Erenumab Not Effective for Chronic Cluster Headache
Preventive treatment with the calcitonin gene-related peptide (CGRP) receptor monoclonal antibody erenumab for 6 weeks was not associated with significant reductions in weekly headache attacks, pain severity, or attack duration in adults with chronic cluster headache (CCH), a new phase 2 placebo-controlled trial showed.
METHODOLOGY:
The CHERUB01 phase 2 12-week, double-blind, placebo-controlled randomized clinical trial was conducted at 11 sites in Germany between 2021 and 2023.
About 81 adults with CCH (mean age, 49 years; 74% men) who failed to respond to standard prophylactic therapies were randomly assigned to receive either subcutaneous erenumab (280 mg at baseline, followed by 140 mg at week 4) or a matching placebo.
The primary endpoint was change in the mean number of weekly CH attacks from baseline to weeks 5 and 6.
Secondary endpoints included the proportion of patients achieving a ≥ 50% reduction in attacks and the number of participants with Patient Global Impression of Improvement (PGI-I) scores of 1 or 2 at week 6. Exploratory endpoints included reduction in CH attack duration and change in mean pain severity on the numeric pain rating scale.
TAKEAWAY:
The primary endpoint was not met. Although there was a greater reduction in the mean number of weekly attacks for the erenumab group compared to the placebo group, the difference was not statistically significant (-7.3 vs -5.9 attacks per week; 95% credible interval, -5.7 to 2.8).
There was no significant difference between groups in the proportion of participants achieving a ≥ 50% reduction in weekly attacks, the number of patients with improved PGI-I scores, changes in attack duration, or change in pain severity.
Adverse events were more common in the erenumab group compared to the placebo group (66% vs 43%), with most considered to be mild or moderate.
IN PRACTICE:
'Erenumab failed to show a benefit over placebo in patients with CCH, indicating that blockade of peripheral CGRP receptors has no beneficial role in the prophylaxis of CCH,' the investigators wrote.
'To date, all double-blind controlled trials in CCH using an mAb affecting the CGRP pathway were negative, leading to the conclusion that future research should revisit the role of CGRP in CCH,' they added.
SOURCE:
This study was led by Jasper Mecklenburg, MD, Charité – UniversitätsmedizinBerlin, Berlin, Germany. It was published online on June 17 in JAMA Network Open.
LIMITATIONS:
Data on patients who progressed from episodic headache to CCH were missing. Additionally, the onset timing of current CCH episodes was unclear, with no detailed records of past steroid responses or reasons for prior treatment failures with verapamil or lithium, which relied on patient recall.
DISCLOSURES:
This trial was funded by a grant from Novartis Pharma GmbH to Charité – UniversitätsmedizininBerlin. Several investigators reported having financial ties with various sources including the funding company. Full details are listed in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
Hashtags
Try Our AI Features
Explore what Daily8 AI can do for you:
Comments
No comments yet...
Related Articles
Associated Press
30 minutes ago
- Associated Press
cooldown°earth welcomes North Rhine-Westphalia (NRW) funding for matterr / – Public funds and public welfare capital accelerate circular technology -
The non-profit cooldown°earth foundation congratulates its portfolio company matterr on receiving funding confirmation from the state of North Rhine-Westphalia as part of the EFRE/JTF program ' of Economic Affairs and Climate Protection Mona Neubaur presented the funding approval on August 6 in Düsseldorf. To help end the export of waste from industrialised nations—a practice that currently places a disproportionate burden on the world's poorest countries—matterr has developed a globally patented solution capable of repeatedly transforming waste back into high-quality raw materials. With this funding, matterr can accelerate the construction of its second plant, now on a small industrial scale, in North Rhine-Westphalia. The core technology is the depolymerization of PET under mild conditions. This allows mixed waste such as multi-layer packaging or mixed textile fabrics to be broken down into their primary components and fossil raw materials to be replaced on a large scale. By returning the monomer-based process to primary material quality, it enables molecular upcycling: Polyester textiles, which previously could only be recycled for low-quality applications, are now being used to create products of the highest quality – not only new textiles, but even packaging that is approved for food contact. 'This is a unique partnership,'says Wolfgang K. Hoever,founder of cooldown°earth. 'A charitable foundation takes the lead, the state follows – and the result is infrastructure that turns hard-to-recycle waste into a circular GreenTech product. This is great news for climate protection and for our region as a business location.' The funding commitment awarded to matterr is not only the first from this programme but also themaximum possible grant amount of €30 million. The planned NRW facility is scheduled to start operations in 2027 with an annual capacity of 10,000 tonnes. cooldown°earth is not the recipient of the funding, but an early investor and enabler. Any potential returns from its stake will, in accordance with its statutes, be reinvested in non-profit climate and environmental protection projects. Background About cooldown°earth: Thecooldown°earth foundationis a private, non-profit foundation based in Krefeld, Germany. Founded in 2013 by Dr. Annekathrin Edelmann and Wolfgang K. Hoever, it works to promote social cohesion and climate protection. Projects include the Digital Climate School, which helps schools integrate education for sustainable development into their curricula. The foundation fosters skills in using new technologies for sustainability and strengthens motivation for the responsible use of the planet's natural
Health Line
38 minutes ago
- Health Line
Do GLP-1 Weight-Loss Drugs Cause Vision Loss? What to Know
Studies have linked GLP-1 medications to various eye conditions, some of which may lead to vision loss. Despite these findings, a clear link has yet to be established, and much of the evidence remains inconsistent. People should be aware of potential eye disease and blindness risks when discussing a GLP-1 with their doctor. The debate over whether GLP-1 medications raise the risk of eye conditions that could lead to vision loss continues. Scientists have been closely studying this association as more people turn to these widely prescribed drugs for weight management. Some studies have suggested a link, but the overall evidence has been inconsistent. However, when a potential side effect becomes as serious as vision loss or blindness, even a remote possibility is worth investigating. GLP-1 drugs are a class of medications used to treat obesity and type 2 diabetes that include semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro, Zepbound). They work by mimicking naturally occurring hormones that help regulate blood sugar, promote satiety, and reduce appetite. While GLP-1s are generally well tolerated and offer numerous health benefits — from weight loss and better glucose control to a lower risk of cardiovascular disease — research suggests they could increase the risk of certain serious eye conditions. Previous research has linked GLP-1 drugs to a sudden, vision-threatening condition called nonarteritic anterior ischemic optic neuropathy (NAION) and to 'wet' age-related macular degeneration. The risk of developing these conditions is relatively low. However, they are serious and should be factored into the risk–benefit discussion when considering GLP-1 therapy with a doctor. As a flurry of new research offers a clearer picture of how GLP-1 drugs may affect eye health, Healthline spoke with experts to help break down the findings. GLP-1 drugs and eye disease Three new studies investigated the link between GLP-1s and eye disease, but each employed distinct methods and arrived at different conclusions. A new study compared the effects of semaglutide or tirzepatide with other antidiabetic medications — such as insulin and metformin — on optic nerve conditions, including NAION, in patients with type 2 diabetes. The retrospective cohort study, published on August 11 in JAMA Network Open, included nearly 160,000 patients, evenly split into two groups: one taking GLP-1s and one taking other antidiabetic medications. Over two years of follow-up, those taking a GLP-1 had higher rates of NAION and other optic nerve conditions than those in the comparison group. There were 93 patients with other optic nerve disorders in the semaglutide or tirzepatide group, and 54 patients with these disorders in the comparison group. The study did not specify the types of other optic nerve disorders. 'Newer GLP-1RAs have lots of benefits. This study provides evidence of their potential risks. For each patient, the risk-benefit tradeoff critically depends on a patient's clinical characteristics and their preferences and clinicians' recommendations,' senior study author Rong Xu, PhD, professor and director of the Center for AI in Drug Discovery at Case Western Reserve University, told Healthline. A separate retrospective study, also published in August in the same journal, reached a different conclusion. In a large cohort of patients with type 2 diabetes, researchers found that GLP-1 use was not associated with a higher incidence of NAION but was linked to another eye condition: diabetic retinopathy. During a two-year follow-up, 5,037 patients taking a GLP-1 developed diabetic retinopathy, compared with 4,938 who were not — a 7% increased risk. In a twist, the study found that although there was a small increase in diabetic retinopathy, GLP-1 use appeared to protect against the condition's progression and sight-threatening complications. A subgroup of patients in the study had pre-existing diabetic retinopathy. Those who took a GLP-1 had a lower risk of complications, including progression to proliferative diabetic retinopathy, diabetic macular edema, vitreous hemorrhage, and neovascular glaucoma. They were also less likely to require medical, surgical, or laser treatments for their eyes. Most notably, GLP-1 use was associated with a significantly lower incidence of blindness from any cause. Another study — a meta-analysis and review of 78 trials involving more than 73,000 participants — concluded that semaglutide was associated with an increased incidence of NAION but emphasized that evidence for a causal link remains inconclusive. The review, published on August 14 in JAMA Ophthalmology, found that semaglutide neither increased nor reduced the risk of eye disorders, including diabetic retinopathy. It's important to note that all three studies can only identify correlations and cannot establish that taking a GLP-1 causes these eye disorders. Studies so far have also focused almost exclusively on patients with type 2 diabetes, so it's unclear what effect GLP-1s have on eye conditions in individuals taking them for weight loss. Making sense of GLP-1s and eye health If you're having trouble making sense of what these conflicting findings mean — especially if you already take a GLP-1 or are considering one — you're not alone. Here's a quick summary on GLP-1s and various eye conditions, and what experts have to say about them: NAION NAION causes sudden blindness in one eye, usually after waking, that is caused by a lack of blood flow to the optic nerve. The condition is elusive, and not well understood. The condition is serious, but despite an apparent increased incidence among patients taking GLP-1s, the condition is still uncommon. 'NAION is rare in general,' said Xu. 'For patients with high risk of developing NAION (e.g., those with diabetes, hypertension) who are taking GLP-1RAs, ophthalmologists may increase vigilance,' she said. Linda Lam, MD, MBA, an ophthalmologist with Keck Medicine of USC, who wasn't involved in the research, tells Healthline that it's too early to make a 'definitive connection' between NAION and GLP-1s. 'To make a correlation that GLP-1s cause NAION would be a big leap,' she said. Diabetic retinopathy Diabetic retinopathy is a complication of type 1 and type 2 diabetes that may lead to vision loss. It is the most common cause of preventable blindness in the United States. Though it may seem counterintuitive, antidiabetic medications that improve blood glucose may worsen this condition. 'It's better to be cautious and protective with vision. So, if a patient has started on a GLP-1 and they already have some diabetic retinopathy, I would just have them come in sooner to see their eye care provider,' said Lam. 'Wet' age-related macular degeneration A recent study published in June found that patients with type 2 diabetes who took GLP-1s were more than twice as likely to develop wet AMD as those who did not. Researchers also identified a dose response, meaning that the longer the patients took a GLP-1, the more likely they were to develop the condition. However, there still needs to be more research to substantiate this link. 'We need to have a lot more studies before we can make these cause and effect determinations. But, anyone who has neovascular AMD and is on a GLP-1 needs to be monitored more closely,' said Lam. The bottom line: GLP-1s have many health benefits, and while there is some evidence to support an association between them and serious eye conditions, that link should not be overstated, and must be considered within the greater context of your individual health. Patients with diabetes should get regular eye exams, regardless of whether they are taking a GLP-1, but taking the medication may be one more reason to schedule an exam. 'GLP-1s have potentially good long-term effects for long-term health in patients with diabetes or obesity. But doctors should be much more cautious and aware of visual complications while they're on these medications, especially when their glycemic numbers go down rapidly. The threshold for when to see your eye care provider or retina specialist should be lower,' Lam said.
Medscape
an hour ago
- Medscape
Management of Hypertension in Primary Care
Hypertension is the most common chronic condition that primary care physicians treat. Knowledge about the causes and effective treatment strategies have evolved over the decades since I attended medical school, and I want to highlight some of the most useful approaches I have found over the years. What are the most common causes of secondary hypertension? Most hypertension (90%-95%) is essential hypertension. In medical school, I learned a list of rare diseases to consider as causes of secondary hypertension like pheochromocytoma, coarctation of the aorta, and Cushing syndrome. In the real world, the diagnoses with highest prevalence of secondary hypertension are obstructive sleep apnea (25%-50%), hyperaldosteronism (8%), atherosclerotic renal artery stenosis (5%), and drug or alcohol abuse (4%). The rare diseases listed above account for 0.1% or less of secondary hypertension. What is the best initial treatment for patients just diagnosed with hypertension? The biggest change from what I was taught in medical school is that for most patients, we should start with two-drug therapy to achieve the blood pressure (BP) goal if the initial BP is more than 20/10 mm Hg above the target BP goal. Patients with stage 1 hypertension are usually started on one medication if the goal is more modest BP lowering. What if your initial treatment with a single drug does not achieve its goal? Douglas S. Paauw, MD The standard approach for many years was to increase the dose of the single BP medication with the hope that there would be a more pronounced BP response. J.R. Benz and colleagues looked at the BP effect of doubling the dose of valsartan from 80 mg to 160 mg. The difference was an additional BP lowering of only 3 mm Hg/0.8 mm Hg. Patients who received a second drug (hydrochlorothiazide) in addition to 80 mg of valsartan rather than doubling the valsartan dose had an average reduction in BP of 12 mm Hg/6 mm Hg. In a meta-analysis comparing monotherapy with combination therapy for lowering BP, adding another drug lowered BP five times more than doubling the dose of the initial antihypertensive drug. What is the best approach to treating resistant hypertension? According to my training, patients with resistant hypertension needed a workup for secondary hypertension and rarely used drugs like clonidine and minoxidil were in play. De Jager and colleagues evaluated renal denervation in hypertension treatment. As part of the study, stored blood samples collected at study entry were evaluated for adherence to prescribed antihypertensive medications. In 80% of patients, fewer drugs were detected than prescribed. This high rate of nonadherence emphasizes that the first place to start in treatment of resistant hypertension is to carefully assess adherence. For patients with true resistant hypertension, de Souza et al studied 175 patients taking at least three antihypertensive medications and documented adherence. All patients were then given spironolactone, with a mean decrease in systolic BP of 16 mm Hg and diastolic BP of 9 mm Hg. Adding a mineralocorticoid receptor antagonist is recommended in the American College of Cardiology/American Heart Association guidelines. Recent data collected by Lee and colleagues show that amiloride is equivalent to spironolactone in patients with resistant hypertension, with systolic BP reductions of 13.6 mm Hg. Pearls:
