Central Hearing Loss May Affect Memory

Central Hearing Loss May Affect Memory

In contrast to age-related hearing loss, central hearing loss may share the same mechanism of neurodegeneration with cognitive decline, new research suggests.

The study showed that patients with central hearing loss, or central presbycusis, were twice as likely to have mild cognitive impairment (MCI) as those with no hearing loss, but there was no association between age-related hearing loss, or peripheral presbycusis, and cognitive impairment.

“Preventing hearing impairment with hearing aids early on could greatly reduce or delay the onset of cognitive neurodegeneration,” lead author, Rodolfo Sardone, AuD, EngD, MPh, research coordinator, The Great Age Study, National Institute of Health and University of Bari, Italy, told Medscape Medical News.

“To do this, we need to improve the assessment of hearing, improve hearing aids fitting, and decrease their costs.”

The study will be presented at the American Academy of Neurology (AAN) 2018 Annual Meeting in Los Angeles, California.

Central Deficit

An estimated one third of the elderly population worldwide has a disabling hearing loss. Many have peripheral presbycusis, which is caused by malfunctions of the inner ear or nerves.

Others may have central presbycusis, where the hearing threshold, as measured by tonal audiometry, is normal and therefore the cochlea is presumably intact.

“The central deficit manifests only in situations of competitive signals like another speaker or background noise,” explained Sardone. “It is a deficit linked to hearing perception rather than to hearing sensation.”

Mounting evidence supports a link between presbycusis and cognitive decline, but few studies have investigated the role of peripheral vs central presbycusis in MCI.

The Great Age Study is an ongoing population-based study on aging conducted in southern Italy. The study’s principal investigator is Giancarlo Logroscino, MD, PhD, director of the Neurodegenerative Diseases Unit and associate professor of neurology, University of Bari.

The current analysis included 1604 participants, mean age 73.7 years. Participants underwent numerous assessments, including neurologic, neuropsychological, and otolaryngology assessments.

Cognitive Assessment

To assess cognition, researchers used Petersen criteria (2004) for MCI. They targeted MCI, said Sardone, because “it’s considered a preclinical phase of dementia, and we’re interested in exploring the onset of neurodegeneration.”

All neurologic assessments were carried out by a clinical neuropsychologist and validated by a neurologist, said Sardone. 

Peripheral and central presbycusis were identified by using Gates (2012) criteria, he said.

Peripheral hearing loss was an average pure tone audiometry (PTA) of 40 decibels hearing level (dBHL) or greater.

Central hearing loss was identified in participants with normal hearing threshold (<40 dBHL) who had difficulty hearing amid noise, as assessed by using the ipsilateral competitive message test.

Of the total study participants, 25.5% had peripheral presbycusis and 12.1% had central presbycusis.

This percentage of central hearing loss is “in line with” findings of other studies, including cohorts of the Framingham Heart Study, said Sardone.

About a third (33%) of study participants were diagnosed with MCI.

The analysis showed that compared with those with no hearing loss, participants with central presbycusis were at increased risk for MCI (odds ratio, 2.1, P < .0001).

The study found no association between peripheral presbycusis and cognitive impairment.

Of the 1604 participants in the study, 769 were male. There were no statistically significant differences in results between men and women.

The results suggest that central presbycusis may share the same progressive loss of functioning in brain cells that occurs in cognitive decline, rather than the sensory deprivation that happens with peripheral presbycusis, said Sardone.

Speech Discrimination

The researchers also looked at speech discrimination, or the ability to understand words at certain sound intensities.

Speech discrimination is assessed by using speech audiometry, using a score that ranges from 0% (worst) to 100% (best). The score is the number of words that a person is able to repeat from a list of 10, at an intensity higher than that of the person’s PTA, explained Sardone.

For this analysis, the cutoff for speech discrimination impairment was a percentage of repeated words less than 70% in the best ear at an intensity greater than 40 dBHL above its auditory threshold (PTA) in that ear, he said.

They found a positive correlation between the average speech discrimination score and the Mini-Mental State Examination (MMSE) score (P < .0001).

“We found that higher values ​​of speech discrimination correlate with higher values ​​of MMSE,” said Sardone. “Those who understand the words better have a better global cognitive function.”

Two possible hypotheses might explain the link between central presbycusis and MCI, said Sardone. The first is mechanistic — sensory deprivation leads to weakening of the neural structures of the brainstem and the temporal cortex.

This, he said, reflects the well-known neuroscientific concept of “use it or lose it.”

Another explanation is that hearing impairment starts with vascular degeneration, or some other common cause of neurodegeneration.

“This hypothesis better explains the presence of neuropathological changes, and the presence of speech discrimination disorders even in the absence of peripheral cochlear damage,” said Sardone.

All patients aged 65 years and older should have a hearing test once a year, said Sardone. He recommends that anyone who has difficulty understanding words, has concerns about memory, or has documented cognitive deficits should be tested, too.

Important Implications

Asked to comment, Pinky Agarwal, MD, Evergreen Health, Kirkland, Washington, professor of neurology, University of Washington, and a fellow of the American Academy of Neurology, said the study could have important implications for healthcare and for public policy.

She noted that while about 29% of the US population aged 60 to 69 years has hearing impairment, this increases to 63% among those aged 70 years or over.

Agarwal also pointed to the “high possibility” that cognitive impairment will progress to dementia.

“Prevention of cognitive impairment and dementia has become a public health priority due to its irreversibility and its burden upon individuals, families, and society.”

The current study tries to demonstrate the association between categories of hearing loss and cognitive impairment, but more research is warranted to provide additional insight, said Agarwal. 

“Further studies should be conducted to generate conclusive evidence to elicit the causal link between cognitive impairment and hearing loss after controlling for variables such as age, gender, race, education, presence of diabetes, smoking history, and hypertension.”

And more research is needed to examine implications of environmental factors, such as loss of ability to communicate, social isolation, and cognitive impairment, among patients with central hearing loss, said Agarwal. 

“If a causal relationship is established, screening for central hearing including speech discrimination may be added to annual wellness examinations.”

 The study was supported by the Italian Ministry of Health and the Puglia Regional Government. Sardone and Agarwal have disclosed no relevant financial relationships.

American Academy of Neurology (AAN) 2018 Annual Meeting. Abstract 2928 (P2.179). To be presented April 23, 2018.

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Firearm-related Injuries Drop During NRA Conventions

Firearm-related Injuries Drop During NRA Conventions

(Reuters Health) – Gunshot-related deaths and injuries temporarily show a dramatic decline when the National Rifle Association is holding its annual convention, according to a new analysis online February 28 in The New England Journal of Medicine.

The authors say it’s evidence that firearms – even in the hands of experienced users – are inherently dangerous and accidents don’t just happen among novices.

Dr. Anupam Jena of Harvard Medical School and Andrew Olenski of Columbia University compared firearm injuries during the conventions each year from 2007 through 2015 with injury rates three weeks before and three weeks after each event.

A decline of 63% was seen in the states where the conventions were being held, apparently due to large numbers of gun owners being at the events, as well as, in some cases, gun venues such as firing ranges or hunting grounds having closed while their staff attended the convention.

Nationally, there was a 20% reduction in firearm injuries during the convention.

In contrast, gun-related crime did not decrease during the conventions.

The drop in injuries was only seen among men. It was most prominent in the states with the highest rate of gun ownership, and among people living in the South and the West.

“These findings are consistent with reductions in firearm injuries occurring as a result of lower rates of firearm use during the brief period when many firearm owners and owners of places where firearms are used may be attending an NRA convention,” they said. “Our results suggest that firearm-safety concerns and risks of injury are relevant even among experienced gun owners.”

The NRA did not immediately respond to a request for comment.

The study comes at a time when Americans own an estimated 265 million to 300 million guns, which is about one for every adult. Thirty percent of Americans say they own at least one gun, and another 11% say they live in a household with someone who owns one, according to the Pew Research Center. In 2014, 461 people died from an accidental firearm discharge and 15,928 were injured, nearly 2,000 of whom were children, the study authors note.

“This passes the sniff test. It makes sense that decreased exposure and decreased usage would result in fewer events,” said Dr. Stephen Hargarten, chairman of emergency medicine at the Medical College of Wisconsin, in Milwaukee, who was not involved in the study.

“I have worked with lifetime members of the NRA who secretly confess that they have unintended discharges of their rifles or shotguns. And this study doesn’t account for the unintended discharges that didn’t result in injury,” he told Reuters Health in a telephone interview.

“We’re saying, ‘Here’s a brief period of time when people likely to use guns are not using them,'” and the injury rates go down, Jena told Reuters Health by phone.

The researchers used an insurance database to track firearm injuries during conventions in Nashville, Indianapolis, Houston, St. Louis, Pittsburgh, Charlotte, Phoenix, Louisville and St. Louis.

Nationally, the rate of firearm injury dropped from 1.5 per 100,000 on the dates adjacent to the convention to 1.2 per 100,000 during the convention itself. And in the state where the convention was held, the injury rate went from 1.9 down to 0.7 per 100,000.

With as many as 80,000 firearm owners attending a convention, “the relationship is not just possibly due to 80,000 members not using firearms as much during the date of the convention,” Jena said. “It could be that firing ranges and hunting grounds are more likely to be closed. There could be a larger network effect that could be at play here.”

It’s also relevant that the effect is largest in states that hold a meeting in a given year, he noted. “If the convention is closer to you in a given year, the effect should be larger, and we find that.”

During the NRA’s Atlanta convention in 2017, 60% of the 81,000 NRA members traveled more than 200 miles to attend, according to the organization’s 2018 convention website.

“I think the most sophisticated and reasoned gun supporters will not be surprised by this,” Jena said. “All we are saying is that guns are inherently unsafe and you recognize that whenever you use a firearm. Even an experienced user may still suffer from a gun-related injury. That’s like saying even the best drivers in the world may still get in a car accident. Why? Because driving is inherently an unsafe activity compared to walking around in circles in your house.”

It would seem reasonable to investigate ways to make guns safer, Hargarten said. “We’ve integrated safety features into other products, but there has not been a collective discussion about this product, as we had with cars in the 1960s.”

SOURCE: http://bit.ly/2CKXQfa

N Engl J Med 2018.

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Vaping May Help Pneumonia-causing Bacteria Invade Airways

Vaping May Help Pneumonia-causing Bacteria Invade Airways

(Reuters Health) – People who smoke e-cigarettes might have an increased risk of developing pneumonia because the vapor could help bacteria stick to cells lining the airways, a small experiment suggests.

Traditional cigarettes have long been linked to an increased risk of pneumonia, but it’s been less clear whether e-cigarettes might have the same effect.

To find out, researchers did a series of laboratory experiments to see whether exposure to e-cigarette vapor might increase levels of a molecule produced by airway lining cells, called platelet-activating factor receptor (PAFR).

Pneumococcal bacteria use PAFR to help them adhere to airway cells.

First, the researchers exposed some human airway epithelial cells in culture dishes to e-cigarette vapor. Compared to cells that weren’t exposed, those that were had PAFR levels three times higher.

Then, they exposed mice to e-cigarette vapor and found higher PAFR production in the rodents who inhaled the fumes.

Finally, the researchers asked 17 people who were regular vapers to come smoke an e-cigarette in the lab. Compared with these participants’ PAFR levels measured before the vaping session, there was a three-fold increase in PAFR levels an hour after people smoked e-cigarettes.

“The take-home message is that it is over-optimistic to assume that all of the adverse effects of cigarette smoking are reduced by switching to vaping,” said senior study author Jonathan Grigg of Queen Mary University of London.

“It also raises the question that, even if we have not proved that vaping increases the risk of pneumonia, for young people taking up vaping for the first time, a precautionary approach would suggest that the risk should be assumed to exist until proved otherwise,” Grigg said by email.

Big U.S. tobacco companies are all developing e-cigarettes. The battery-powered gadgets feature a glowing tip and a heating element that turns liquid nicotine and flavorings into a cloud of vapor that users inhale.

Even when e-liquids don’t contain nicotine, the lungs are still exposed to flavoring chemicals when the e-liquids are heated and the vapors are inhaled.

Some previous research, mostly in lab experiments, has linked exposure to these flavorings to an increase in biomarkers for inflammation and tissue damage. This type of cell damage can lead to lung problems including fibrosis, chronic obstructive pulmonary disorder and asthma.

In the current lab experiment, PAFR levels surged in human nose lining cells in culture dishes exposed to e-liquids with nicotine and in cells exposed to nicotine-free vapor. This was accompanied by increased adhesion by pneumonia-causing bacteria.

Even though the study is small and the results must be verified in larger human trials, the findings still suggest that e-cigarettes aren’t risk-free and shouldn’t necessarily be considered a safe way for people to try to curb use of traditional cigarettes, the researchers conclude online February 7 in the European Respiratory Journal.

At least when it comes to pneumonia, nicotine patches or gum may be a safer option for smoking cessation, the researchers note.

“PAFR expression is enhanced in cigarette smokers and patients with chronic obstructive pulmonary disorder and has been hypothesized to be mediating enhanced adhesion of bacteria to epithelial cells and subsequent development of pneumonia,” said Ilona Jaspers, deputy director of the Center for Environmental Medicine, Asthma & Lung Biology at the University of North Carolina at Chapel Hill.

“The data shown here suggest that vaping e-cigarettes could also increase expression of PAFR in relevant epithelial cells,” Jaspers, who wasn’t involved in the study, said by email. “In general, I would refrain from calling e-cigarettes ‘safer’ than cigarettes, but would suggest calling them causing ‘different’ effects than cigarettes.”

SOURCE: http://bit.ly/2nV3Ts7

Eur Respir J 2018.

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Calcium Supplements Up Risk for Precancerous Serrated Polyps

Calcium Supplements Up Risk for Precancerous Serrated Polyps

Researchers thought calcium supplementation might reduce development of precancerous colorectal polyps. It didn’t.

Calcium supplementation alone more than doubled the risk for serrated sessile adenomas or polyps (SSA/Ps), and when combined with vitamin D, it almost quadrupled the risk, according to the results of a large randomized chemoprevention trial published online today in Gut.

Earlier research had suggested that people with high dietary calcium intake are at lower risk for polyps, including the serrated type. “So it stands to reason that calcium supplementation could have beneficial effects in terms of preventing colon cancer or polyps,” lead author Seth D. Crockett, MD, from the University of North Carolina’s Division of Gastroenterology and Hepatology in Chapel Hill, told Medscape Medical News.

“But, in contrast, we found evidence that calcium supplementation appeared to be associated with a risk of precancerous serrated polyps.” He noted, however, that neither dietary calcium nor vitamin D supplements alone appear to increase risk.

Between 2005 and 2008, Crockett and colleagues enrolled 2259 participants, 45 to 75 years of age, from 11 US academic centers in the US Vitamin D/Calcium Polyp Prevention Study. All patients had had at least one adenoma removed during a baseline colonoscopy and were randomly assigned to four main treatment groups: 1200 mg/day of elemental calcium carbonate plus placebo (n = 419), 1000 IU/day of vitamin D³ plus placebo (n = 420), calcium plus vitamin D (n = 421), or placebo (n = 415). Women unwilling to discontinue calcium supplements were randomly assigned to a calcium-plus-placebo (n = 295) group or a calcium-plus-vitamin D group (n = 289).

After 3 or 5 years of supplementation (treatment phase), patients underwent a colonoscopy and were assessed again 3 to 5 years after stopping supplementation (observation phase).

During the treatment phase, researchers diagnosed serrated polyps in 565 (27.5%) of 2058 evaluable participants. There were 1111 serrated polyps, including 955 hyperplastic polyps and 132 SSA/Ps.

In the observation phase, investigators diagnosed serrated polyps among 329 (29.7%) of 1108 participants who underwent a colonoscopy. There were 607 serrated polyps, including 498 hyperplastic polyps and 79 SSA/Ps.

When analyzed by type of supplementation, the authors found no statistically significant differences in risk for serrated polyps, hyperplastic polyps, or SSA/Ps during the treatment phase.

However, risk differences were apparent during the observation phase for SSA/Ps, but not for serrated polyps or hyperplastic polyps. Specifically, the adjusted risk ratio (aRR) for SSA/Ps among patients randomly assigned to calcium alone was 2.65 (95% confidence interval [CI], 1.43 – 4.91) vs placebo, and for those taking combined calcium and vitamin D, it was 3.81 (95% CI, 1.25 – 11.64).

The risks were greatest for women and current smokers. Although nonsmokers had a calcium-associated aRR for any serrated polyp of 1.04 (95% CI, 0.87 – 1.24), current smokers had an aRR of 2.16 (95% CI, 1.32 – 3.51; P interaction = .02). In women, calcium was associated with a higher risk for serrated polyps overall (aRR, 2.62; 95% CI, 1.39 – 4.95; P for trend = .004), and specifically of hyperplastic polyps (aRR, 2.50; 95% CI, 1.22 – 5.13; P for trend = .004).

Crockett and associates conclude that although risks should be always weighed against benefits, patients with a history of premalignant sessile polyps, particularly women and smokers, might consider avoiding these supplements.

Supplements had no effect on the development of conventional adenomas, which is consistent with earlier data reported from the same trial.

These new findings are cause for concern, as serrated polyps are precursors to 20% to 30% of sporadic cases of colorectal cancer and need to be targeted along with conventional adenomas, the authors note. “Further studies are recommended to confirm these results, which may have important implications for [colorectal cancer] screening and prevention,” they write.

In the meantime, should supplement users take any action in light of these results? “It’s important to put these findings in perspective and not to cause alarm as calcium and vitamin D supplements are taken by lots of people and have many beneficial effects,” Crockett said. “The possible association we found does not necessarily negate the other benefits.”

However, for people such as smokers and those with a history of serrated polyps, the findings could alter the balance of risks and benefits of calcium supplementation. “And people need to keep their regular screening and colonoscopies up to date,” he adds.

This study was funded by a grant from the National Institutes of Health, National Cancer Institute. Lead author Crockett was supported in part by a grant from the National Institutes of Health. The authors have disclosed no competing interests related to this article, but several reported ties to industry outside this work.

Gut. Published online March 1, 2018.

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Costs of Supplemental Donor Human Milk on Par With Formula for Preemies

Costs of Supplemental Donor Human Milk on Par With Formula for Preemies

NEW YORK (Reuters Health) – For very-low-birth-weight (VLBW) infants, the cost of supplemental donor human milk (DHM) is about the same as preterm formula, according to a cost-effectiveness analysis of a Canadian study.

Compared with formula, supplemental DHM is associated with a lower incidence of necrotizing enterocolitis (NEC) in VLBW infants, but until now, the cost-effectiveness of DHM in this population from a societal perspective up to 18 months’ corrected age was unknown.

Dr. Deborah O’Connor from the University of Toronto and colleagues looked at this issue in the Donor Milk for Improved Neurodevelopmental Outcomes study – a double-blind, randomized controlled trial that enrolled 363 VLBW infants (mean birth weight, 996 grams) from tertiary neonatal ICUs in southern Ontario.

The main results from the study, reported in JAMA in 2016 (http://bit.ly/2ox9cPm), showed that VLBW infants fed fortified DHM as a supplement to maternal milk had neurodevelopmental outcomes similar to those of their peers supplemented with formula. A preplanned analysis found a lower incidence of any-stage NEC in the DHM group (3.9% vs. 11.0%; P=0.01).

The cost-effectiveness analysis, reported online February 28 in Pediatrics, found similar average total costs out to 18 months’ corrected age of supplementing with DHM and preterm formula. The average costs in 2015 Canadian dollars were $217,624 and $217,245, respectively.

“In fact, we found some evidence that total costs after hospital discharge were less in infants supplemented with donor milk,” Dr. O’Connor told Reuters Health by email.

The researchers calculate that DHM cost an additional $5,328 (2015 Canadian dollars) per case of NEC averted by providing supplemental DHM. They caution, however, that there is “broad uncertainty” about this estimate. Nonetheless, Dr. O’Connor said, “given the short- and long-term sequelae associated with NEC and data presented in our study suggesting no difference in costs during initial hospitalization and potential cost-saving after discharge, use of supplemental donor milk over preterm formula is warranted.”

“This is the first prospective cost-effectiveness analysis of DHM alongside a blinded RCT, and involved comprehensive analysis of infant-level costs,” the researchers note in their article. “This experimental approach to health policy minimizes bias, optimizes internal validity, and permits simultaneous consideration of actual cost and effect distributions without the assumptions inherent in modeling studies. Moreover, unlike most formal economic evaluations in the neonatal trial literature, this analysis took a societal perspective, in which an attempt was made to capture all costs related to preterm birth to 18 months’ corrected age, including parental out-of-pocket expenses.”

The fact that the study was done in a single urban Canadian area is a limitation and might preclude generalizing the results to other settings in which mother’s milk feeding or costs might differ.

“Canada and the U.S. share many similar approaches to caring for very-low-birth-weight infants, but our health care systems do differ. Nonetheless, the main conclusion, that donor milk is economically justifiable for very-low-birth-weight infants, would be expected to hold in the U.S. as well,” Dr. O’Connor told Reuters Health.

The study had no commercial funding, and the authors disclosed no conflicts of interest.

SOURCE: http://bit.ly/2CpZoPP

Pediatrics 2018.

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FDA Committee Recommends 2018-2019 Influenza Vaccine Strains

FDA Committee Recommends 2018-2019 Influenza Vaccine Strains

The US Food and Drug Administration’s (FDA’s) Vaccines and Related Biological Products Advisory Committee has chosen the influenza vaccine strains for the 2018-2019 season in the Northern Hemisphere, which begins in the fall of 2018.

On February 22, the World Health Organization made its recommendations as to which influenza strains to include in vaccines for the coming influenza season. The committee voted on those recommendations today.

Overall vaccine effectiveness against influenza A(H3N2) — the predominant strain of influenza this season — has been 25% as of February 15.

FDA Commissioner Scott Gottlieb, MD, said in a February 26 news release that he believes the influenza A(H3N2) virus strain selected for this season’s vaccine was appropriate and that experts are working to determine why the vaccine was less effective than expected.

“[S]cientists at FDA are collaborating with colleagues at Centers for Medicare & Medicaid Services to use a large database that includes details of the flu vaccines administered to four million individuals along with whether they were hospitalized for influenza or treated with antiviral medications for influenzalike illness,” Gottlieb explained.

“This work, which is still underway, will try to better understand why overall effectiveness with both the cell-based and egg-based vaccines was less than optimal. We’re also looking at the difference in effectiveness in people 65 years and older who were vaccinated with high-dose influenza vaccine and adjuvanted influenza vaccine to see if effectiveness was better than in those vaccinated with standard-dose vaccines.”

Vaccine Strains

For the trivalent vaccine, the committee voted unanimously (12 yes, 0 no) to include an A/Michigan/45/2015 (H1N1)pdm09-like virus. The panel voted unanimously to include an A/Singapore/INFIMH-16-0019/2016 (H3N2)-like virus, which is a change from the 2017-2018 vaccine.

The group voted by a large margin (11 yes, 1 abstain) to include a B/Colorado/06/2017-like virus (B/Victoria/2/87 lineage), which is a change from this season’s vaccine.

The committee also voted unanimously to include a B/Phuket/3073/2013-like virus (B/Yamagata/16/88 lineage) as the second influenza B strain in the quadrivalent vaccine.

Vaccine Effectiveness Lower Than Expected

Interim results for this season show that vaccination lowered the number of cases of medically attended influenza illness by 36%. Vaccine effectiveness against influenza A(H3N2) was 25% for all ages and 51% for children aged 6 months to 8 years. There were no statistically significant estimates of vaccine effectiveness against influenza A(H3N2) for other age groups. The vaccine was 67% effective against A(H1N1)pdm09 and 42% effective against influenza B (mostly B/Yamagata, not in inactivated influenza vaccine, trivalent).

“In terms of last year’s vaccine…even though we’ve had a bad flu year, the strains that were selected…were really good selections. They were as good as one could guess and make at the time. I don’t think we could’ve done any better, and I’m encouraged by the fact that particularly [in children aged 6 months] to 8 years old it’s almost 60% effective,” said temporary voting member Jack Bennink, PhD, senior managing epidemiologist, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.

Influenzalike Illness Activity Remains High Across the United States

Influenza A(H3N2) viruses were predominant during the 2017-2018 season; however, influenza B activity is rising. Influenzalike illness (ILI) activity fell from 7.4% during week 6 of 2018 to 6.4% during week 7. ILI activity continues to be higher than peak activity seen during many past seasons and is the highest observed since 2009. Hospitalization rates and mortality for adults could be as high or higher than those seen during the 2014-2015 season.

Most of the circulating influenza strains are like those in the 2017-2018 vaccine. The majority of influenza B infections were caused by B/Yamagata lineage viruses. The B/Victoria lineage viruses are the only ones showing clear antigenic drift but represent less than 1% of circulating viruses.

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Vedolizumab Relieves Refractory Crohn's Disease

Vedolizumab Relieves Refractory Crohn's Disease

VIENNA — Vedolizumab can lead to endoscopic remission in some patients with moderately to severely active Crohn’s disease that hasn’t responded to previous therapy, according to the VERSIFY study (NCT02425111), which builds on the findings of the GEMINI 2 and 3 trials.

This study “confirms that vedolizumab is a first-line biologic option after conventional therapy,” said investigator Silvio Danese, MD, PhD, from Humanitas University in Milan.

In fact, after treatment with the monoclonal antibody, 12% of participants achieved endoscopic remission: 20% of participants not previously treated with a TNF inhibitor and 6% of participants previously treated with a TNF inhibitor.

Endoscopic remission, the primary study outcome, “is an important treatment target that can influence the course of the disease,” Danese said here at the European Crohn’s and Colitis Organisation 2018 Congress, where he presented 26-week results.

“These results, although numerically not impressive, at least in TNF-exposed patients, are very encouraging because the population of this study consisted of patients with refractory Crohn’s disease,” said Gerassimos Mantzaris, MD, PhD, from Evangelismos, Ophthalmiatreion Athinon, and Polyclinic Hospitals in Athens, who was not involved in the study.

“And, in contrast to anti-TNF agents, vedolizumab is a slow-acting drug,” he told Medscape Medical News.

In another presentation at the congress, Renáta Bor, MD, from the University of Szeged in Hungary, and her colleagues reported that vedolizumab is associated with mucosal healing. However, their study was different from VERSIFY in several ways: treatment duration was shorter; both Crohn’s disease and ulcerative colitis were assessed; and people who had previously failed TNF inhibitor therapy were included in the study population.

VERSIFY Study

The 101 participants in the phase 3b, single-arm, multicenter VERSIFY study received an open-label standard induction dose of intravenous vedolizumab 300 mg on day 1 and at weeks 2, 6, 14, 22, up to week 26, and underwent screening colonoscopy at weeks 14 and 26. A central reader performed the endoscopic evaluations.

At baseline, mean Simple Endoscopic Score for Crohn’s Disease (SES-CD) score was 16 — remission was defined as a score of 4 or below — and mean Crohn’s Disease Activity Index (CDAI) score was 324. Of the participants, 55% had failed previous treatment with a TNF inhibitor, 40% had very high levels of C-reactive protein — above 10 mg/L — and all had one or more mucosal ulcerations on ileocolonoscopy.

At week 26, complete mucosal healing, defined as an absence of ulceration, was achieved by 15% of the overall study population: 24% of participants not previously treated with a TNF inhibitor and 7% of participants who failed previous TNF inhibitor therapy.

“I am impressed with the results of the complete mucosal healing, as more patients achieved this secondary end point: 15% overall, which is marginally inferior to the other secondary end point — the drop in SES-CD score by at least 50%,” Mantzaris pointed out.

Clinical Remission

At week 10, clinical remission, defined as a CDAI score of 150 or below, was achieved by 36% of all patients; this rose to 42% at week 26. Again, those not previously treated with a TNF inhibitor fared better than those previously treated, with 52% of those not previously treated achieving clinical remission at week 26.

Table. Endoscopic Outcomes at Week 26

Outcome	Overall, % (n = 101)	No Previous TNF Inhibitor, % (n = 46)	Previous TNF Inhibitor Failure, % (n = 55)
Remission	12	20	6
Response	25	28	22
Complete healing	15	24	7

 

Complete mucosal healing varied by segment of the GI system. “The large bowel had a tendency to heal more than the ileum,” Danese reported.

In terms of safety and tolerability, there were no new safety signals. Sixty-six participants experienced an adverse event and 11 experienced a treatment-associated adverse event, including two exacerbations of Crohn’s disease. There were no cases of liver injury or death.

“I believe that the rate of endoscopic response, remission, and complete healing will be higher in patients who maintain clinical remission on vedolizumab at the end of 1 year,” Mantzaris said.

“We are awaiting the 52-week data,” Danese added. “I think they will be available soon.”

Prospective, real-life studies are needed to confirm the usefulness of vedolizumab in Crohn’s disease, as well as whether cotreatment with an immunomodulator can increase the efficacy of vedolizumab, Mantzaris said.

The VERSIFY study was supported by Takeda Pharmaceuticals International. Danese is a member of the Takeda advisory board. Mantzaris has disclosed no relevant financial relationships.

European Crohn’s and Colitis Organisation (ECCO) 2018 Congress: Abstract OP023. Presented February 16, 2018.

Follow Medscape Gastro on Twitter @MedscapeGastro and Damian McNamara @MedReporter

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