF/APS) clinical remission as a soft stool frequency of no more than 2.8, and an abdominal pain score of no more than 1 and not worse than baseline.

A CDAI clinical response was at least a 100-point decrease from baseline. The SF/APS enhanced clinical response was at least a 60% decrease in average daily stool frequency or at least a 35% decrease in average daily abdominal pain, with both not worse than baseline.

At 4 weeks, the researchers found that the percentage of patients who achieved CDAI clinical remission in both risankizumab groups of both studies was greater than in the placebo group. The difference was statistically significant (P ≤ .01 in ADVANCE and P ≤ .05 in MOTIVATE), and it continued to grow at 8 weeks and 12 weeks.

By 12 weeks in the ADVANCE trial, according to a press release from AbbVie, 45% of patients on the 600-mg dose of risankizumab and 42% on the 1,200-mg dose of risankizumab had achieved CDAI clinical remission, compared with 25% of those on placebo, which was statistically significant (P < .001). For the MOTIVATE trial, the results were significantly better for patients in the risankizumab groups than for those in the placebo group.

In both trials, the treated groups continued to improve faster than the placebo groups through 12 weeks. Improvements in SF/APS enhanced clinical response largely paralleled those for CDAI clinical remission.

“It did show very good results,” session moderator Jonathan Leighton, MD, professor of medicine and chair of the division of gastroenterology at Mayo Clinic in Phoenix, Ariz., said in an interview with Medscape Medical News. “But basically, it’s so early that we don’t have all the data.” In particular, he would have liked to see whether patients responded to the drug before week 4.
 

FORTIFY study

In FORTIFY, the maintenance trial that followed, the researchers rerandomized those patients who had responded to risankizumab into three groups. Two groups received subcutaneous injections of risankizumab, with 179 patients getting 360 mg and another 179 patients getting 180 mg. The placebo group included the remaining 184 patients.

At week 52, 40.9% of patients in the placebo group were in clinical remission, compared with 52.2% in the 360-mg group and 55.4% in the 180-mg group, which was statistically significant (P = .005 for 360 mg, and P = .003 for 180 mg.)

“It showed us that [risankizumab] could achieve deep remission, which means patients achieving remission endoscopically in combination with clinical remission,” the presenter, Marla Dubinsky, MD, professor of pediatrics and medicine in the division of pediatric gastroenterology at Icahn School of Medicine at Mount Sinai in New York, said in an interview.

Over the 52 weeks, deep remission and endoscopic remission rates increased in the 360-mg group, held steady in the 180-mg group, and decreased in the placebo group. Mean fecal calprotectin and C-reactive protein levels decreased in the risankizumab groups and increased in the placebo group.

There were more total treatment-emergent adverse events per 100 patient-years in the placebo group (339.7) than in the 360-mg group (269.3) or the 180-mg group (283.5). The same difference between groups was true of severe treatment-emergent adverse events. Serious events and events leading to discontinuation were similar in the three groups.

Dr. Leighton reports financial relationships to Olympus and Pfizer. Dr. Rubin reports financial relationships to AbbVie, AltruBio, Allergan, Arena Pharmaceuticals, Athos Therapeutics, Bellatrix, Boehringer Ingelheim, Bristol Myers Squibb, Celgene/Syneos, Connect Biopharma, GalenPharma/Atlantica, Genentech/Roche, Gilead, InDex Pharmaceuticals, Ironwood, Iterative Scopes, Janssen, Lilly, Materia Prima Farmaceutica, Pfizer, Prometheus Biosciences, Reistone, Takeda, and TECHLAB. Dr. Dubinsky reports financial relationships to all or most of the companies making drugs for inflammatory bowel disease. The studies were funded by AbbVie.

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

LAS VEGAS – Risankizumab (Skyrizi, AbbVie) provides early and lasting benefits for patients with Crohn’s disease, phase 3 trials indicate.

Based on these and other recent findings, the drug could be used as a first-line treatment and even displace ustekinumab (Stelara, Janssen), which itself was approved by the Food and Drug Administration for Crohn’s disease in 2016, according to David Rubin, MD, the Joseph B. Kirsner Professor of Medicine at the University of Chicago.

“The drug works fast,” Dr. Rubin said in an interview. “If you start this therapy in patients with moderate to severe Crohn’s disease, they’re likely to feel better within the first few weeks.”

Dr. Rubin presented the findings on the drug’s early onset at the annual meeting of the American College of Gastroenterology. A related trial presented at the meeting showed the drug continuing to perform well up to 52 weeks.

Advances in immunomodulation have allowed drug companies to feed multiple new therapies into the pipeline for Crohn’s disease and related conditions in recent years, giving hope to the many patients who have not been able to benefit from older classes of drugs, such as biologics.

A humanized immunoglobulin G1 (IgG1) monoclonal antibody, risankizumab blocks interleukin (IL) 23 by binding to its p19 subunit. IL-23 is a cytokine implicated in several chronic immune disorders, including Crohn’s disease and psoriasis. Researchers hope that risankizumab will prove more selective, with a better safety profile, than previous drugs in its class. The FDA approved risankizumab in April 2019 for the treatment of moderate to severe plaque psoriasis.
 

MOTIVATE and ADVANCE studies

The two induction trials for Crohn’s disease enrolled slightly different populations.

The MOTIVATE study enrolled patients who had responded inadequately or were intolerant to biologic therapy. In this trial, the investigators assigned 205 patients to 1,200 mg of risankizumab, 206 patients to 600 mg of risankizumab, and 207 patients to placebo.

The ADVANCE study enrolled patients who had responded inadequately or could not tolerate either biologic or conventional therapy. In this trial, investigators randomly assigned 372 patients to 1,200 mg of risankizumab, 373 patients to 600 mg of risankizumab, and 186 patients to placebo.

In both trials, intravenous injections were given at weeks 0, 4, and 8.

The researchers defined a Crohn’s Disease Activity Index (CDAI) clinical remission as a score less than 150. They defined a Stool Frequency and Abdominal Pain Score (SF/APS) clinical remission as a soft stool frequency of no more than 2.8, and an abdominal pain score of no more than 1 and not worse than baseline.

A CDAI clinical response was at least a 100-point decrease from baseline. The SF/APS enhanced clinical response was at least a 60% decrease in average daily stool frequency or at least a 35% decrease in average daily abdominal pain, with both not worse than baseline.

At 4 weeks, the researchers found that the percentage of patients who achieved CDAI clinical remission in both risankizumab groups of both studies was greater than in the placebo group. The difference was statistically significant (P ≤ .01 in ADVANCE and P ≤ .05 in MOTIVATE), and it continued to grow at 8 weeks and 12 weeks.

By 12 weeks in the ADVANCE trial, according to a press release from AbbVie, 45% of patients on the 600-mg dose of risankizumab and 42% on the 1,200-mg dose of risankizumab had achieved CDAI clinical remission, compared with 25% of those on placebo, which was statistically significant (P < .001). For the MOTIVATE trial, the results were significantly better for patients in the risankizumab groups than for those in the placebo group.

In both trials, the treated groups continued to improve faster than the placebo groups through 12 weeks. Improvements in SF/APS enhanced clinical response largely paralleled those for CDAI clinical remission.

“It did show very good results,” session moderator Jonathan Leighton, MD, professor of medicine and chair of the division of gastroenterology at Mayo Clinic in Phoenix, Ariz., said in an interview with Medscape Medical News. “But basically, it’s so early that we don’t have all the data.” In particular, he would have liked to see whether patients responded to the drug before week 4.
 

FORTIFY study

In FORTIFY, the maintenance trial that followed, the researchers rerandomized those patients who had responded to risankizumab into three groups. Two groups received subcutaneous injections of risankizumab, with 179 patients getting 360 mg and another 179 patients getting 180 mg. The placebo group included the remaining 184 patients.

At week 52, 40.9% of patients in the placebo group were in clinical remission, compared with 52.2% in the 360-mg group and 55.4% in the 180-mg group, which was statistically significant (P = .005 for 360 mg, and P = .003 for 180 mg.)

“It showed us that [risankizumab] could achieve deep remission, which means patients achieving remission endoscopically in combination with clinical remission,” the presenter, Marla Dubinsky, MD, professor of pediatrics and medicine in the division of pediatric gastroenterology at Icahn School of Medicine at Mount Sinai in New York, said in an interview.

Over the 52 weeks, deep remission and endoscopic remission rates increased in the 360-mg group, held steady in the 180-mg group, and decreased in the placebo group. Mean fecal calprotectin and C-reactive protein levels decreased in the risankizumab groups and increased in the placebo group.

There were more total treatment-emergent adverse events per 100 patient-years in the placebo group (339.7) than in the 360-mg group (269.3) or the 180-mg group (283.5). The same difference between groups was true of severe treatment-emergent adverse events. Serious events and events leading to discontinuation were similar in the three groups.

Dr. Leighton reports financial relationships to Olympus and Pfizer. Dr. Rubin reports financial relationships to AbbVie, AltruBio, Allergan, Arena Pharmaceuticals, Athos Therapeutics, Bellatrix, Boehringer Ingelheim, Bristol Myers Squibb, Celgene/Syneos, Connect Biopharma, GalenPharma/Atlantica, Genentech/Roche, Gilead, InDex Pharmaceuticals, Ironwood, Iterative Scopes, Janssen, Lilly, Materia Prima Farmaceutica, Pfizer, Prometheus Biosciences, Reistone, Takeda, and TECHLAB. Dr. Dubinsky reports financial relationships to all or most of the companies making drugs for inflammatory bowel disease. The studies were funded by AbbVie.

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

LAS VEGAS – Risankizumab (Skyrizi, AbbVie) provides early and lasting benefits for patients with Crohn’s disease, phase 3 trials indicate.

Based on these and other recent findings, the drug could be used as a first-line treatment and even displace ustekinumab (Stelara, Janssen), which itself was approved by the Food and Drug Administration for Crohn’s disease in 2016, according to David Rubin, MD, the Joseph B. Kirsner Professor of Medicine at the University of Chicago.

“The drug works fast,” Dr. Rubin said in an interview. “If you start this therapy in patients with moderate to severe Crohn’s disease, they’re likely to feel better within the first few weeks.”

Dr. Rubin presented the findings on the drug’s early onset at the annual meeting of the American College of Gastroenterology. A related trial presented at the meeting showed the drug continuing to perform well up to 52 weeks.

Advances in immunomodulation have allowed drug companies to feed multiple new therapies into the pipeline for Crohn’s disease and related conditions in recent years, giving hope to the many patients who have not been able to benefit from older classes of drugs, such as biologics.

A humanized immunoglobulin G1 (IgG1) monoclonal antibody, risankizumab blocks interleukin (IL) 23 by binding to its p19 subunit. IL-23 is a cytokine implicated in several chronic immune disorders, including Crohn’s disease and psoriasis. Researchers hope that risankizumab will prove more selective, with a better safety profile, than previous drugs in its class. The FDA approved risankizumab in April 2019 for the treatment of moderate to severe plaque psoriasis.
 

MOTIVATE and ADVANCE studies

The two induction trials for Crohn’s disease enrolled slightly different populations.

The MOTIVATE study enrolled patients who had responded inadequately or were intolerant to biologic therapy. In this trial, the investigators assigned 205 patients to 1,200 mg of risankizumab, 206 patients to 600 mg of risankizumab, and 207 patients to placebo.

The ADVANCE study enrolled patients who had responded inadequately or could not tolerate either biologic or conventional therapy. In this trial, investigators randomly assigned 372 patients to 1,200 mg of risankizumab, 373 patients to 600 mg of risankizumab, and 186 patients to placebo.

In both trials, intravenous injections were given at weeks 0, 4, and 8.

The researchers defined a Crohn’s Disease Activity Index (CDAI) clinical remission as a score less than 150. They defined a Stool Frequency and Abdominal Pain Score (SF/APS) clinical remission as a soft stool frequency of no more than 2.8, and an abdominal pain score of no more than 1 and not worse than baseline.

A CDAI clinical response was at least a 100-point decrease from baseline. The SF/APS enhanced clinical response was at least a 60% decrease in average daily stool frequency or at least a 35% decrease in average daily abdominal pain, with both not worse than baseline.

At 4 weeks, the researchers found that the percentage of patients who achieved CDAI clinical remission in both risankizumab groups of both studies was greater than in the placebo group. The difference was statistically significant (P ≤ .01 in ADVANCE and P ≤ .05 in MOTIVATE), and it continued to grow at 8 weeks and 12 weeks.

By 12 weeks in the ADVANCE trial, according to a press release from AbbVie, 45% of patients on the 600-mg dose of risankizumab and 42% on the 1,200-mg dose of risankizumab had achieved CDAI clinical remission, compared with 25% of those on placebo, which was statistically significant (P < .001). For the MOTIVATE trial, the results were significantly better for patients in the risankizumab groups than for those in the placebo group.

In both trials, the treated groups continued to improve faster than the placebo groups through 12 weeks. Improvements in SF/APS enhanced clinical response largely paralleled those for CDAI clinical remission.

“It did show very good results,” session moderator Jonathan Leighton, MD, professor of medicine and chair of the division of gastroenterology at Mayo Clinic in Phoenix, Ariz., said in an interview with Medscape Medical News. “But basically, it’s so early that we don’t have all the data.” In particular, he would have liked to see whether patients responded to the drug before week 4.
 

FORTIFY study

In FORTIFY, the maintenance trial that followed, the researchers rerandomized those patients who had responded to risankizumab into three groups. Two groups received subcutaneous injections of risankizumab, with 179 patients getting 360 mg and another 179 patients getting 180 mg. The placebo group included the remaining 184 patients.

At week 52, 40.9% of patients in the placebo group were in clinical remission, compared with 52.2% in the 360-mg group and 55.4% in the 180-mg group, which was statistically significant (P = .005 for 360 mg, and P = .003 for 180 mg.)

“It showed us that [risankizumab] could achieve deep remission, which means patients achieving remission endoscopically in combination with clinical remission,” the presenter, Marla Dubinsky, MD, professor of pediatrics and medicine in the division of pediatric gastroenterology at Icahn School of Medicine at Mount Sinai in New York, said in an interview.

Over the 52 weeks, deep remission and endoscopic remission rates increased in the 360-mg group, held steady in the 180-mg group, and decreased in the placebo group. Mean fecal calprotectin and C-reactive protein levels decreased in the risankizumab groups and increased in the placebo group.

There were more total treatment-emergent adverse events per 100 patient-years in the placebo group (339.7) than in the 360-mg group (269.3) or the 180-mg group (283.5). The same difference between groups was true of severe treatment-emergent adverse events. Serious events and events leading to discontinuation were similar in the three groups.

Dr. Leighton reports financial relationships to Olympus and Pfizer. Dr. Rubin reports financial relationships to AbbVie, AltruBio, Allergan, Arena Pharmaceuticals, Athos Therapeutics, Bellatrix, Boehringer Ingelheim, Bristol Myers Squibb, Celgene/Syneos, Connect Biopharma, GalenPharma/Atlantica, Genentech/Roche, Gilead, InDex Pharmaceuticals, Ironwood, Iterative Scopes, Janssen, Lilly, Materia Prima Farmaceutica, Pfizer, Prometheus Biosciences, Reistone, Takeda, and TECHLAB. Dr. Dubinsky reports financial relationships to all or most of the companies making drugs for inflammatory bowel disease. The studies were funded by AbbVie.

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

The glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide (Saxenda, Novo Nordisk) was safe and effective for treating weight regain after Roux-en-Y gastric bypass (RYGB), in a randomized controlled trial.

That is, 132 patients who had lost at least 25% of their initial weight after RYGB and then gained at least 10% back were randomized 2:1 to receive liraglutide plus frequent lifestyle advice from a registered dietitian or lifestyle advice alone.

After a year, 69%, 48%, and 24% of patients who had received liraglutide lost at least 5%, 10%, and 15% of their study entry weight, respectively. In contrast, only 5% of patients in the control group lost at least 5% of their weight and none lost at least 10% of their weight.

“Liraglutide 3.0 mg/day, with lifestyle modification, was significantly more effective than placebo in treating weight regain after RYGB without increased risk of serious adverse events,” Holly F. Lofton, MD, summarized this week in an oral session at ObesityWeek®, the annual meeting of The Obesity Society.

Dr. Lofton, a clinical associate professor of surgery and medicine, and director, weight management program, NYU, Langone Health, explained to this news organization that she initiated the study after attending a “packed” session about post bariatric surgery weight regain at a prior American Society of Metabolic and Bariatric Surgery conference.

“The lecturers recommended conservative measures (such as reiterating the diet recommendations, exercise, [and] counseling), and revisional surgeries,” she said in an email, but at the time “there was no literature that provided direction on which pharmacotherapies are best for this population.”

It was known that decreases in endogenous GLP-1 levels coincide with weight regain, and liraglutide (Saxenda) was the only GLP-1 agonist approved for chronic weight management at the time, so she devised the current study protocol.

The findings are especially helpful for patients who are not candidates for bariatric surgery revisions, she noted. Further research is needed to investigate the effect of newer GLP-1 agonists, such as semaglutide (Wegovy), on weight regain following different types of bariatric surgery.

Asked to comment, Wendy C. King, PhD, who was not involved with this research, said that more than two-thirds of patients treated with 3 mg/day subcutaneous liraglutide injections in the current study lost at least 5% of their initial weight a year later, and 20% of them attained a weight as low as, or lower than, their lowest weight after bariatric surgery (nadir weight).

“The fact that both groups received lifestyle counseling from registered dietitians for just over a year, but only patients in the liraglutide group lost weight, on average, speaks to the difficulty of losing weight following weight regain post–bariatric surgery,” added Dr. King, an associate professor of epidemiology at the University of Pittsburgh, Pennsylvania.

This study “provides data that may help clinicians and patients understand the potential effect of adding liraglutide 3.0 mg/day to their weight loss efforts,” she told this news organization in an email.

However, “given that 42% of those on liraglutide reported gastrointestinal-related side effects, patients should also be counseled on this potential outcome and given suggestions for how to minimize such side effects,” Dr. King suggested.
 

Weight regain common, repeat surgery entails risk

Weight regain is common even years after bariatric surgery. Repeat surgery entails some risk, and lifestyle approaches alone are rarely successful in reversing weight regain, Dr. Lofton told the audience.

The researchers enrolled 132 adults who had a mean weight of 134 kg (295 pounds) when they underwent RYGB, and who lost at least 25% of their initial weight (mean weight loss of 38%) after the surgery, but who also regained at least 10% of their initial weight.

At enrollment of the current study (baseline), the patients had had RYGB 18 months to 10 years earlier (mean 5.7 years earlier) and now had a mean weight of 99 kg (218 pounds) and a mean BMI of 35.6 kg/m². None of the patients had diabetes.  

The patients were randomized to receive liraglutide (n = 89, 84% women) or placebo (n = 43, 88% women) for 56 weeks.

They were a mean age of 48 years, and about 59% were White and 25% were Black.

All patients had clinic visits every 3 months where they received lifestyle counseling from a registered dietitian.

At 12 months, patients in the liraglutide group had lost a mean of 8.8% of their baseline weight, whereas those in the placebo group had gained a mean of 1.48% of their baseline weight.

There were no significant between-group differences in cardiometabolic variables.

None of the patients in the control group attained a weight that was as low as their nadir weight after RYGB.

The rates of nausea (25%), constipation (16%), and abdominal pain (10%) in the liraglutide group were higher than in the placebo group (7%, 14%, and 5%, respectively) but similar to rates of gastrointestinal side effects in other trials of this agent.

Dr. Lofton has disclosed receiving consulting fees and being on a speaker bureau for Novo Nordisk and receiving research funds from Boehringer Ingelheim, Eli Lilly, and Novo Nordisk. Dr. King has reported no relevant financial relationships.

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

The glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide (Saxenda, Novo Nordisk) was safe and effective for treating weight regain after Roux-en-Y gastric bypass (RYGB), in a randomized controlled trial.

That is, 132 patients who had lost at least 25% of their initial weight after RYGB and then gained at least 10% back were randomized 2:1 to receive liraglutide plus frequent lifestyle advice from a registered dietitian or lifestyle advice alone.

After a year, 69%, 48%, and 24% of patients who had received liraglutide lost at least 5%, 10%, and 15% of their study entry weight, respectively. In contrast, only 5% of patients in the control group lost at least 5% of their weight and none lost at least 10% of their weight.

“Liraglutide 3.0 mg/day, with lifestyle modification, was significantly more effective than placebo in treating weight regain after RYGB without increased risk of serious adverse events,” Holly F. Lofton, MD, summarized this week in an oral session at ObesityWeek®, the annual meeting of The Obesity Society.

Dr. Lofton, a clinical associate professor of surgery and medicine, and director, weight management program, NYU, Langone Health, explained to this news organization that she initiated the study after attending a “packed” session about post bariatric surgery weight regain at a prior American Society of Metabolic and Bariatric Surgery conference.

“The lecturers recommended conservative measures (such as reiterating the diet recommendations, exercise, [and] counseling), and revisional surgeries,” she said in an email, but at the time “there was no literature that provided direction on which pharmacotherapies are best for this population.”

It was known that decreases in endogenous GLP-1 levels coincide with weight regain, and liraglutide (Saxenda) was the only GLP-1 agonist approved for chronic weight management at the time, so she devised the current study protocol.

The findings are especially helpful for patients who are not candidates for bariatric surgery revisions, she noted. Further research is needed to investigate the effect of newer GLP-1 agonists, such as semaglutide (Wegovy), on weight regain following different types of bariatric surgery.

Asked to comment, Wendy C. King, PhD, who was not involved with this research, said that more than two-thirds of patients treated with 3 mg/day subcutaneous liraglutide injections in the current study lost at least 5% of their initial weight a year later, and 20% of them attained a weight as low as, or lower than, their lowest weight after bariatric surgery (nadir weight).

“The fact that both groups received lifestyle counseling from registered dietitians for just over a year, but only patients in the liraglutide group lost weight, on average, speaks to the difficulty of losing weight following weight regain post–bariatric surgery,” added Dr. King, an associate professor of epidemiology at the University of Pittsburgh, Pennsylvania.

This study “provides data that may help clinicians and patients understand the potential effect of adding liraglutide 3.0 mg/day to their weight loss efforts,” she told this news organization in an email.

However, “given that 42% of those on liraglutide reported gastrointestinal-related side effects, patients should also be counseled on this potential outcome and given suggestions for how to minimize such side effects,” Dr. King suggested.
 

Weight regain common, repeat surgery entails risk

Weight regain is common even years after bariatric surgery. Repeat surgery entails some risk, and lifestyle approaches alone are rarely successful in reversing weight regain, Dr. Lofton told the audience.

The researchers enrolled 132 adults who had a mean weight of 134 kg (295 pounds) when they underwent RYGB, and who lost at least 25% of their initial weight (mean weight loss of 38%) after the surgery, but who also regained at least 10% of their initial weight.

At enrollment of the current study (baseline), the patients had had RYGB 18 months to 10 years earlier (mean 5.7 years earlier) and now had a mean weight of 99 kg (218 pounds) and a mean BMI of 35.6 kg/m². None of the patients had diabetes.  

The patients were randomized to receive liraglutide (n = 89, 84% women) or placebo (n = 43, 88% women) for 56 weeks.

They were a mean age of 48 years, and about 59% were White and 25% were Black.

All patients had clinic visits every 3 months where they received lifestyle counseling from a registered dietitian.

At 12 months, patients in the liraglutide group had lost a mean of 8.8% of their baseline weight, whereas those in the placebo group had gained a mean of 1.48% of their baseline weight.

There were no significant between-group differences in cardiometabolic variables.

None of the patients in the control group attained a weight that was as low as their nadir weight after RYGB.

The rates of nausea (25%), constipation (16%), and abdominal pain (10%) in the liraglutide group were higher than in the placebo group (7%, 14%, and 5%, respectively) but similar to rates of gastrointestinal side effects in other trials of this agent.

Dr. Lofton has disclosed receiving consulting fees and being on a speaker bureau for Novo Nordisk and receiving research funds from Boehringer Ingelheim, Eli Lilly, and Novo Nordisk. Dr. King has reported no relevant financial relationships.

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

The glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide (Saxenda, Novo Nordisk) was safe and effective for treating weight regain after Roux-en-Y gastric bypass (RYGB), in a randomized controlled trial.

That is, 132 patients who had lost at least 25% of their initial weight after RYGB and then gained at least 10% back were randomized 2:1 to receive liraglutide plus frequent lifestyle advice from a registered dietitian or lifestyle advice alone.

After a year, 69%, 48%, and 24% of patients who had received liraglutide lost at least 5%, 10%, and 15% of their study entry weight, respectively. In contrast, only 5% of patients in the control group lost at least 5% of their weight and none lost at least 10% of their weight.

“Liraglutide 3.0 mg/day, with lifestyle modification, was significantly more effective than placebo in treating weight regain after RYGB without increased risk of serious adverse events,” Holly F. Lofton, MD, summarized this week in an oral session at ObesityWeek®, the annual meeting of The Obesity Society.

Dr. Lofton, a clinical associate professor of surgery and medicine, and director, weight management program, NYU, Langone Health, explained to this news organization that she initiated the study after attending a “packed” session about post bariatric surgery weight regain at a prior American Society of Metabolic and Bariatric Surgery conference.

“The lecturers recommended conservative measures (such as reiterating the diet recommendations, exercise, [and] counseling), and revisional surgeries,” she said in an email, but at the time “there was no literature that provided direction on which pharmacotherapies are best for this population.”

It was known that decreases in endogenous GLP-1 levels coincide with weight regain, and liraglutide (Saxenda) was the only GLP-1 agonist approved for chronic weight management at the time, so she devised the current study protocol.

The findings are especially helpful for patients who are not candidates for bariatric surgery revisions, she noted. Further research is needed to investigate the effect of newer GLP-1 agonists, such as semaglutide (Wegovy), on weight regain following different types of bariatric surgery.

Asked to comment, Wendy C. King, PhD, who was not involved with this research, said that more than two-thirds of patients treated with 3 mg/day subcutaneous liraglutide injections in the current study lost at least 5% of their initial weight a year later, and 20% of them attained a weight as low as, or lower than, their lowest weight after bariatric surgery (nadir weight).

“The fact that both groups received lifestyle counseling from registered dietitians for just over a year, but only patients in the liraglutide group lost weight, on average, speaks to the difficulty of losing weight following weight regain post–bariatric surgery,” added Dr. King, an associate professor of epidemiology at the University of Pittsburgh, Pennsylvania.

This study “provides data that may help clinicians and patients understand the potential effect of adding liraglutide 3.0 mg/day to their weight loss efforts,” she told this news organization in an email.

However, “given that 42% of those on liraglutide reported gastrointestinal-related side effects, patients should also be counseled on this potential outcome and given suggestions for how to minimize such side effects,” Dr. King suggested.
 

Weight regain common, repeat surgery entails risk

Weight regain is common even years after bariatric surgery. Repeat surgery entails some risk, and lifestyle approaches alone are rarely successful in reversing weight regain, Dr. Lofton told the audience.

The researchers enrolled 132 adults who had a mean weight of 134 kg (295 pounds) when they underwent RYGB, and who lost at least 25% of their initial weight (mean weight loss of 38%) after the surgery, but who also regained at least 10% of their initial weight.

At enrollment of the current study (baseline), the patients had had RYGB 18 months to 10 years earlier (mean 5.7 years earlier) and now had a mean weight of 99 kg (218 pounds) and a mean BMI of 35.6 kg/m². None of the patients had diabetes.  

The patients were randomized to receive liraglutide (n = 89, 84% women) or placebo (n = 43, 88% women) for 56 weeks.

They were a mean age of 48 years, and about 59% were White and 25% were Black.

All patients had clinic visits every 3 months where they received lifestyle counseling from a registered dietitian.

At 12 months, patients in the liraglutide group had lost a mean of 8.8% of their baseline weight, whereas those in the placebo group had gained a mean of 1.48% of their baseline weight.

There were no significant between-group differences in cardiometabolic variables.

None of the patients in the control group attained a weight that was as low as their nadir weight after RYGB.

The rates of nausea (25%), constipation (16%), and abdominal pain (10%) in the liraglutide group were higher than in the placebo group (7%, 14%, and 5%, respectively) but similar to rates of gastrointestinal side effects in other trials of this agent.

Dr. Lofton has disclosed receiving consulting fees and being on a speaker bureau for Novo Nordisk and receiving research funds from Boehringer Ingelheim, Eli Lilly, and Novo Nordisk. Dr. King has reported no relevant financial relationships.

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

The use of statins by patients with rheumatoid arthritis appears to provide an overall net benefit on cardiovascular disease outcomes that outweighs the risk of type 2 diabetes mellitus (T2DM) seen with the drugs in the general population, according to evidence from a cohort study of more than 16,000 people in the United Kingdom that was presented at the virtual annual meeting of the American College of Rheumatology.

“Our study emphasizes that RA patients should be assessed for statin initiation to improve CVD risk,” lead study author Gulsen Ozen, MD, a third-year resident at the University of Nebraska, Omaha, said in an interview. Because the risk of T2DM with statin use is no worse in patients with RA than in the general population, statin initiation “is actually a great opportunity to address the risk factors for T2DM such as activity and exercise, obesity and weight loss, and [use of glucocorticoids], which have other important health effects,” she said.

“Also, importantly, even if [patients] develop T2DM, statins still work on CVD and mortality outcomes as in patients without diabetes,” Dr. Ozen added. “Given all, the benefits of statins way outweigh the hazards.”

Dr. Ozen said this was the first large cohort study to evaluate CVD mortality and T2DM risks with statins in patients with RA, a claim with which rheumatologist Elena Myasoedova, MD, PhD, of the Mayo Clinic in Rochester, Minn., concurred.

Dr. Myasoedova, professor of rheumatology and epidemiology at Mayo, said in an interview that the study was “methodologically rigorous” using time-conditional propensity score (TCPS) matching and a prevalent new-user design, “thus addressing the immortal time bias” found in the design of studies in which patients enter a cohort but do not start a treatment before developing the outcome of interest and are assigned to the untreated group or when the period of delay from when patients enter the cohort to when they are treated is excluded from the analysis. An earlier study from the same authors did not use TCPS matching, she said.

“The study findings suggest that patients with RA can benefit from statin use in terms of CVD outcomes and mortality but physicians should use vigilance regarding increased T2DM risk and discuss this possibility with patients,” Dr. Myasoedova said. “Identifying patients who are at higher risk of developing T2DM after statin initiation would be important to personalize the approach to statin therapy.”
 

Study details

The study accessed records from the U.K. Clinical Practice Research Datalink and linked Hospital Episode Statistics and Office of National Statistics databases. It analyzed adult patients with RA who were diagnosed during 1989-2018 in two cohorts: One for CVD and all-cause mortality, consisting of 1,768 statin initiators and 3,528 TCPS-matched nonusers; and a T2DM cohort with 3,608 statin initiators and 7,208 TCPS-matched nonusers.

In the entire cohort, statin use was associated with a 32% reduction in CV events (composite endpoint of the nonfatal or fatal MI, stroke, hospitalized heart failure, or CVD mortality), a 54% reduction in all-cause mortality, and a 33% increase in risk for T2DM, Dr. Ozen said. Results were similar in both sexes, although CV event reduction with statins in men did not reach statistical significance, likely because of a smaller sample size, she said.

Patients with and without a history of CVD had a similar reduction in CV events and all-cause mortality, and risk for T2DM increased with statins, but the latter reached statistical significance only in patients without a history of CVD, Dr. Ozen said.

Patients with RA who are at risk for T2DM and who are taking statins require blood glucose monitoring, which is typically done in patients with RA on disease-modifying antirheumatic drugs, and hemoglobin A1c testing when glucose levels are impaired, she said. “Any concerns for T2DM would be also communicated by the primary care providers of the patients to initiate further assessment and management,” she said.

But Dr. Ozen noted that confusion exists among primary care physicians and rheumatologists about who’s responsible for prescribing statins in these patients. “I would like to remind you that instead of assigning this role to a certain specialty, just good communication could improve this care gap of statin underutilization in RA,” she said. “Also, for rheumatologists, given that all-cause mortality reduction with statins was as high as CV event reduction, statins may be reducing other causes of mortality through improving disease activity.”

Bristol-Myers Squibb provided funding for the study. Dr. Ozen and Dr. Myasoedova have no relevant disclosures.

The use of statins by patients with rheumatoid arthritis appears to provide an overall net benefit on cardiovascular disease outcomes that outweighs the risk of type 2 diabetes mellitus (T2DM) seen with the drugs in the general population, according to evidence from a cohort study of more than 16,000 people in the United Kingdom that was presented at the virtual annual meeting of the American College of Rheumatology.

“Our study emphasizes that RA patients should be assessed for statin initiation to improve CVD risk,” lead study author Gulsen Ozen, MD, a third-year resident at the University of Nebraska, Omaha, said in an interview. Because the risk of T2DM with statin use is no worse in patients with RA than in the general population, statin initiation “is actually a great opportunity to address the risk factors for T2DM such as activity and exercise, obesity and weight loss, and [use of glucocorticoids], which have other important health effects,” she said.

“Also, importantly, even if [patients] develop T2DM, statins still work on CVD and mortality outcomes as in patients without diabetes,” Dr. Ozen added. “Given all, the benefits of statins way outweigh the hazards.”

Dr. Ozen said this was the first large cohort study to evaluate CVD mortality and T2DM risks with statins in patients with RA, a claim with which rheumatologist Elena Myasoedova, MD, PhD, of the Mayo Clinic in Rochester, Minn., concurred.

Dr. Myasoedova, professor of rheumatology and epidemiology at Mayo, said in an interview that the study was “methodologically rigorous” using time-conditional propensity score (TCPS) matching and a prevalent new-user design, “thus addressing the immortal time bias” found in the design of studies in which patients enter a cohort but do not start a treatment before developing the outcome of interest and are assigned to the untreated group or when the period of delay from when patients enter the cohort to when they are treated is excluded from the analysis. An earlier study from the same authors did not use TCPS matching, she said.

“The study findings suggest that patients with RA can benefit from statin use in terms of CVD outcomes and mortality but physicians should use vigilance regarding increased T2DM risk and discuss this possibility with patients,” Dr. Myasoedova said. “Identifying patients who are at higher risk of developing T2DM after statin initiation would be important to personalize the approach to statin therapy.”
 

Study details

The study accessed records from the U.K. Clinical Practice Research Datalink and linked Hospital Episode Statistics and Office of National Statistics databases. It analyzed adult patients with RA who were diagnosed during 1989-2018 in two cohorts: One for CVD and all-cause mortality, consisting of 1,768 statin initiators and 3,528 TCPS-matched nonusers; and a T2DM cohort with 3,608 statin initiators and 7,208 TCPS-matched nonusers.

In the entire cohort, statin use was associated with a 32% reduction in CV events (composite endpoint of the nonfatal or fatal MI, stroke, hospitalized heart failure, or CVD mortality), a 54% reduction in all-cause mortality, and a 33% increase in risk for T2DM, Dr. Ozen said. Results were similar in both sexes, although CV event reduction with statins in men did not reach statistical significance, likely because of a smaller sample size, she said.

Patients with and without a history of CVD had a similar reduction in CV events and all-cause mortality, and risk for T2DM increased with statins, but the latter reached statistical significance only in patients without a history of CVD, Dr. Ozen said.

Patients with RA who are at risk for T2DM and who are taking statins require blood glucose monitoring, which is typically done in patients with RA on disease-modifying antirheumatic drugs, and hemoglobin A1c testing when glucose levels are impaired, she said. “Any concerns for T2DM would be also communicated by the primary care providers of the patients to initiate further assessment and management,” she said.

But Dr. Ozen noted that confusion exists among primary care physicians and rheumatologists about who’s responsible for prescribing statins in these patients. “I would like to remind you that instead of assigning this role to a certain specialty, just good communication could improve this care gap of statin underutilization in RA,” she said. “Also, for rheumatologists, given that all-cause mortality reduction with statins was as high as CV event reduction, statins may be reducing other causes of mortality through improving disease activity.”

Bristol-Myers Squibb provided funding for the study. Dr. Ozen and Dr. Myasoedova have no relevant disclosures.

The use of statins by patients with rheumatoid arthritis appears to provide an overall net benefit on cardiovascular disease outcomes that outweighs the risk of type 2 diabetes mellitus (T2DM) seen with the drugs in the general population, according to evidence from a cohort study of more than 16,000 people in the United Kingdom that was presented at the virtual annual meeting of the American College of Rheumatology.