Bianca Nogrady

Long-term pioglitazone is not only safe for patients with nonalcoholic steatohepatitis (NASH) and prediabetes or type 2 diabetes but is associated with significant improvements in fatty liver disease outcomes, compared with placebo, research suggests.

Investigators randomized 101 individuals with biopsy-proven NASH and either prediabetes or type 2 diabetes to 18 months of 45 mg/day of pioglitazone or placebo, followed by an 18 month open-label phase of pioglitazone, in addition to a hypocaloric diet, according to a paper published online June 20 in the Annals of Internal Medicine.

©pixologicstudio/thinkstockphotos.com

Among patients randomized to pioglitazone, 58% achieved at least a two-point reduction in their NASH activity score, without a worsening of fibrosis, compared with only 17% of the placebo group (P less than .001).

The pioglitazone group also showed a significantly greater likelihood that their NASH would resolve, with 51% of the treatment group achieving resolution, compared with 19% of the placebo group (P less than .001).

Pioglitazone treatment was also associated with significantly greater improvements in steatosis, inflammation, and ballooning necrosis, as well as mean histologic scores and fibrosis scores (Ann Intern Med. 2016 Jun 20. doi: 10.7326/M15-1774).

The study also showed that only 12% of the pioglitazone group showed progression of any fibrosis, compared with 28% of the placebo group (P = .039), while pioglitazone was associated with significant 2.5 kg weight gain over placebo.

“Because thiazolidinediones target insulin resistance and adipose tissue dysfunction or inflammation that promotes hepatic ‘lipotoxicity’ in NASH (which is also a prominent feature of T2DM), they may be more helpful for treating steatohepatitis in this population,” wrote Dr. Kenneth Cusi, from the division of endocrinology at the University of Florida, Gainesville, and his coauthors.

However, the authors noted that there have been relatively few studies of pioglitazone and its effects on steatohepatitis in individuals with prediabetes or type 2 diabetes.

“This study also has implications for patients with prediabetes and NASH (about half of our participants) because hepatic steatosis is a risk factor for T2DM, even in nonobese patients,” the authors wrote. They suggested that future studies could explore whether the reversal of hepatic steatosis or nonalcoholic steatohepatitis in patients with prediabetes may help to halt the development of type 2 diabetes.

The study was supported by the Burroughs Wellcome Fund and the American Diabetes Association. One author reported nonfinancial support from Takeda Pharmaceuticals in the form of study medication and placebo, and grants and consultancies from pharmaceutical companies outside the submitted work. No other conflicts of interest were declared.

Long-term pioglitazone is not only safe for patients with nonalcoholic steatohepatitis (NASH) and prediabetes or type 2 diabetes but is associated with significant improvements in fatty liver disease outcomes, compared with placebo, research suggests.

Investigators randomized 101 individuals with biopsy-proven NASH and either prediabetes or type 2 diabetes to 18 months of 45 mg/day of pioglitazone or placebo, followed by an 18 month open-label phase of pioglitazone, in addition to a hypocaloric diet, according to a paper published online June 20 in the Annals of Internal Medicine.

©pixologicstudio/thinkstockphotos.com

Among patients randomized to pioglitazone, 58% achieved at least a two-point reduction in their NASH activity score, without a worsening of fibrosis, compared with only 17% of the placebo group (P less than .001).

The pioglitazone group also showed a significantly greater likelihood that their NASH would resolve, with 51% of the treatment group achieving resolution, compared with 19% of the placebo group (P less than .001).

Pioglitazone treatment was also associated with significantly greater improvements in steatosis, inflammation, and ballooning necrosis, as well as mean histologic scores and fibrosis scores (Ann Intern Med. 2016 Jun 20. doi: 10.7326/M15-1774).

The study also showed that only 12% of the pioglitazone group showed progression of any fibrosis, compared with 28% of the placebo group (P = .039), while pioglitazone was associated with significant 2.5 kg weight gain over placebo.

“Because thiazolidinediones target insulin resistance and adipose tissue dysfunction or inflammation that promotes hepatic ‘lipotoxicity’ in NASH (which is also a prominent feature of T2DM), they may be more helpful for treating steatohepatitis in this population,” wrote Dr. Kenneth Cusi, from the division of endocrinology at the University of Florida, Gainesville, and his coauthors.

However, the authors noted that there have been relatively few studies of pioglitazone and its effects on steatohepatitis in individuals with prediabetes or type 2 diabetes.

“This study also has implications for patients with prediabetes and NASH (about half of our participants) because hepatic steatosis is a risk factor for T2DM, even in nonobese patients,” the authors wrote. They suggested that future studies could explore whether the reversal of hepatic steatosis or nonalcoholic steatohepatitis in patients with prediabetes may help to halt the development of type 2 diabetes.

The study was supported by the Burroughs Wellcome Fund and the American Diabetes Association. One author reported nonfinancial support from Takeda Pharmaceuticals in the form of study medication and placebo, and grants and consultancies from pharmaceutical companies outside the submitted work. No other conflicts of interest were declared.

Long-term pioglitazone is not only safe for patients with nonalcoholic steatohepatitis (NASH) and prediabetes or type 2 diabetes but is associated with significant improvements in fatty liver disease outcomes, compared with placebo, research suggests.

Investigators randomized 101 individuals with biopsy-proven NASH and either prediabetes or type 2 diabetes to 18 months of 45 mg/day of pioglitazone or placebo, followed by an 18 month open-label phase of pioglitazone, in addition to a hypocaloric diet, according to a paper published online June 20 in the Annals of Internal Medicine.

©pixologicstudio/thinkstockphotos.com

Among patients randomized to pioglitazone, 58% achieved at least a two-point reduction in their NASH activity score, without a worsening of fibrosis, compared with only 17% of the placebo group (P less than .001).

The pioglitazone group also showed a significantly greater likelihood that their NASH would resolve, with 51% of the treatment group achieving resolution, compared with 19% of the placebo group (P less than .001).

Pioglitazone treatment was also associated with significantly greater improvements in steatosis, inflammation, and ballooning necrosis, as well as mean histologic scores and fibrosis scores (Ann Intern Med. 2016 Jun 20. doi: 10.7326/M15-1774).

The study also showed that only 12% of the pioglitazone group showed progression of any fibrosis, compared with 28% of the placebo group (P = .039), while pioglitazone was associated with significant 2.5 kg weight gain over placebo.

“Because thiazolidinediones target insulin resistance and adipose tissue dysfunction or inflammation that promotes hepatic ‘lipotoxicity’ in NASH (which is also a prominent feature of T2DM), they may be more helpful for treating steatohepatitis in this population,” wrote Dr. Kenneth Cusi, from the division of endocrinology at the University of Florida, Gainesville, and his coauthors.

However, the authors noted that there have been relatively few studies of pioglitazone and its effects on steatohepatitis in individuals with prediabetes or type 2 diabetes.

“This study also has implications for patients with prediabetes and NASH (about half of our participants) because hepatic steatosis is a risk factor for T2DM, even in nonobese patients,” the authors wrote. They suggested that future studies could explore whether the reversal of hepatic steatosis or nonalcoholic steatohepatitis in patients with prediabetes may help to halt the development of type 2 diabetes.

The study was supported by the Burroughs Wellcome Fund and the American Diabetes Association. One author reported nonfinancial support from Takeda Pharmaceuticals in the form of study medication and placebo, and grants and consultancies from pharmaceutical companies outside the submitted work. No other conflicts of interest were declared.

Researchers have identified a “sweet spot” target for reducing low-density lipoprotein cholesterol levels with statin therapy that is associated with the lowest risk of adverse cardiac outcomes.

A study published online June 20 in JAMA Internal Medicine analyzed data from an Israeli health care organization between 2009-2013 and identified 31,619 patients with ischemic heart disease, aged 30-84 years, who were being treated with statins and were at least 80% adherent to the medication regime.

Louise Koenig/Frontline Medical News

The analysis showed individuals who achieved a “moderate” LDL-C level – between 70.1-100.0 mg/dL – after 1 year of statin treatment had an 11% lower incidence of major adverse cardiac events, compared with those with a “high” LDL-C level – between 100.1-130.0 mg/dL (95% confidence interval, 0.84-0.94; P less than .001).

However researchers observed no significant difference in the risk of adverse cardiac events between the moderate group and those who achieved a “low” LDL-C equal to or less than 70.0mg/dL (hazard ratio, 1.02; 95% CI, 0.97-1.07; P = .54).

In a further analysis that included 54,884 individuals who were at least 50% adherent to their statin therapy, there was a slightly increased risk of major cardiac events in patients who achieved a low LDL-C, compared with those in the moderate LDL-C group, and a significant 13% reduction in risk in the moderate LDL-C group, compared with the high LDL-C group.

“Whereas this may reflect clinical risk of low levels of LDL-C, these results further support the main findings of this study that achieving a level below 70 mg/dL is not beneficial for all patients,” wrote Dr. Morton Leibowitz, from the Clalit Research Institute, Tel Aviv, and his coauthors.

Adjustment for age did not significantly alter the interaction between LDL-C levels and the risk of adverse cardiac events (JAMA Intern Med. 2016 Jun 20. doi: 10.1001/jamainternmed.2016.2751).

“The question of the association between achieved LDL-C levels and major adverse cardiac events for secondary prevention has become highly relevant, particularly in the real-world context of patients excluded from [randomized, controlled trials],” the authors wrote, suggesting that their data only partially support recent claims that lower LDL-C is better for cardiac outcomes.

“Our findings of significantly lower risk of MACEs associated with achieved LDL-C level of less than 100.0 mg/dL but not with achieved LDL-C of less than 70.0 mg/dL suggest a target for long-term statin treatment.”

The study was funded by the Clalit Research Institute. No conflicts of interest were reported.

Researchers have identified a “sweet spot” target for reducing low-density lipoprotein cholesterol levels with statin therapy that is associated with the lowest risk of adverse cardiac outcomes.

A study published online June 20 in JAMA Internal Medicine analyzed data from an Israeli health care organization between 2009-2013 and identified 31,619 patients with ischemic heart disease, aged 30-84 years, who were being treated with statins and were at least 80% adherent to the medication regime.

Louise Koenig/Frontline Medical News

The analysis showed individuals who achieved a “moderate” LDL-C level – between 70.1-100.0 mg/dL – after 1 year of statin treatment had an 11% lower incidence of major adverse cardiac events, compared with those with a “high” LDL-C level – between 100.1-130.0 mg/dL (95% confidence interval, 0.84-0.94; P less than .001).

However researchers observed no significant difference in the risk of adverse cardiac events between the moderate group and those who achieved a “low” LDL-C equal to or less than 70.0mg/dL (hazard ratio, 1.02; 95% CI, 0.97-1.07; P = .54).

In a further analysis that included 54,884 individuals who were at least 50% adherent to their statin therapy, there was a slightly increased risk of major cardiac events in patients who achieved a low LDL-C, compared with those in the moderate LDL-C group, and a significant 13% reduction in risk in the moderate LDL-C group, compared with the high LDL-C group.

“Whereas this may reflect clinical risk of low levels of LDL-C, these results further support the main findings of this study that achieving a level below 70 mg/dL is not beneficial for all patients,” wrote Dr. Morton Leibowitz, from the Clalit Research Institute, Tel Aviv, and his coauthors.

Adjustment for age did not significantly alter the interaction between LDL-C levels and the risk of adverse cardiac events (JAMA Intern Med. 2016 Jun 20. doi: 10.1001/jamainternmed.2016.2751).

“The question of the association between achieved LDL-C levels and major adverse cardiac events for secondary prevention has become highly relevant, particularly in the real-world context of patients excluded from [randomized, controlled trials],” the authors wrote, suggesting that their data only partially support recent claims that lower LDL-C is better for cardiac outcomes.

“Our findings of significantly lower risk of MACEs associated with achieved LDL-C level of less than 100.0 mg/dL but not with achieved LDL-C of less than 70.0 mg/dL suggest a target for long-term statin treatment.”

The study was funded by the Clalit Research Institute. No conflicts of interest were reported.

Researchers have identified a “sweet spot” target for reducing low-density lipoprotein cholesterol levels with statin therapy that is associated with the lowest risk of adverse cardiac outcomes.

A study published online June 20 in JAMA Internal Medicine analyzed data from an Israeli health care organization between 2009-2013 and identified 31,619 patients with ischemic heart disease, aged 30-84 years, who were being treated with statins and were at least 80% adherent to the medication regime.

Louise Koenig/Frontline Medical News

The analysis showed individuals who achieved a “moderate” LDL-C level – between 70.1-100.0 mg/dL – after 1 year of statin treatment had an 11% lower incidence of major adverse cardiac events, compared with those with a “high” LDL-C level – between 100.1-130.0 mg/dL (95% confidence interval, 0.84-0.94; P less than .001).

However researchers observed no significant difference in the risk of adverse cardiac events between the moderate group and those who achieved a “low” LDL-C equal to or less than 70.0mg/dL (hazard ratio, 1.02; 95% CI, 0.97-1.07; P = .54).

In a further analysis that included 54,884 individuals who were at least 50% adherent to their statin therapy, there was a slightly increased risk of major cardiac events in patients who achieved a low LDL-C, compared with those in the moderate LDL-C group, and a significant 13% reduction in risk in the moderate LDL-C group, compared with the high LDL-C group.

“Whereas this may reflect clinical risk of low levels of LDL-C, these results further support the main findings of this study that achieving a level below 70 mg/dL is not beneficial for all patients,” wrote Dr. Morton Leibowitz, from the Clalit Research Institute, Tel Aviv, and his coauthors.

Adjustment for age did not significantly alter the interaction between LDL-C levels and the risk of adverse cardiac events (JAMA Intern Med. 2016 Jun 20. doi: 10.1001/jamainternmed.2016.2751).

“The question of the association between achieved LDL-C levels and major adverse cardiac events for secondary prevention has become highly relevant, particularly in the real-world context of patients excluded from [randomized, controlled trials],” the authors wrote, suggesting that their data only partially support recent claims that lower LDL-C is better for cardiac outcomes.

“Our findings of significantly lower risk of MACEs associated with achieved LDL-C level of less than 100.0 mg/dL but not with achieved LDL-C of less than 70.0 mg/dL suggest a target for long-term statin treatment.”

The study was funded by the Clalit Research Institute. No conflicts of interest were reported.

Despite following guidelines aimed at reducing the likelihood of tuberculosis infection in patients with psoriasis treated with tumor necrosis factor antagonists, a French study has identified a number of active TB cases in this patient group.

The nationwide retrospective study identified 12 cases of tuberculosis in individuals with psoriasis during treatment with a TNF-antagonist between 2006 and 2014 – 9 men and 3 women, whose mean age was 49 years – according to Dr. E. Guinard of the dermatology service, CHU Toulouse Larrey at Paul Sabatier University, Toulouse, France, and associates (J Eur Acad Dermatol Venereol. 2016 Jun 3. doi: 10.1111/jdv.13633).

The investigators identified the cases from a national pharmacosurveillance database and by contacting members of the psoriasis research group in France’s national dermatology society and the national college of French dermatology professors.

Before starting anti-TNF therapy, all 12 patients had been screened for latent TB based on French guidelines: three patients were tested with the tuberculosis skin test alone, six were tested with QuantiFERON-TB Gold test, and three patients had both the skin test and QuantiFERON-TB. Each had a pretreatment chest x-ray.

Based on this testing, three were diagnosed with latent TB and received chemoprophylaxis; the other nine patients tested negative.

Information on TB risk factors was not available for all 12 cases, but three people had had contact with someone with TB during treatment. Three of the individuals had traveled to or were born in areas where TB was endemic, and one patient had had a case of TB in the family in the year before starting anti-TNF therapy. Nine patients had a known history of BCG vaccination, the investigators said.

The time between starting anti-TNF therapy and the appearance of TB symptoms ranged from 2 to 176 weeks (mean, 23 weeks), and diagnosis was based on clinical signs – such as fever, night sweats, and cough – and on imaging and laboratory investigations. Most (10) of the cases were extrapulmonary presentations, and two were pleuropulmonary. When diagnosed with tuberculosis, seven of the patients were being treated with infliximab, four were being treated with adalimumab, and one was being treated with certolizumab. All stopped anti-TNF therapy once they were diagnosed with tuberculosis.

Dr. Guinard and associates noted that the low sensitivity of Mycobacterium tuberculosis diagnostic tests was “a striking feature” of these cases. Only one-third of the patients showed a positive direct Ziehl-Neelsen stain for acid-fast bacilli and half had a positive culture.

“According to this study and published experience, in a patient with suggestive symptoms, a negative Mycobacterium tuberculosis test should not delay the decision to initiate anti-tuberculosis treatment,” they wrote. “This is particularly important considering the high mortality of tuberculosis in patients treated with TNF antagonists,” which ranges from 6%-17%, they added.

Two of the twelve patients – aged 77 and 32 years – died of disseminated tuberculosis disease during treatment for TB.

“This is the largest study of tuberculosis in psoriasis patients treated with TNF antagonists,” according to the authors.

No conflicts of interest were declared, and the study had no funding source.

Despite following guidelines aimed at reducing the likelihood of tuberculosis infection in patients with psoriasis treated with tumor necrosis factor antagonists, a French study has identified a number of active TB cases in this patient group.

The nationwide retrospective study identified 12 cases of tuberculosis in individuals with psoriasis during treatment with a TNF-antagonist between 2006 and 2014 – 9 men and 3 women, whose mean age was 49 years – according to Dr. E. Guinard of the dermatology service, CHU Toulouse Larrey at Paul Sabatier University, Toulouse, France, and associates (J Eur Acad Dermatol Venereol. 2016 Jun 3. doi: 10.1111/jdv.13633).

The investigators identified the cases from a national pharmacosurveillance database and by contacting members of the psoriasis research group in France’s national dermatology society and the national college of French dermatology professors.

Before starting anti-TNF therapy, all 12 patients had been screened for latent TB based on French guidelines: three patients were tested with the tuberculosis skin test alone, six were tested with QuantiFERON-TB Gold test, and three patients had both the skin test and QuantiFERON-TB. Each had a pretreatment chest x-ray.

Based on this testing, three were diagnosed with latent TB and received chemoprophylaxis; the other nine patients tested negative.

Information on TB risk factors was not available for all 12 cases, but three people had had contact with someone with TB during treatment. Three of the individuals had traveled to or were born in areas where TB was endemic, and one patient had had a case of TB in the family in the year before starting anti-TNF therapy. Nine patients had a known history of BCG vaccination, the investigators said.

The time between starting anti-TNF therapy and the appearance of TB symptoms ranged from 2 to 176 weeks (mean, 23 weeks), and diagnosis was based on clinical signs – such as fever, night sweats, and cough – and on imaging and laboratory investigations. Most (10) of the cases were extrapulmonary presentations, and two were pleuropulmonary. When diagnosed with tuberculosis, seven of the patients were being treated with infliximab, four were being treated with adalimumab, and one was being treated with certolizumab. All stopped anti-TNF therapy once they were diagnosed with tuberculosis.

Dr. Guinard and associates noted that the low sensitivity of Mycobacterium tuberculosis diagnostic tests was “a striking feature” of these cases. Only one-third of the patients showed a positive direct Ziehl-Neelsen stain for acid-fast bacilli and half had a positive culture.

“According to this study and published experience, in a patient with suggestive symptoms, a negative Mycobacterium tuberculosis test should not delay the decision to initiate anti-tuberculosis treatment,” they wrote. “This is particularly important considering the high mortality of tuberculosis in patients treated with TNF antagonists,” which ranges from 6%-17%, they added.

Two of the twelve patients – aged 77 and 32 years – died of disseminated tuberculosis disease during treatment for TB.

“This is the largest study of tuberculosis in psoriasis patients treated with TNF antagonists,” according to the authors.

No conflicts of interest were declared, and the study had no funding source.

Despite following guidelines aimed at reducing the likelihood of tuberculosis infection in patients with psoriasis treated with tumor necrosis factor antagonists, a French study has identified a number of active TB cases in this patient group.

The nationwide retrospective study identified 12 cases of tuberculosis in individuals with psoriasis during treatment with a TNF-antagonist between 2006 and 2014 – 9 men and 3 women, whose mean age was 49 years – according to Dr. E. Guinard of the dermatology service, CHU Toulouse Larrey at Paul Sabatier University, Toulouse, France, and associates (J Eur Acad Dermatol Venereol. 2016 Jun 3. doi: 10.1111/jdv.13633).

The investigators identified the cases from a national pharmacosurveillance database and by contacting members of the psoriasis research group in France’s national dermatology society and the national college of French dermatology professors.

Before starting anti-TNF therapy, all 12 patients had been screened for latent TB based on French guidelines: three patients were tested with the tuberculosis skin test alone, six were tested with QuantiFERON-TB Gold test, and three patients had both the skin test and QuantiFERON-TB. Each had a pretreatment chest x-ray.

Based on this testing, three were diagnosed with latent TB and received chemoprophylaxis; the other nine patients tested negative.

Information on TB risk factors was not available for all 12 cases, but three people had had contact with someone with TB during treatment. Three of the individuals had traveled to or were born in areas where TB was endemic, and one patient had had a case of TB in the family in the year before starting anti-TNF therapy. Nine patients had a known history of BCG vaccination, the investigators said.

The time between starting anti-TNF therapy and the appearance of TB symptoms ranged from 2 to 176 weeks (mean, 23 weeks), and diagnosis was based on clinical signs – such as fever, night sweats, and cough – and on imaging and laboratory investigations. Most (10) of the cases were extrapulmonary presentations, and two were pleuropulmonary. When diagnosed with tuberculosis, seven of the patients were being treated with infliximab, four were being treated with adalimumab, and one was being treated with certolizumab. All stopped anti-TNF therapy once they were diagnosed with tuberculosis.

Dr. Guinard and associates noted that the low sensitivity of Mycobacterium tuberculosis diagnostic tests was “a striking feature” of these cases. Only one-third of the patients showed a positive direct Ziehl-Neelsen stain for acid-fast bacilli and half had a positive culture.

“According to this study and published experience, in a patient with suggestive symptoms, a negative Mycobacterium tuberculosis test should not delay the decision to initiate anti-tuberculosis treatment,” they wrote. “This is particularly important considering the high mortality of tuberculosis in patients treated with TNF antagonists,” which ranges from 6%-17%, they added.

Two of the twelve patients – aged 77 and 32 years – died of disseminated tuberculosis disease during treatment for TB.

“This is the largest study of tuberculosis in psoriasis patients treated with TNF antagonists,” according to the authors.

No conflicts of interest were declared, and the study had no funding source.

The combination weight-loss drug phentermine plus topiramate is associated with the highest odds of individuals being able to lose 5% of their body weight within 1 year, according to a meta-analysis comparing outcomes and adverse events for orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, and liraglutide.

Researchers analyzed 28 randomized placebo- or active-controlled clinical trials involving a total of 29,018 participants and found those who took phentermine-topiramate had a ninefold greater likelihood of achieving a 5% weight loss by 1 year than did those on placebo, according to a paper published in the June 14 issue of JAMA.

Liraglutide showed the second-highest odds of achieving a 5% weight loss at 1 year (odds ratio, 5.54), followed by naltrexone-bupropion (OR, 3.96), lorcaserin (OR, 3.10), and orlistat (OR, 2.70).

Nearly one-quarter of individuals on placebo achieved at least a 5% weight loss by 1 year, compared with three-quarters of individuals taking phentermine-topiramate, 63% of those taking liraglutide, 55% taking naltrexone-bupropion, 49% taking lorcaserin, and 44% taking orlistat (JAMA 2016;315:2424-34. doi: 10.1001/jama.2016.7602).

Of those on placebo, only 9% achieved at least a 10% weight loss at 1 year, compared with 54% of patients taking phentermine-topiramate, 34% of patients on liraglutide, 30% of patients on naltrexone-bupropion, 25% of those taking lorcaserin, and 20% of those taking orlistat.

Phentermine-topiramate was also associated with the greatest weight loss, compared with placebo, with patients losing a mean of 8.8 kg vs. 5.2 kg with liraglutide, 5 kg with naltrexone-bupropion, 3.2 kg with lorcaserin, and 2.6 kg with orlistat.

While all active drugs were associated with a higher rate of discontinuation because of adverse events than was seen with placebo, liraglutide was associated with the greatest risk of discontinuation, compared with placebo, followed by naltrexone-bupropion, phentermine-topiramate, orlistat, and then lorcaserin.

Dr. Rohan Khera of the department of internal medicine at the University of Iowa, Iowa City, and coauthors wrote that pharmacologic treatment decisions should consider coexisting medical conditions that might influence for or against a particular choice for weight loss.

“For example, liraglutide may be a more appropriate agent in people with diabetes because of its glucose-lowering effects,” they wrote. “Conversely, naltrexone-bupropion in patients with chronic opiate or alcohol dependence may be associated with neuropsychiatric complications.

“Ultimately, given the differences in safety, efficacy, and response to therapy, the ideal approach to weight loss should be highly individualized, identifying appropriate candidates for pharmacotherapy, behavioral interventions, and surgical interventions.”

Two study authors were supported by a grant from the National Library of Medicine or the National Institute of Diabetes and Digestive and Kidney Diseases. One author reported receiving funding, participating on advisory committees, and serving as a consultant with a range of pharmaceutical manufacturers, as well as being a cofounder of Liponexus. Another author reported research support from NovoNordisk for research on liraglutide. No other disclosures were reported.

The combination weight-loss drug phentermine plus topiramate is associated with the highest odds of individuals being able to lose 5% of their body weight within 1 year, according to a meta-analysis comparing outcomes and adverse events for orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, and liraglutide.

Researchers analyzed 28 randomized placebo- or active-controlled clinical trials involving a total of 29,018 participants and found those who took phentermine-topiramate had a ninefold greater likelihood of achieving a 5% weight loss by 1 year than did those on placebo, according to a paper published in the June 14 issue of JAMA.

Liraglutide showed the second-highest odds of achieving a 5% weight loss at 1 year (odds ratio, 5.54), followed by naltrexone-bupropion (OR, 3.96), lorcaserin (OR, 3.10), and orlistat (OR, 2.70).

Nearly one-quarter of individuals on placebo achieved at least a 5% weight loss by 1 year, compared with three-quarters of individuals taking phentermine-topiramate, 63% of those taking liraglutide, 55% taking naltrexone-bupropion, 49% taking lorcaserin, and 44% taking orlistat (JAMA 2016;315:2424-34. doi: 10.1001/jama.2016.7602).

Of those on placebo, only 9% achieved at least a 10% weight loss at 1 year, compared with 54% of patients taking phentermine-topiramate, 34% of patients on liraglutide, 30% of patients on naltrexone-bupropion, 25% of those taking lorcaserin, and 20% of those taking orlistat.

Phentermine-topiramate was also associated with the greatest weight loss, compared with placebo, with patients losing a mean of 8.8 kg vs. 5.2 kg with liraglutide, 5 kg with naltrexone-bupropion, 3.2 kg with lorcaserin, and 2.6 kg with orlistat.

While all active drugs were associated with a higher rate of discontinuation because of adverse events than was seen with placebo, liraglutide was associated with the greatest risk of discontinuation, compared with placebo, followed by naltrexone-bupropion, phentermine-topiramate, orlistat, and then lorcaserin.

Dr. Rohan Khera of the department of internal medicine at the University of Iowa, Iowa City, and coauthors wrote that pharmacologic treatment decisions should consider coexisting medical conditions that might influence for or against a particular choice for weight loss.

“For example, liraglutide may be a more appropriate agent in people with diabetes because of its glucose-lowering effects,” they wrote. “Conversely, naltrexone-bupropion in patients with chronic opiate or alcohol dependence may be associated with neuropsychiatric complications.

“Ultimately, given the differences in safety, efficacy, and response to therapy, the ideal approach to weight loss should be highly individualized, identifying appropriate candidates for pharmacotherapy, behavioral interventions, and surgical interventions.”

Two study authors were supported by a grant from the National Library of Medicine or the National Institute of Diabetes and Digestive and Kidney Diseases. One author reported receiving funding, participating on advisory committees, and serving as a consultant with a range of pharmaceutical manufacturers, as well as being a cofounder of Liponexus. Another author reported research support from NovoNordisk for research on liraglutide. No other disclosures were reported.

The combination weight-loss drug phentermine plus topiramate is associated with the highest odds of individuals being able to lose 5% of their body weight within 1 year, according to a meta-analysis comparing outcomes and adverse events for orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, and liraglutide.

Researchers analyzed 28 randomized placebo- or active-controlled clinical trials involving a total of 29,018 participants and found those who took phentermine-topiramate had a ninefold greater likelihood of achieving a 5% weight loss by 1 year than did those on placebo, according to a paper published in the June 14 issue of JAMA.

Liraglutide showed the second-highest odds of achieving a 5% weight loss at 1 year (odds ratio, 5.54), followed by naltrexone-bupropion (OR, 3.96), lorcaserin (OR, 3.10), and orlistat (OR, 2.70).

Nearly one-quarter of individuals on placebo achieved at least a 5% weight loss by 1 year, compared with three-quarters of individuals taking phentermine-topiramate, 63% of those taking liraglutide, 55% taking naltrexone-bupropion, 49% taking lorcaserin, and 44% taking orlistat (JAMA 2016;315:2424-34. doi: 10.1001/jama.2016.7602).

Of those on placebo, only 9% achieved at least a 10% weight loss at 1 year, compared with 54% of patients taking phentermine-topiramate, 34% of patients on liraglutide, 30% of patients on naltrexone-bupropion, 25% of those taking lorcaserin, and 20% of those taking orlistat.

Phentermine-topiramate was also associated with the greatest weight loss, compared with placebo, with patients losing a mean of 8.8 kg vs. 5.2 kg with liraglutide, 5 kg with naltrexone-bupropion, 3.2 kg with lorcaserin, and 2.6 kg with orlistat.

While all active drugs were associated with a higher rate of discontinuation because of adverse events than was seen with placebo, liraglutide was associated with the greatest risk of discontinuation, compared with placebo, followed by naltrexone-bupropion, phentermine-topiramate, orlistat, and then lorcaserin.

Dr. Rohan Khera of the department of internal medicine at the University of Iowa, Iowa City, and coauthors wrote that pharmacologic treatment decisions should consider coexisting medical conditions that might influence for or against a particular choice for weight loss.

“For example, liraglutide may be a more appropriate agent in people with diabetes because of its glucose-lowering effects,” they wrote. “Conversely, naltrexone-bupropion in patients with chronic opiate or alcohol dependence may be associated with neuropsychiatric complications.

“Ultimately, given the differences in safety, efficacy, and response to therapy, the ideal approach to weight loss should be highly individualized, identifying appropriate candidates for pharmacotherapy, behavioral interventions, and surgical interventions.”

Two study authors were supported by a grant from the National Library of Medicine or the National Institute of Diabetes and Digestive and Kidney Diseases. One author reported receiving funding, participating on advisory committees, and serving as a consultant with a range of pharmaceutical manufacturers, as well as being a cofounder of Liponexus. Another author reported research support from NovoNordisk for research on liraglutide. No other disclosures were reported.

More than half of the patients treated with the interleukin-17A antagonist, ixekizumab, achieved full resolution of skin plaques after a year of 2- to 4-week dosing, according to the latest analysis of data from the three UNCOVER trials of almost 4,000 patients with moderate to severe psoriasis.

The results of the three randomized, double-blind placebo-controlled pivotal trials were published online in the New England Journal of Medicine (doi: 10.1056/NEJMoa1512711).

Ixekizumab was approved in March for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy; it is marketed as Taltz by Eli Lilly. Some of the UNCOVER data have been previously reported. The UNCOVER studies were conducted at more than 100 sites in 21 countries.

Patients in the UNCOVER trials were randomized to 80 mg of ixekizumab every 2 weeks after a starting dose of 160 mg, 80 mg every 4 weeks after the same starting dose, or subcutaneous placebo injections, for 12 weeks.

In the UNCOVER-2 and UNCOVER-3 trials, additional cohorts were also randomized to twice-weekly etanercept (50 mg). All three trials also included a long-term extension period to 60 weeks, which was randomly assigned in UNCOVER-3 (where patients received 80 mg of ixekizumab every 4 weeks), or was implemented for all patients who responded to ixekizumab in the other two trials (where patients were randomized to 80 mg every 4 or 12 weeks, or placebo).

In the UNCOVER-1 trial in 1,296 patients, 89.1% of patients in the 2-week dosing group and 82.6% of the 4-week dosing group had achieved a 75% reduction in the Psoriasis Area and Severity Index score (PASI 75) by week 12, compared with 3.9% in the placebo group (P less than .0001 for all). Similarly, 35.3% of patients in the 2-week dosing group and 33.6% of those in the 4-week dosing group achieved a PASI score of 100 by week 12.

The high response rates seen during the induction period “were generally maintained during the long-term extension period in UNCOVER-3,” wrote Dr. Kenneth B. Gordon, professor of dermatology, Northwestern University, Chicago, and his coauthors. In the analysis of the long-term data from UNCOVER-3, the researchers reported that by week 60, 55% of patients receiving 80 mg of ixekizumab every 2 weeks during the induction period had achieved a PASI 100, and 52% of patients receiving ixekizumab every 4 weeks during the induction period had achieved a PASI 100.

Patients randomized to 80 mg of ixekizumab every 12 weeks after the first 12 weeks of treatment also showed significant long-term responses in the UNCOVER-1 and -2 trials. Nearly half (49.1%) of those who were initiated on 2-week dosing and 44.9% of those initiated on 4-week dosing achieved a PASI score of 75 on the 12-week dosing schedule, compared with 8%-9% of those randomized to placebo from week 12 through week 60.

The authors concluded that ixekizumab “provided high levels of clinical response at week 12 and through week 60,” adding, however, that “as with any treatment, the benefits need to be weighed against the adverse events, and the safety profile of longer-term treatment with ixekizumab should be examined.”

Although low serum IL-17 levels have previously been linked with cardiovascular disease, the study found no significant differences between the treatment and placebo groups in adverse cardiovascular events. Candidal infections were more common among those treated with ixekizumab, “a finding that is consistent with the role of IL-17A in the mucocutaneous defense against fungal infections,” they wrote.

There were 11 cases of inflammatory bowel disease reported among patients during treatment with ixekizumab and another three cases in patients receiving placebo during a randomized withdrawal period, who had received ixekizumab during the induction* period. These results “suggest that further evaluation is needed to understand the relationship between IL-17A inhibitors and inflammatory bowel disease,” the investigators said.

The authors of the study include Eli Lilly employees, several of whom also have stock options; the other authors declared a range of funding, advisory board positions, and speakers fees from pharmaceutical companies, including Eli Lilly. The UNCOVER studies were sponsored by Eli Lilly.

*A previous version of this article misstated the period during which three placebo patients received ixekizumab.

More than half of the patients treated with the interleukin-17A antagonist, ixekizumab, achieved full resolution of skin plaques after a year of 2- to 4-week dosing, according to the latest analysis of data from the three UNCOVER trials of almost 4,000 patients with moderate to severe psoriasis.

The results of the three randomized, double-blind placebo-controlled pivotal trials were published online in the New England Journal of Medicine (doi: 10.1056/NEJMoa1512711).

Ixekizumab was approved in March for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy; it is marketed as Taltz by Eli Lilly. Some of the UNCOVER data have been previously reported. The UNCOVER studies were conducted at more than 100 sites in 21 countries.

Patients in the UNCOVER trials were randomized to 80 mg of ixekizumab every 2 weeks after a starting dose of 160 mg, 80 mg every 4 weeks after the same starting dose, or subcutaneous placebo injections, for 12 weeks.

In the UNCOVER-2 and UNCOVER-3 trials, additional cohorts were also randomized to twice-weekly etanercept (50 mg). All three trials also included a long-term extension period to 60 weeks, which was randomly assigned in UNCOVER-3 (where patients received 80 mg of ixekizumab every 4 weeks), or was implemented for all patients who responded to ixekizumab in the other two trials (where patients were randomized to 80 mg every 4 or 12 weeks, or placebo).

In the UNCOVER-1 trial in 1,296 patients, 89.1% of patients in the 2-week dosing group and 82.6% of the 4-week dosing group had achieved a 75% reduction in the Psoriasis Area and Severity Index score (PASI 75) by week 12, compared with 3.9% in the placebo group (P less than .0001 for all). Similarly, 35.3% of patients in the 2-week dosing group and 33.6% of those in the 4-week dosing group achieved a PASI score of 100 by week 12.

The high response rates seen during the induction period “were generally maintained during the long-term extension period in UNCOVER-3,” wrote Dr. Kenneth B. Gordon, professor of dermatology, Northwestern University, Chicago, and his coauthors. In the analysis of the long-term data from UNCOVER-3, the researchers reported that by week 60, 55% of patients receiving 80 mg of ixekizumab every 2 weeks during the induction period had achieved a PASI 100, and 52% of patients receiving ixekizumab every 4 weeks during the induction period had achieved a PASI 100.

Patients randomized to 80 mg of ixekizumab every 12 weeks after the first 12 weeks of treatment also showed significant long-term responses in the UNCOVER-1 and -2 trials. Nearly half (49.1%) of those who were initiated on 2-week dosing and 44.9% of those initiated on 4-week dosing achieved a PASI score of 75 on the 12-week dosing schedule, compared with 8%-9% of those randomized to placebo from week 12 through week 60.

The authors concluded that ixekizumab “provided high levels of clinical response at week 12 and through week 60,” adding, however, that “as with any treatment, the benefits need to be weighed against the adverse events, and the safety profile of longer-term treatment with ixekizumab should be examined.”

Although low serum IL-17 levels have previously been linked with cardiovascular disease, the study found no significant differences between the treatment and placebo groups in adverse cardiovascular events. Candidal infections were more common among those treated with ixekizumab, “a finding that is consistent with the role of IL-17A in the mucocutaneous defense against fungal infections,” they wrote.

There were 11 cases of inflammatory bowel disease reported among patients during treatment with ixekizumab and another three cases in patients receiving placebo during a randomized withdrawal period, who had received ixekizumab during the induction* period. These results “suggest that further evaluation is needed to understand the relationship between IL-17A inhibitors and inflammatory bowel disease,” the investigators said.

The authors of the study include Eli Lilly employees, several of whom also have stock options; the other authors declared a range of funding, advisory board positions, and speakers fees from pharmaceutical companies, including Eli Lilly. The UNCOVER studies were sponsored by Eli Lilly.

*A previous version of this article misstated the period during which three placebo patients received ixekizumab.

More than half of the patients treated with the interleukin-17A antagonist, ixekizumab, achieved full resolution of skin plaques after a year of 2- to 4-week dosing, according to the latest analysis of data from the three UNCOVER trials of almost 4,000 patients with moderate to severe psoriasis.

The results of the three randomized, double-blind placebo-controlled pivotal trials were published online in the New England Journal of Medicine (doi: 10.1056/NEJMoa1512711).

Ixekizumab was approved in March for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy; it is marketed as Taltz by Eli Lilly. Some of the UNCOVER data have been previously reported. The UNCOVER studies were conducted at more than 100 sites in 21 countries.

Patients in the UNCOVER trials were randomized to 80 mg of ixekizumab every 2 weeks after a starting dose of 160 mg, 80 mg every 4 weeks after the same starting dose, or subcutaneous placebo injections, for 12 weeks.

In the UNCOVER-2 and UNCOVER-3 trials, additional cohorts were also randomized to twice-weekly etanercept (50 mg). All three trials also included a long-term extension period to 60 weeks, which was randomly assigned in UNCOVER-3 (where patients received 80 mg of ixekizumab every 4 weeks), or was implemented for all patients who responded to ixekizumab in the other two trials (where patients were randomized to 80 mg every 4 or 12 weeks, or placebo).

In the UNCOVER-1 trial in 1,296 patients, 89.1% of patients in the 2-week dosing group and 82.6% of the 4-week dosing group had achieved a 75% reduction in the Psoriasis Area and Severity Index score (PASI 75) by week 12, compared with 3.9% in the placebo group (P less than .0001 for all). Similarly, 35.3% of patients in the 2-week dosing group and 33.6% of those in the 4-week dosing group achieved a PASI score of 100 by week 12.

The high response rates seen during the induction period “were generally maintained during the long-term extension period in UNCOVER-3,” wrote Dr. Kenneth B. Gordon, professor of dermatology, Northwestern University, Chicago, and his coauthors. In the analysis of the long-term data from UNCOVER-3, the researchers reported that by week 60, 55% of patients receiving 80 mg of ixekizumab every 2 weeks during the induction period had achieved a PASI 100, and 52% of patients receiving ixekizumab every 4 weeks during the induction period had achieved a PASI 100.

Patients randomized to 80 mg of ixekizumab every 12 weeks after the first 12 weeks of treatment also showed significant long-term responses in the UNCOVER-1 and -2 trials. Nearly half (49.1%) of those who were initiated on 2-week dosing and 44.9% of those initiated on 4-week dosing achieved a PASI score of 75 on the 12-week dosing schedule, compared with 8%-9% of those randomized to placebo from week 12 through week 60.

The authors concluded that ixekizumab “provided high levels of clinical response at week 12 and through week 60,” adding, however, that “as with any treatment, the benefits need to be weighed against the adverse events, and the safety profile of longer-term treatment with ixekizumab should be examined.”

Although low serum IL-17 levels have previously been linked with cardiovascular disease, the study found no significant differences between the treatment and placebo groups in adverse cardiovascular events. Candidal infections were more common among those treated with ixekizumab, “a finding that is consistent with the role of IL-17A in the mucocutaneous defense against fungal infections,” they wrote.

There were 11 cases of inflammatory bowel disease reported among patients during treatment with ixekizumab and another three cases in patients receiving placebo during a randomized withdrawal period, who had received ixekizumab during the induction* period. These results “suggest that further evaluation is needed to understand the relationship between IL-17A inhibitors and inflammatory bowel disease,” the investigators said.

The authors of the study include Eli Lilly employees, several of whom also have stock options; the other authors declared a range of funding, advisory board positions, and speakers fees from pharmaceutical companies, including Eli Lilly. The UNCOVER studies were sponsored by Eli Lilly.

*A previous version of this article misstated the period during which three placebo patients received ixekizumab.

Applying the more stringent SPRINT criteria to a general population of persons with hypertension would yield a significant reduction in the number of people meeting their treatment goals, although those who do would achieve a significant reduction in their risk of cardiovascular disease, a study published June 13 in the Journal of the American College of Cardiology has found.

Min Jung Ko, Ph.D., of the National Evidence-Based Healthcare Collaborating Agency in Seoul, Korea, and coauthors explored the relative impacts of SPRINT target of less than 120 mm Hg for hypertension treatments with the 2014 hypertension recommendations of the Eighth Joint National Committee of less than 140 mm Hg, using data from 13,346 individuals in the Korean National Health and Nutrition Examination Survey of 2008-2013, and 67,965 individuals in the Korean National Health Insurance Service health examinee cohort of 2007.

©Ingram Publishing/thinkstockphotos.com

The investigators found that 11.9% of adults with hypertension would meet the treatment goals of the SPRINT criteria, compared with 70.8% who would meet the 2014 recommendations.

However, the analysis showed that those who met the more aggressive SPRINT treatment goal of systolic BP below 120 mm Hg also had the lowest 10-year risk of a major cardiovascular event (6.2%), compared with 7.7% in those who met the 2014 targets but not the SPRINT targets, and 9.4% in those who failed to meet the 2014 treatment targets (J Am Coll Cardiol. 2016 Jun 13. doi 10.1016/j.jacc.2016.03.572).

After adjustment for factors such as age, diabetes, chronic kidney disease, hyperlipidemia, body mass index, and smoking, the least-controlled group showed a 62% increase in the risk of cardiovascular events, compared with the SPRINT criteria group. Those who met the 2014 criteria had a 17% greater risk than those who met the SPRINT criteria.

“Despite greater cardiovascular protection with intensive BP lowering, achieving SPRINT-defined BP goals might not be easy or practical because the target BP was not met in more than one-half of the participants in the intensive-treatment group,” the authors wrote.

Individuals who were older, female, or had diabetes, chronic kidney disease, or prevalent cardiovascular disease were more likely to meet the stricter goals of SPRINT (Systolic Blood Pressure Intervention Trial), in which combined cardiovascular events occurred in 5.2% of patients treated to a target systolic blood pressure of less than 120 mm Hg and 6.8% of patients treated to a target of less than 140 mm Hg (N Engl J Med. 2015;373:2103-16).

Researchers also noted a significant linear association between lesser blood pressure control and an increased risk of myocardial infarction and stroke, although there was no significant trend seen relating to cardiovascular or all-cause mortality. The authors noted that this was the opposite to what was observed in the original SPRINT trial, where there was a reduction in cardiovascular mortality and heart failure but only a modest, nonsignificant impact on MI or stroke.

“Although the exact reasons remain unclear, this discrepancy might be explained in part by differences in study design, population characteristics, clinical practice pattern, or race or ethnic groups,” they suggested. “The generalizability of the SPRINT experience to multiple groups of various ethnic backgrounds warrants further investigations and is likely to be of considerable interest.”

Unlike the SPRINT trial, the Korean analysis did not look into the potential adverse effects of more aggressive blood pressure–lowering, but the authors noted that the SPRINT trial did see an increased incidence of more serious adverse events, including hypotension, syncope, and acute kidney injury.

“Therefore, beyond the BP target per se, several important factors should be considered for optimal BP management in the contemporary medical setting; for example, an integrated and systematic assessment of combined risk factors and baseline cardiovascular risk, concomitant preventive medical therapies, cost-effectiveness, clinician-patient discussions of the potential benefits and harms, or the clinical judgment of the treating physician.”

The National Evidence-Based Healthcare Collaborating Agency, Seoul, South Korea, funded the study. No conflicts of interest were declared.

Applying the more stringent SPRINT criteria to a general population of persons with hypertension would yield a significant reduction in the number of people meeting their treatment goals, although those who do would achieve a significant reduction in their risk of cardiovascular disease, a study published June 13 in the Journal of the American College of Cardiology has found.

Min Jung Ko, Ph.D., of the National Evidence-Based Healthcare Collaborating Agency in Seoul, Korea, and coauthors explored the relative impacts of SPRINT target of less than 120 mm Hg for hypertension treatments with the 2014 hypertension recommendations of the Eighth Joint National Committee of less than 140 mm Hg, using data from 13,346 individuals in the Korean National Health and Nutrition Examination Survey of 2008-2013, and 67,965 individuals in the Korean National Health Insurance Service health examinee cohort of 2007.

©Ingram Publishing/thinkstockphotos.com

The investigators found that 11.9% of adults with hypertension would meet the treatment goals of the SPRINT criteria, compared with 70.8% who would meet the 2014 recommendations.

However, the analysis showed that those who met the more aggressive SPRINT treatment goal of systolic BP below 120 mm Hg also had the lowest 10-year risk of a major cardiovascular event (6.2%), compared with 7.7% in those who met the 2014 targets but not the SPRINT targets, and 9.4% in those who failed to meet the 2014 treatment targets (J Am Coll Cardiol. 2016 Jun 13. doi 10.1016/j.jacc.2016.03.572).

After adjustment for factors such as age, diabetes, chronic kidney disease, hyperlipidemia, body mass index, and smoking, the least-controlled group showed a 62% increase in the risk of cardiovascular events, compared with the SPRINT criteria group. Those who met the 2014 criteria had a 17% greater risk than those who met the SPRINT criteria.

“Despite greater cardiovascular protection with intensive BP lowering, achieving SPRINT-defined BP goals might not be easy or practical because the target BP was not met in more than one-half of the participants in the intensive-treatment group,” the authors wrote.

Individuals who were older, female, or had diabetes, chronic kidney disease, or prevalent cardiovascular disease were more likely to meet the stricter goals of SPRINT (Systolic Blood Pressure Intervention Trial), in which combined cardiovascular events occurred in 5.2% of patients treated to a target systolic blood pressure of less than 120 mm Hg and 6.8% of patients treated to a target of less than 140 mm Hg (N Engl J Med. 2015;373:2103-16).

Researchers also noted a significant linear association between lesser blood pressure control and an increased risk of myocardial infarction and stroke, although there was no significant trend seen relating to cardiovascular or all-cause mortality. The authors noted that this was the opposite to what was observed in the original SPRINT trial, where there was a reduction in cardiovascular mortality and heart failure but only a modest, nonsignificant impact on MI or stroke.

“Although the exact reasons remain unclear, this discrepancy might be explained in part by differences in study design, population characteristics, clinical practice pattern, or race or ethnic groups,” they suggested. “The generalizability of the SPRINT experience to multiple groups of various ethnic backgrounds warrants further investigations and is likely to be of considerable interest.”

Unlike the SPRINT trial, the Korean analysis did not look into the potential adverse effects of more aggressive blood pressure–lowering, but the authors noted that the SPRINT trial did see an increased incidence of more serious adverse events, including hypotension, syncope, and acute kidney injury.

“Therefore, beyond the BP target per se, several important factors should be considered for optimal BP management in the contemporary medical setting; for example, an integrated and systematic assessment of combined risk factors and baseline cardiovascular risk, concomitant preventive medical therapies, cost-effectiveness, clinician-patient discussions of the potential benefits and harms, or the clinical judgment of the treating physician.”

The National Evidence-Based Healthcare Collaborating Agency, Seoul, South Korea, funded the study. No conflicts of interest were declared.

Applying the more stringent SPRINT criteria to a general population of persons with hypertension would yield a significant reduction in the number of people meeting their treatment goals, although those who do would achieve a significant reduction in their risk of cardiovascular disease, a study published June 13 in the Journal of the American College of Cardiology has found.

Min Jung Ko, Ph.D., of the National Evidence-Based Healthcare Collaborating Agency in Seoul, Korea, and coauthors explored the relative impacts of SPRINT target of less than 120 mm Hg for hypertension treatments with the 2014 hypertension recommendations of the Eighth Joint National Committee of less than 140 mm Hg, using data from 13,346 individuals in the Korean National Health and Nutrition Examination Survey of 2008-2013, and 67,965 individuals in the Korean National Health Insurance Service health examinee cohort of 2007.

©Ingram Publishing/thinkstockphotos.com

The investigators found that 11.9% of adults with hypertension would meet the treatment goals of the SPRINT criteria, compared with 70.8% who would meet the 2014 recommendations.

However, the analysis showed that those who met the more aggressive SPRINT treatment goal of systolic BP below 120 mm Hg also had the lowest 10-year risk of a major cardiovascular event (6.2%), compared with 7.7% in those who met the 2014 targets but not the SPRINT targets, and 9.4% in those who failed to meet the 2014 treatment targets (J Am Coll Cardiol. 2016 Jun 13. doi 10.1016/j.jacc.2016.03.572).

After adjustment for factors such as age, diabetes, chronic kidney disease, hyperlipidemia, body mass index, and smoking, the least-controlled group showed a 62% increase in the risk of cardiovascular events, compared with the SPRINT criteria group. Those who met the 2014 criteria had a 17% greater risk than those who met the SPRINT criteria.

“Despite greater cardiovascular protection with intensive BP lowering, achieving SPRINT-defined BP goals might not be easy or practical because the target BP was not met in more than one-half of the participants in the intensive-treatment group,” the authors wrote.

Individuals who were older, female, or had diabetes, chronic kidney disease, or prevalent cardiovascular disease were more likely to meet the stricter goals of SPRINT (Systolic Blood Pressure Intervention Trial), in which combined cardiovascular events occurred in 5.2% of patients treated to a target systolic blood pressure of less than 120 mm Hg and 6.8% of patients treated to a target of less than 140 mm Hg (N Engl J Med. 2015;373:2103-16).

Researchers also noted a significant linear association between lesser blood pressure control and an increased risk of myocardial infarction and stroke, although there was no significant trend seen relating to cardiovascular or all-cause mortality. The authors noted that this was the opposite to what was observed in the original SPRINT trial, where there was a reduction in cardiovascular mortality and heart failure but only a modest, nonsignificant impact on MI or stroke.

“Although the exact reasons remain unclear, this discrepancy might be explained in part by differences in study design, population characteristics, clinical practice pattern, or race or ethnic groups,” they suggested. “The generalizability of the SPRINT experience to multiple groups of various ethnic backgrounds warrants further investigations and is likely to be of considerable interest.”

Unlike the SPRINT trial, the Korean analysis did not look into the potential adverse effects of more aggressive blood pressure–lowering, but the authors noted that the SPRINT trial did see an increased incidence of more serious adverse events, including hypotension, syncope, and acute kidney injury.

“Therefore, beyond the BP target per se, several important factors should be considered for optimal BP management in the contemporary medical setting; for example, an integrated and systematic assessment of combined risk factors and baseline cardiovascular risk, concomitant preventive medical therapies, cost-effectiveness, clinician-patient discussions of the potential benefits and harms, or the clinical judgment of the treating physician.”

The National Evidence-Based Healthcare Collaborating Agency, Seoul, South Korea, funded the study. No conflicts of interest were declared.

Transcatheter aortic valve implantation shows reductions in early and mid-term all-cause mortality similar to those with surgical aortic valve replacement, even in patients with low to intermediate surgical risk, a meta-analysis and systematic review has shown.

Dr. Giuseppe Gargiulo of Federico II University in Naples, Italy, and coauthors analyzed data from five randomized trials and 31 observational matched studies comparing mortality outcomes in 16,638 patients undergoing transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (SAVR).

Their analysis found no statistically significant difference between the two procedures in terms of early or midterm all-cause mortality, even among patients judged as being at low to intermediate surgical risk (Ann Intern Med. 2016 Jun 7. doi: 10.7326/M16-0060).

In terms of 2- to 5-year mortality, overall there was a statistically nonsignificant increase in the risk of all-cause mortality with TAVI (odds ratio, 1.28; 95% confidence interval, 0.97-1.69), although the long-term mortality outcomes in patients in the low to intermediate surgical risk subgroup were inconclusive.

However, the authors did note significantly reduced early all-cause mortality in individuals who underwent transfemoral TAVI compared to those who underwent SAVR (OR 0.68, 95%CI, 0.53 to 0.87).

The analysis also showed that individuals who underwent TAVI had a higher incidence of permanent pacemaker implantation, vascular complications, and moderate to severe paravalvular leak, while those who underwent SAVR had more frequent incidence of major bleeding, acute kidney injury, and new-onset atrial fibrillation.

“These findings, which apply to adults with severe aortic stenosis, consolidate the role of TAVI as an alternative to SAVR,” the authors wrote. “Indeed, TAVI techniques continue to improve, newer valves address the issue of paravalvular leak, the percentage of pacemakers is decreasing, and the rate of vascular complications is expected to be lowered as the result of smaller sheaths and improved procedural techniques.”

The researchers noted that elderly patients and those with coronary artery disease showed a greater benefit from TAVI than from SAVR, suggesting that this may be because these groups have a heightened risk that favors less invasive surgical approaches.

They also found greater reductions in early mortality with TAVI when a Sapien valve was implanted, compared to a CoreValve. They noted that this was due mostly to a single large study and the effect did not persist through to the midterm follow-up.

One author reported grants from the CardioPath PhD Program, Federico II University of Naples, and from the European Association of Percutaneous Coronary Interventions, outside the submitted work. Another author declared a consultancy for Edwards Lifesciences. There were no other conflicts of interest declared.

Transcatheter aortic valve implantation shows reductions in early and mid-term all-cause mortality similar to those with surgical aortic valve replacement, even in patients with low to intermediate surgical risk, a meta-analysis and systematic review has shown.

Dr. Giuseppe Gargiulo of Federico II University in Naples, Italy, and coauthors analyzed data from five randomized trials and 31 observational matched studies comparing mortality outcomes in 16,638 patients undergoing transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (SAVR).

Their analysis found no statistically significant difference between the two procedures in terms of early or midterm all-cause mortality, even among patients judged as being at low to intermediate surgical risk (Ann Intern Med. 2016 Jun 7. doi: 10.7326/M16-0060).

In terms of 2- to 5-year mortality, overall there was a statistically nonsignificant increase in the risk of all-cause mortality with TAVI (odds ratio, 1.28; 95% confidence interval, 0.97-1.69), although the long-term mortality outcomes in patients in the low to intermediate surgical risk subgroup were inconclusive.

However, the authors did note significantly reduced early all-cause mortality in individuals who underwent transfemoral TAVI compared to those who underwent SAVR (OR 0.68, 95%CI, 0.53 to 0.87).

The analysis also showed that individuals who underwent TAVI had a higher incidence of permanent pacemaker implantation, vascular complications, and moderate to severe paravalvular leak, while those who underwent SAVR had more frequent incidence of major bleeding, acute kidney injury, and new-onset atrial fibrillation.

“These findings, which apply to adults with severe aortic stenosis, consolidate the role of TAVI as an alternative to SAVR,” the authors wrote. “Indeed, TAVI techniques continue to improve, newer valves address the issue of paravalvular leak, the percentage of pacemakers is decreasing, and the rate of vascular complications is expected to be lowered as the result of smaller sheaths and improved procedural techniques.”

The researchers noted that elderly patients and those with coronary artery disease showed a greater benefit from TAVI than from SAVR, suggesting that this may be because these groups have a heightened risk that favors less invasive surgical approaches.

They also found greater reductions in early mortality with TAVI when a Sapien valve was implanted, compared to a CoreValve. They noted that this was due mostly to a single large study and the effect did not persist through to the midterm follow-up.

One author reported grants from the CardioPath PhD Program, Federico II University of Naples, and from the European Association of Percutaneous Coronary Interventions, outside the submitted work. Another author declared a consultancy for Edwards Lifesciences. There were no other conflicts of interest declared.

Transcatheter aortic valve implantation shows reductions in early and mid-term all-cause mortality similar to those with surgical aortic valve replacement, even in patients with low to intermediate surgical risk, a meta-analysis and systematic review has shown.

Dr. Giuseppe Gargiulo of Federico II University in Naples, Italy, and coauthors analyzed data from five randomized trials and 31 observational matched studies comparing mortality outcomes in 16,638 patients undergoing transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (SAVR).

Their analysis found no statistically significant difference between the two procedures in terms of early or midterm all-cause mortality, even among patients judged as being at low to intermediate surgical risk (Ann Intern Med. 2016 Jun 7. doi: 10.7326/M16-0060).

In terms of 2- to 5-year mortality, overall there was a statistically nonsignificant increase in the risk of all-cause mortality with TAVI (odds ratio, 1.28; 95% confidence interval, 0.97-1.69), although the long-term mortality outcomes in patients in the low to intermediate surgical risk subgroup were inconclusive.

However, the authors did note significantly reduced early all-cause mortality in individuals who underwent transfemoral TAVI compared to those who underwent SAVR (OR 0.68, 95%CI, 0.53 to 0.87).

The analysis also showed that individuals who underwent TAVI had a higher incidence of permanent pacemaker implantation, vascular complications, and moderate to severe paravalvular leak, while those who underwent SAVR had more frequent incidence of major bleeding, acute kidney injury, and new-onset atrial fibrillation.

“These findings, which apply to adults with severe aortic stenosis, consolidate the role of TAVI as an alternative to SAVR,” the authors wrote. “Indeed, TAVI techniques continue to improve, newer valves address the issue of paravalvular leak, the percentage of pacemakers is decreasing, and the rate of vascular complications is expected to be lowered as the result of smaller sheaths and improved procedural techniques.”

The researchers noted that elderly patients and those with coronary artery disease showed a greater benefit from TAVI than from SAVR, suggesting that this may be because these groups have a heightened risk that favors less invasive surgical approaches.

They also found greater reductions in early mortality with TAVI when a Sapien valve was implanted, compared to a CoreValve. They noted that this was due mostly to a single large study and the effect did not persist through to the midterm follow-up.

One author reported grants from the CardioPath PhD Program, Federico II University of Naples, and from the European Association of Percutaneous Coronary Interventions, outside the submitted work. Another author declared a consultancy for Edwards Lifesciences. There were no other conflicts of interest declared.

Individuals with HIV and hepatitis C virus coinfection show significantly higher levels of particular inflammatory cytokines linked to liver damage, according to a study published online in HIV Medicine.

Researchers examined a range of markers of systemic inflammation in 79 HIV-infected patients – 42 of whom were coinfected with hepatitis C – and all of whom had been on antiretroviral therapy and had plasma viral levels suppressed below 50 HIV-1 RNA copies per ml, and compared them to 20 healthy controls.

©grandeduc/Thinkstock

Their analysis initially revealed that the individuals with HIV/HCV coinfection had higher plasma levels of interleukin-6, interferon gamma-induced protein (IP)-10, monocyte/macrophage markers neopterin and sCD163, and soluble tumour necrosis factor receptor-II than individuals with HIV infection alone.

However after adjusting for duration of HIV infection and gender, researchers only found a significant difference between HIV/HCV coinfected individuals and those with HIV alone in plasma levels of IP-10, sCD163 and neopterin (HIV Medicine. 2016 May 17. doi:10.1111/hiv.12357).

The study also undertook to correlate these markers with hepatic damage, and found a highly significant and consistent relationship between aspartate aminotransferase, alanine aminotransferase and AST-to platelet-ratio index, and plasma IP-10, sCD163 and neopterin.

“Although a contribution of ART-induced hepatotoxicity in the setting of HCV/HIV coinfection cannot be excluded, a simpler and more plausible explanation is that the observed effects are related to HCV/HIV-mediated liver damage,” wrote Dr. Konstantin V. Shmagel, from the Institute of Ecology and Genetics of Microorganisms at the Russian Academy of Sciences in Perm, Russia.

“The relationship among these indices remains incompletely understood but it is possible that processes taking place in the liver may play a role in alteration of CD4 T-cell recovery during ART in the setting of HCV/HIV coinfection.”

The analysis also showed the inflammatory markers IL-6, neopterin and sCD14 were also elevated – although not to the same degree – in individuals with HIV monoinfection compared to the healthy controls.

“The drivers of persistent inflammation in treated HIV infection and HIV/HCV coinfection are not entirely clear but, in these settings, damage to the gut epithelial barrier has been implicated in promoting translocation of microbial products from the gut lumen into the systemic circulation,” the authors wrote.

This study was supported by the National Institute of Allergy and Infectious Diseases, the Center for AIDS Research at Case Western Reserve University, and the Russian Science Foundation. No conflicts of interest were declared.

Individuals with HIV and hepatitis C virus coinfection show significantly higher levels of particular inflammatory cytokines linked to liver damage, according to a study published online in HIV Medicine.

Researchers examined a range of markers of systemic inflammation in 79 HIV-infected patients – 42 of whom were coinfected with hepatitis C – and all of whom had been on antiretroviral therapy and had plasma viral levels suppressed below 50 HIV-1 RNA copies per ml, and compared them to 20 healthy controls.

©grandeduc/Thinkstock

Their analysis initially revealed that the individuals with HIV/HCV coinfection had higher plasma levels of interleukin-6, interferon gamma-induced protein (IP)-10, monocyte/macrophage markers neopterin and sCD163, and soluble tumour necrosis factor receptor-II than individuals with HIV infection alone.

However after adjusting for duration of HIV infection and gender, researchers only found a significant difference between HIV/HCV coinfected individuals and those with HIV alone in plasma levels of IP-10, sCD163 and neopterin (HIV Medicine. 2016 May 17. doi:10.1111/hiv.12357).

The study also undertook to correlate these markers with hepatic damage, and found a highly significant and consistent relationship between aspartate aminotransferase, alanine aminotransferase and AST-to platelet-ratio index, and plasma IP-10, sCD163 and neopterin.

“Although a contribution of ART-induced hepatotoxicity in the setting of HCV/HIV coinfection cannot be excluded, a simpler and more plausible explanation is that the observed effects are related to HCV/HIV-mediated liver damage,” wrote Dr. Konstantin V. Shmagel, from the Institute of Ecology and Genetics of Microorganisms at the Russian Academy of Sciences in Perm, Russia.

“The relationship among these indices remains incompletely understood but it is possible that processes taking place in the liver may play a role in alteration of CD4 T-cell recovery during ART in the setting of HCV/HIV coinfection.”

The analysis also showed the inflammatory markers IL-6, neopterin and sCD14 were also elevated – although not to the same degree – in individuals with HIV monoinfection compared to the healthy controls.

“The drivers of persistent inflammation in treated HIV infection and HIV/HCV coinfection are not entirely clear but, in these settings, damage to the gut epithelial barrier has been implicated in promoting translocation of microbial products from the gut lumen into the systemic circulation,” the authors wrote.

This study was supported by the National Institute of Allergy and Infectious Diseases, the Center for AIDS Research at Case Western Reserve University, and the Russian Science Foundation. No conflicts of interest were declared.

Individuals with HIV and hepatitis C virus coinfection show significantly higher levels of particular inflammatory cytokines linked to liver damage, according to a study published online in HIV Medicine.

Researchers examined a range of markers of systemic inflammation in 79 HIV-infected patients – 42 of whom were coinfected with hepatitis C – and all of whom had been on antiretroviral therapy and had plasma viral levels suppressed below 50 HIV-1 RNA copies per ml, and compared them to 20 healthy controls.

©grandeduc/Thinkstock

Their analysis initially revealed that the individuals with HIV/HCV coinfection had higher plasma levels of interleukin-6, interferon gamma-induced protein (IP)-10, monocyte/macrophage markers neopterin and sCD163, and soluble tumour necrosis factor receptor-II than individuals with HIV infection alone.

However after adjusting for duration of HIV infection and gender, researchers only found a significant difference between HIV/HCV coinfected individuals and those with HIV alone in plasma levels of IP-10, sCD163 and neopterin (HIV Medicine. 2016 May 17. doi:10.1111/hiv.12357).

The study also undertook to correlate these markers with hepatic damage, and found a highly significant and consistent relationship between aspartate aminotransferase, alanine aminotransferase and AST-to platelet-ratio index, and plasma IP-10, sCD163 and neopterin.

“Although a contribution of ART-induced hepatotoxicity in the setting of HCV/HIV coinfection cannot be excluded, a simpler and more plausible explanation is that the observed effects are related to HCV/HIV-mediated liver damage,” wrote Dr. Konstantin V. Shmagel, from the Institute of Ecology and Genetics of Microorganisms at the Russian Academy of Sciences in Perm, Russia.

“The relationship among these indices remains incompletely understood but it is possible that processes taking place in the liver may play a role in alteration of CD4 T-cell recovery during ART in the setting of HCV/HIV coinfection.”

The analysis also showed the inflammatory markers IL-6, neopterin and sCD14 were also elevated – although not to the same degree – in individuals with HIV monoinfection compared to the healthy controls.

“The drivers of persistent inflammation in treated HIV infection and HIV/HCV coinfection are not entirely clear but, in these settings, damage to the gut epithelial barrier has been implicated in promoting translocation of microbial products from the gut lumen into the systemic circulation,” the authors wrote.

This study was supported by the National Institute of Allergy and Infectious Diseases, the Center for AIDS Research at Case Western Reserve University, and the Russian Science Foundation. No conflicts of interest were declared.

As many as one-third of healthy first-degree relatives of individuals with ankylosing spondylitis may meet the criteria for spondyloarthritis, according to results from a prospective cohort study.

Dr. Maureen C. Turina of the Amsterdam Rheumatology and Immunology Center at the University of Amsterdam and her coauthors enrolled 51 first-degree relatives of individuals with HLA-B27–positive ankylosing spondylitis in the study to see whether any of these otherwise healthy individuals showed early signs of the disease. They found that 17 (33%) of these first-degree relatives fulfilled any of the spondyloarthritis (SpA) classification criteria at baseline – a higher rate than reported in previous studies – and 7 (14%) met both the Assessment of Spondyloarthritis International Society (ASAS) criteria and European Spondyloarthropathy Study Group (ESSG) criteria.

©Rocky89/Thinkstock.com

The authors suggested that the higher rate, compared with previous studies, could be due to channeling bias, as individuals with clinical symptoms may have been more willing to participate in the study.

However, 4 of the 38 individuals who did not fulfill either of these criteria for SpA still showed imaging abnormalities – including syndesmophytes on the cervical spine and bone marrow edema in the sacroiliac joint.

The authors suggested these imaging abnormalities may represent a subclinical phase of SpA (Arthritis Rheumatol. 2016 May 23. doi: 10.1002/art.39766).

The participants who met the ASAS and/or ESSG classification criteria for SpA had more axial, entheseal, and joint pain, compared with those who did not meet the criteria. All of these patients also reported back pain, compared with 35% of those who did not fulfill the criteria.

However, the individuals meeting the SpA criteria had low overall disease scores, and did not show any increase in inflammatory serum markers.

“Importantly, some key features of SpA including the presence of peripheral disease or extra-articular manifestations and increased inflammatory parameters were only rarely observed in FDRs [first-degree relatives] and were also not different in those fulfilling the ASAS axSpA and/or ESSG classification criteria versus those who did not,” the authors reported.

“Future follow-up will learn if and which of these FDRs will evolve into the clinically established phase of SpA.”

When specifically asked, more than half (57%) of the first-degree relatives said they had back pain, and 40% said they had experienced or were experiencing arthralgia.

“The fact that these FDRs were not investigated for or diagnosed with axial SpA before inclusion in the study may be related either to the fact that the back pain symptoms were relatively mild or to ignorance of general physicians for these alarm symptoms,” the authors wrote.

One person said they had past or present peripheral arthritis but none reported enthesitis or dactylitis.

While none of the subjects had arthritis, 16% reported at least one tender joint, and 22% had a modified Schober score of less than 4.5 cm, with 4% showing a chest expansion of less than 3.6 cm.

Researchers also examined whether HLA-B27 status had any impact on the first-degree relatives, as previous studies had suggested that SpA is more likely to present in HLA-B27–positive first-degree relatives.

However they found no differences between the HLA-B27–positive and HLA-B27–negative groups in terms of demographics, symptom history, disease activity, clinical examination, or laboratory or imaging data; a finding the authors described as “intriguing.”

“However, if confirmed in a larger sample set, further follow-up of these FDRs will allow us to determine if FDRs showing signs and symptoms of SpA will evolve to more active and severe disease, independently of HLA-B27 status or, alternatively, if the presence of HLA-B27 may promote exacerbation and persistence of subclinical pathology.”

The study was supported by the Dutch Arthritis Foundation. No conflicts of interest were declared.

As many as one-third of healthy first-degree relatives of individuals with ankylosing spondylitis may meet the criteria for spondyloarthritis, according to results from a prospective cohort study.

Dr. Maureen C. Turina of the Amsterdam Rheumatology and Immunology Center at the University of Amsterdam and her coauthors enrolled 51 first-degree relatives of individuals with HLA-B27–positive ankylosing spondylitis in the study to see whether any of these otherwise healthy individuals showed early signs of the disease. They found that 17 (33%) of these first-degree relatives fulfilled any of the spondyloarthritis (SpA) classification criteria at baseline – a higher rate than reported in previous studies – and 7 (14%) met both the Assessment of Spondyloarthritis International Society (ASAS) criteria and European Spondyloarthropathy Study Group (ESSG) criteria.

©Rocky89/Thinkstock.com

The authors suggested that the higher rate, compared with previous studies, could be due to channeling bias, as individuals with clinical symptoms may have been more willing to participate in the study.

However, 4 of the 38 individuals who did not fulfill either of these criteria for SpA still showed imaging abnormalities – including syndesmophytes on the cervical spine and bone marrow edema in the sacroiliac joint.

The authors suggested these imaging abnormalities may represent a subclinical phase of SpA (Arthritis Rheumatol. 2016 May 23. doi: 10.1002/art.39766).

The participants who met the ASAS and/or ESSG classification criteria for SpA had more axial, entheseal, and joint pain, compared with those who did not meet the criteria. All of these patients also reported back pain, compared with 35% of those who did not fulfill the criteria.

However, the individuals meeting the SpA criteria had low overall disease scores, and did not show any increase in inflammatory serum markers.

“Importantly, some key features of SpA including the presence of peripheral disease or extra-articular manifestations and increased inflammatory parameters were only rarely observed in FDRs [first-degree relatives] and were also not different in those fulfilling the ASAS axSpA and/or ESSG classification criteria versus those who did not,” the authors reported.

“Future follow-up will learn if and which of these FDRs will evolve into the clinically established phase of SpA.”

When specifically asked, more than half (57%) of the first-degree relatives said they had back pain, and 40% said they had experienced or were experiencing arthralgia.

“The fact that these FDRs were not investigated for or diagnosed with axial SpA before inclusion in the study may be related either to the fact that the back pain symptoms were relatively mild or to ignorance of general physicians for these alarm symptoms,” the authors wrote.

One person said they had past or present peripheral arthritis but none reported enthesitis or dactylitis.

While none of the subjects had arthritis, 16% reported at least one tender joint, and 22% had a modified Schober score of less than 4.5 cm, with 4% showing a chest expansion of less than 3.6 cm.

Researchers also examined whether HLA-B27 status had any impact on the first-degree relatives, as previous studies had suggested that SpA is more likely to present in HLA-B27–positive first-degree relatives.

However they found no differences between the HLA-B27–positive and HLA-B27–negative groups in terms of demographics, symptom history, disease activity, clinical examination, or laboratory or imaging data; a finding the authors described as “intriguing.”

“However, if confirmed in a larger sample set, further follow-up of these FDRs will allow us to determine if FDRs showing signs and symptoms of SpA will evolve to more active and severe disease, independently of HLA-B27 status or, alternatively, if the presence of HLA-B27 may promote exacerbation and persistence of subclinical pathology.”

The study was supported by the Dutch Arthritis Foundation. No conflicts of interest were declared.

As many as one-third of healthy first-degree relatives of individuals with ankylosing spondylitis may meet the criteria for spondyloarthritis, according to results from a prospective cohort study.

Dr. Maureen C. Turina of the Amsterdam Rheumatology and Immunology Center at the University of Amsterdam and her coauthors enrolled 51 first-degree relatives of individuals with HLA-B27–positive ankylosing spondylitis in the study to see whether any of these otherwise healthy individuals showed early signs of the disease. They found that 17 (33%) of these first-degree relatives fulfilled any of the spondyloarthritis (SpA) classification criteria at baseline – a higher rate than reported in previous studies – and 7 (14%) met both the Assessment of Spondyloarthritis International Society (ASAS) criteria and European Spondyloarthropathy Study Group (ESSG) criteria.

©Rocky89/Thinkstock.com

The authors suggested that the higher rate, compared with previous studies, could be due to channeling bias, as individuals with clinical symptoms may have been more willing to participate in the study.

However, 4 of the 38 individuals who did not fulfill either of these criteria for SpA still showed imaging abnormalities – including syndesmophytes on the cervical spine and bone marrow edema in the sacroiliac joint.

The authors suggested these imaging abnormalities may represent a subclinical phase of SpA (Arthritis Rheumatol. 2016 May 23. doi: 10.1002/art.39766).

The participants who met the ASAS and/or ESSG classification criteria for SpA had more axial, entheseal, and joint pain, compared with those who did not meet the criteria. All of these patients also reported back pain, compared with 35% of those who did not fulfill the criteria.

However, the individuals meeting the SpA criteria had low overall disease scores, and did not show any increase in inflammatory serum markers.

“Importantly, some key features of SpA including the presence of peripheral disease or extra-articular manifestations and increased inflammatory parameters were only rarely observed in FDRs [first-degree relatives] and were also not different in those fulfilling the ASAS axSpA and/or ESSG classification criteria versus those who did not,” the authors reported.

“Future follow-up will learn if and which of these FDRs will evolve into the clinically established phase of SpA.”

When specifically asked, more than half (57%) of the first-degree relatives said they had back pain, and 40% said they had experienced or were experiencing arthralgia.

“The fact that these FDRs were not investigated for or diagnosed with axial SpA before inclusion in the study may be related either to the fact that the back pain symptoms were relatively mild or to ignorance of general physicians for these alarm symptoms,” the authors wrote.

One person said they had past or present peripheral arthritis but none reported enthesitis or dactylitis.

While none of the subjects had arthritis, 16% reported at least one tender joint, and 22% had a modified Schober score of less than 4.5 cm, with 4% showing a chest expansion of less than 3.6 cm.

Researchers also examined whether HLA-B27 status had any impact on the first-degree relatives, as previous studies had suggested that SpA is more likely to present in HLA-B27–positive first-degree relatives.

However they found no differences between the HLA-B27–positive and HLA-B27–negative groups in terms of demographics, symptom history, disease activity, clinical examination, or laboratory or imaging data; a finding the authors described as “intriguing.”

“However, if confirmed in a larger sample set, further follow-up of these FDRs will allow us to determine if FDRs showing signs and symptoms of SpA will evolve to more active and severe disease, independently of HLA-B27 status or, alternatively, if the presence of HLA-B27 may promote exacerbation and persistence of subclinical pathology.”

The study was supported by the Dutch Arthritis Foundation. No conflicts of interest were declared.