People with cluster headaches may be more than three times more likely to have other medical conditions such as heart disease, mental disorders and other neurologic diseases, according to a study published in Neurology.
Cluster headaches are short but extremely painful headaches that can occur many days, or even weeks, in a row. The headaches can last anywhere from 15 minutes to three hours.
“Around the world, headaches have an incredibly negative impact on people’s quality of life, both economically and socially,” said study author Caroline Ran, PhD, of the Karolinska Institutet in Stockholm, Sweden. “Our results show that people with cluster headaches not only have an increased risk of other illnesses, those with at least one additional illness missed four times as many days of work due to sickness and disability than those with just cluster headaches. They also have a higher chance of a long-term absence from work.”
The study involved 3240 people with cluster headaches ages 16–64 in Sweden who were compared to 16 200 matched controls. The majority were men, typical of cluster headache.
Researchers looked at work records and disability benefits to determine how many days during a year people were absent from work due to sickness and disability.
Among those with cluster headaches, 92%, or 2977 people, had at least one additional illness. Of those without cluster headaches, 78%, or 12 575 people, had two or more illnesses.
Of those with cluster headaches, more women had additional illnesses than men, 96% and 90% respectively.
The average number of days a person was absent due to sickness and disability was nearly twice as high among people with cluster headaches with 63 days compared to those without cluster headaches with 34 days.
People with cluster headaches and at least one additional illness had four times as many absence days compared to people with cluster headaches who did not have an additional illness.
“Increasing our understanding of the other conditions that affect people with cluster headache and how they impact their ability to work is very important,” added Ran. “This information can help us as we make decisions on treatments, prevention and prognoses.”
A limitation of the study was that information on personal data, such as smoking, alcohol consumption and BMI, which could affect the occurrence of diseases, was not available.
FexD, a new version of fexaramine developed by Salk Institute researchers, acts like a master reset switch in the intestines and has previously been found to lower cholesterol, burn fat, and ward off colorectal cancer in mice. Now, the team reports in Proceedings of the National Academy of Sciences that FexD can also prevent and reverse intestinal inflammation in mouse models of inflammatory bowel disease.
“The Salk-developed drug FexD provides a new way to restore balance to the digestive system and treat inflammatory diseases that are currently very difficult to manage,” says senior author and Salk Professor Ronald Evans, director of Salk’s Gene Expression Laboratory and March of Dimes Chair in Molecular and Developmental Biology.
Inflammatory bowel disease (IBD), which includes both Crohn’s disease and ulcerative colitis, is characterised by an excess of immune cells and inflammatory signalling molecules known as cytokines in the gut. Existing treatments, which mostly work by either suppressing the entire immune system or by targeting individual cytokines, are only effective for some patients and carry a host of side effects.
For more than two decades, Evans’s lab has studied Farnesoid X receptor (FXR), a master regulator protein that senses the bile acids delivered to the digestive system to help digest food and absorb nutrients. When FXR detects a shift in bile acids at the beginning of a meal, it prepares the body for an influx of food by flipping on and off dozens of cellular programs related to digestion, blood sugar, and fat metabolism.
In 2015, Evans and his colleagues developed a pill called fexaramine that activates FXR in the gut. The pill, they initially showed, can stop weight gain and control blood sugar in mice. In 2019, they showed that FexD – an updated version of fexaramine – also prevented cancer-associated changes to stem cells in the gut. Their work suggested that FXR also played a role in regulating inflammation.
“Every time you eat, you’re causing small amounts of inflammation in your gut as your intestinal cells encounter new molecules. FXR makes sure inflammation stays under control during normal feeding,” says Senior Staff Scientist Michael Downes, co-corresponding author of the new paper.
In the new work, Evans’ group discovered that activating FXR can be used to ease symptoms in inflammation-driven diseases. When the researchers gave mice with IBD a daily dose of oral FexD, either before or after the onset of intestinal inflammation, the drug prevented or treated the inflammation. By activating FXR, FexD reduced the infiltration of a class of highly inflammatory immune cells called innate lymphoid cells. In turn, levels of cytokines already implicated in IBD decreased to levels normally seen in healthy mice.
“When we activate FXR, we restore appropriate signalling pathways in the gut, bringing things back to a homeostatic level,” says Senior Research Scientist Annette Atkins, co-author of the study.
Since FXR acts more like a reset button than an off switch for the immune system, cytokines are not completely blocked by FexD. This means that the immune system continues functioning in a normal way after a dose of FexD. The compound still must be optimised for use in humans and tested in clinical trials, but the researchers say their findings provide important information about the complex links between gut health and inflammation and could eventually lead to an IBD therapeutic.
“In people with IBD, our strategy could potentially be very effective at preventing flare-ups and as a long-term maintenance drug,” says first author Ting Fu, previously a postdoctoral fellow at Salk and now an assistant professor at the University of Wisconsin-Madison.
Multiple Sclerosis (MS) is almost always accompanied by fatigue, a massive tiredness that is described by the vast majority of patients as the most distressing symptom. Researchers have now identified light therapy as a promising nonpharmaceutical treatment option: patients included in the study showed a measurable improvement after just 14 days of use. Their study’s results were published in the Multiple Sclerosis Journal – Experimental, Translational and Clinical.
The research team led by Stefan Seidel from the Department of Neurology at MedUni Vienna and AKH Vienna, relied not only on surveys but also on objective measurements when selecting the test persons – the first study of its kind to do so. For example, sleep-wake disorders were ruled out in the 26 participating MS patients, particularly with the assistance of various sleep medicine examinations. “In this manner, for example, we ensured that MS patients with fatigue do not suffer from sleep apnoea or periodic leg movements during sleep. Both are sleep disorders that can lead to fatigue in everyday life,” elaborated study leader Stefan Seidel.
Performance improvement
The test persons – all patients of the Neurology Department at MedUni Vienna and AKH Vienna – were equipped with commercially available light sources for self-testing at home: Half of the participants received a daylight lamp with a brightness of 10 000 lux (equivalent not to a cloudy day but not direct sunlight), while the other half received an identical lamp that emitted a red light with an intensity of <300 lux due to a filter (about the intensity of an office working environment). While the red light used by the control group showed no effect, the researchers were able to observe measurable successes in the other group after only 14 days: The participants who used their 10 000 lux daylight lamp for half an hour every day showed improved physical and mental performance after only a short period of time. In addition, the group of participants who had consumed bright light displayed less daytime sleepiness in comparison with the other group.
A nonpharmaceutical approach
Fatigue is a severe form of tiredness and fatigability that occurs in 75 to 99 percent of people with MS and is described as particularly distressing. Nerve damage triggered by MS is one possible cause. In addition to behavioural measures, such as regular rest breaks, various medications are currently available to alleviate fatigue, but some of these are associated with severe side effects. “The findings from our study represent a promising non-drug therapeutic approach,” Stefan Seidel said. However, the results still need to be confirmed in a subsequent larger-scale study. The reinvigorating mechanism of light therapy on MS patients will also be the subject of further scientific research.
New research published in the Annals of Clinical and Translational Neurology has identified three genes and their expressed proteins that may be involved in the pathogenesis of multiple sclerosis.
By comparing information on the genes and proteins expressed in the brains of thousands of individuals with and without multiple sclerosis, investigators discovered different expression levels of the SHMT1, FAM120B, and ICA1L genes (and their proteins) in brain tissues of patients versus controls.
Protein abundance alteration in human brain has linked to MS. For instance, protein abundance of glial fibrillary acidic protein (GFAP), myelin basic protein (MBP)3 and thymosin β-46 was dysregulated in lesions from MS patients’ brain, and these proteins have been used for disease severity prediction and targeted therapy lately. In addition, compared to bodily fluid samples like cerebrospinal fluid and plasma, human brain tissue directly reflects the pathophysiology changes of MS and has become increasingly important in disease biomarker identification. However, few studies focused on specific subregions of the brain, ignoring the possible differences in protein types and abundance between subregions with distinct functions.
Studying the functions of these genes may uncover new information on the mechanisms involved in the development and progression of multiple sclerosis. “Our findings shed new light on the pathogenesis of MS and prioritised promising targets for future therapy research,” the authors wrote.
An international clinical trial of a new monoclonal antibody therapy showed promising results for patients moderate to severe atopic dermatitis both while taking the drug and up to 20 weeks after the therapy was stopped, according to Mount Sinai researchers in The Lancet.
The researchers said the results indicate that the new biologic, rocatinlimab, has the potential to change the genetic makeup of a person’s atopic dermatitis for the long term, and possibly help sustain lasting results without continued use. Rocatinlimab inhibits OX40. an immune molecule involved in activating inflammatory cells that play a key role in the development of atopic dermatitis and other inflammatory diseases.
“Atopic dermatitis, the most common type of eczema, is a debilitating chronic inflammatory skin disease that affects 1 in 10 Americans and millions of people worldwide,” said Emma Guttman, MD, PhD, Mount Sinai professor. “It often develops at a very young age, causing the skin to become inflamed, red, extremely itchy, painful, and very dry – all symptoms that greatly affect a patient’s quality of life. We are very optimistic about the results of this trial and the potential for disease modification and long-lasting effects to improve patients’ quality of life.”
In this phase 2b multicentre, double-blind, placebo-controlled study, 274 patients were recruited and (rocatinlimab: n = 217; placebo: n = 57) equally randomised to rocatinlimab every four weeks (150mg or 600mg) or every two weeks (300mg or 600mg) or subcutaneous placebo up to week 18, with an 18-week active-treatment extension and 20-week follow-up.
Percent change from baseline in the Eczema Area and Severity Index (EASI) score was assessed as the primary endpoint at week 16, and significance versus placebo was achieved with all active rocatinlimab doses (-48% to -61%) doses compared to placebo (-15%). All active dose cohorts also continued improving after week 16, and most patients maintained the response for at least 20 weeks off treatment.
The results support rocatinlimab as a safe and effective treatment for moderate to severe atopic dermatitis, with potentially long-lasting efficacy and disease modification. Adverse events reported were generally similar between rocatinlimab groups. Common adverse events during the double-blind period included fever, chills, headache, aphthous ulcers (canker sores), and nausea.
“At week 36, all participants had been on the treatment for at least 18 weeks,” added Dr Guttman, senior author of the study. “By this time, we saw that while the drug achieved the primary endpoints in all doses versus the placebo, it’s also a drug that improves over time, which is really unusual and unique among currently available treatment options.”
Researchers plan to continue this investigation in a phase 3 program in 2023. Future studies will also include a larger study population, longer follow-up, and explore combination therapy (eg with topical corticosteroids).
Canadian singer Celine Dion has revealed that she has been diagnosed with a very rare neurological disease called Stiff Person Syndrome (SPS), BBC News reports. The disease causes muscle spasms, interfering with daily activities. Injuries can be sustained from falls caused by spasms experienced while walking.
The 54-year-old singer had been battling with muscle spasms, and since the disease interferes with her singing, she has cancelled all of her concerts scheduled for 2023, putting them off to 2024.
SPS is an extremely rare disease, thought to affect only one in a million individuals. As such, relatively little is known about it and what causes it, although it is associated with autoimmune disorders and often misdiagnosed as Parkinson’s disease.
After a hiatus from 2014 to be with her husband while he battled cancer, she returned to the stage in 2019 with her new album Courage. This tour had a number of cancellations due to the COVID pandemic.
Speaking on an Instagram post, Dion said that she had “a great team of doctors working alongside me to help me get better” and had the support of her “precious children”.
The singer explained: “I’m working hard with my sports medicine therapist every day to build back my strength and my ability to perform again, but I have to admit it’s been a struggle.
“All I know is singing. It’s what I’ve done all my life and it’s what I love to do the most.
“I miss you so much. I miss seeing all of you [and] being on the stage, performing for you.
“I always give 100 per cent when I do my show but my condition is not allowing me to give you that right now.”
What is stiff person syndrome?
According to the National Institute for Neurological Disorders, SPS is characterised by “fluctuating muscle rigidity in the trunk and limbs and a heightened sensitivity to stimuli such as noise, touch, and emotional distress, which can set off muscle spasms. Abnormal postures, often hunched over and stiffened, are characteristic of the disorder. People with SPS can be too disabled to walk or move, or they are afraid to leave the house because street noises, such as the sound of a horn, can trigger spasms and falls. SPS affects twice as many women as men.”
A definitive diagnosis can be made by measuring the level of glutamic acid decarboxylase (GAD) antibodies in the blood, which is elevated in people with SPS. GAD is the rate-limiting enzyme that catalyses the conversion of glutamate to GABA
As for management, the symptoms can be well controlled. Pharmacological treatment includes IVIg, anti-anxiety drugs, muscle relaxants, anti-convulsants, and pain relievers.
Work continues for better treatments; so far rituximab proved ineffective. At present, research is focused on aetiology and the role of anti-GAD antibodies.
To date, there has been little research into identifying the bacteria found in severe oral infections, despite long-suspected links to other diseases. Now, a study from Karolinska Institutet has characterised the microbial composition of these, with many known to be linked to other disease. The study is published in Microbiology Spectrum.
There is growing evidence linking oral health and common diseases, such as cancer, cardiovascular disease, diabetes and Alzheimer’s disease. However, there have been few longitudinal studies identifying which bacteria occur in infected oral- and maxillofacial regions.
Researchers at Karolinska Institutet have now analysed samples collected between 2010 and 2020 at the Karolinska University Hospital in Sweden from patients with severe oral infections and produced a list of the most common bacteria.
“We’re reporting here, for the first time, the microbial composition of bacterial infections from samples collected over a ten-year period in Stockholm County,” says Professor Margaret Sällberg Chen of the Department of Dental Medicine. “The results show that several bacterial infections with link to systemic diseases are constantly present and some have even increased over the past decade in Stockholm.”
A role in other diseases
The study shows that the most common bacterial phyla amongst the samples were Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria, while the most common genera were Streptococcus spp, Prevotella spp, and Staphylococcus spp.
“Our results provide new insight into the diversity and prevalence of harmful microbes in oral infections,” says Professor Sällberg Chen. “The finding isn’t only of importance to dental medicine, it also helps us understand the role of dental infection in patients with underlying diseases. If a certain bacterium infects and causes damage in the mouth, it’s very likely that it can be harmful to tissues elsewhere in the body as the infection spreads.”
The research group has previously shown that the occurrence of oral bacteria in the pancreas reflects the severity of pancreatic tumours.
Improve diagnostics and therapy
The study was conducted using 1014 samples from as many patients, of whom 469 were women and 545 men, and a mass-spectrometric method called MALDI-TOF that rapidly identifies individual living bacteria in a sample, but that is rarely used in dental care.
“Our study was a single centre epidemiology study and to ensure the validity of the results we need to make more and larger studies,” says adjunct Professor Volkan Özenci at the Department of Laboratory Medicine. “We now hope that dentists will collaborate with clinical microbiology laboratories more to gain a better understanding of the bacteria that cause dental infections, to improve diagnostics and therapeutic management of oral infections.”
The study is part of Khaled Al-Manei’s doctoral thesis, the next step of which is a similar epidemiological study of fungal infections in the mouth that aims to identify new fungi and microbes and understand what causes their possible malignancy.
By measuring the proportions of certain immune cells in the cerebrospinal fluid when diagnosing amyotrophic lateral sclerosis (ALS), it is possible to predict the disease’s speed of progression, according to a study from Karolinska Institutet published in Nature Communications.
ALS is a rare, but fatal disease that affects the nerve cells and leads to paralysis of voluntary muscles and death. This new research offers a way to predict the course of the disease in ALS patients.
Between March 2016 and March 2020, researchers collected fresh blood and cerebrospinal fluid from 89 patients in Stockholm who had recently been diagnosed with ALS, and followed-up until October 2020.
The study shows that a high proportion of so-called effector T cells are associated with a low survival rate. At the same time, a high proportion of activated regulatory T cells indicate a protective role against the rapid disease progression. The findings provide new evidence for the involvement of T cells in the course of the disease and show that certain types of effector T cells accumulate in the cerebrospinal fluid of ALS patients.
“The study could contribute to the development of new treatments that target immune cells to slow down the course of the disease,” says study first author Solmaz Yazdani, a doctoral student at the Institute of Environmental Medicine at Karolinska Institutet.
The next step in her research is to study how T cells contribute to the course of the disease.
“We have plans to collect samples from these individuals to study changes in the immune cells over time. In addition, we want to study effector T cells in more detail to understand their role in ALS.”
A recent phase 2 clinical trial published in Arthritis & Rheumatologyhas reported promising results for deucravacitinib, an oral inhibitor tyrosine kinase 2 (TYK2) inhibitor, in patients with active lupus.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterised by the presence of antinuclear autoantibodies and diverse clinical manifestations. Treatment often lacks efficacy for SLE patients, and current therapies are associated with undesirable side effects.
TYK2 is an intracellular kinase that mediates signalling of key cytokines involved in the pathogenesis of SLE. A biologic agent targeting the type I interferon (IFN) receptor has been approved in SLE. Deucravacitinib is an oral, selective, allosteric inhibitor of TYK2 that binds the regulatory domain and locks the enzyme in an inactive state distinguishing it from JAK inhibitors that bind the highly conserved active domain
For the trial, adults with active SLE were enrolled from 162 sites in 17 countries. Patients (n = 363) were randomised 1:1:1:1 to receive deucravacitinib 3mg twice daily, 6mg twice daily, 12mg once daily, or placebo. The primary endpoint was SRI-4 and secondary outcomes were assessed on a variety of disease activity measures.
At week 32, the percentage of patients experiencing benefits was 34% with placebo compared with 58%, 50%, and 45% with the respective deucravacitinib regimens.
Rates of adverse events were similar across groups, except higher rates of infections and cutaneous events, including rash and acne, with deucravacitinib treatment. Rates of serious adverse events were comparable, with no deaths, opportunistic infections, tuberculosis infections, major adverse cardiovascular events, or thrombotic events reported.
Some cases of tuberculosis (TB) can be successfully treated in as little as two months – a third of the current standard of six months in South Africa and most other countries. This is according to early findings from the landmark TRUNCATE TB trial presented at last week’s Union World Conference on Lung Health.
Nick Paton, a professor of Infectious Diseases at the National University of Singapore and the chief investigator of the TRUNCATE trial, explains that the standard six-month treatment for drug-susceptible TB (DS-TB) is actually overtreating a lot of people who have the disease. The reason for the six-month mark for TB treatment is that a minority of TB patients need the long treatment regimen to avoid relapse, but the majority would be cured before the six-month mark.
Essentially, it’s a blunt, but generally, effective instrument used to protect a minority of TB patients.
The TRUNCATE trial set out to see if a two-month (eight weeks) novel combination of TB regimens would be feasible when compared to the standard six-month (24 weeks) treatment regimen. According to Paton, trial participants in the experimental arms of the study were initially given eight weeks of treatment, with the option of extending treatment to 10 to 12 weeks if they had persistent clinical disease after the eight-week treatment. If there was still active TB after that, participants were switched to the standard six-month treatment.
Study participants were monitored regularly through follow-up visits, which included TB symptom screening once a month and sputum smear tests every one to three months.
“The core [of the strategy] is it’s a very short period of initial treatment, plus you then do the monitoring and pick up people [who relapsed] early,” Paton says.
A total of 674 trial participants were recruited from March 2018 to March 2022 across 18 sites in Thailand, Indonesia, the Philippines, Uganda, and India. Four patients withdrew from the trial and 10 participants died during the trial.
Paton tells Spotlight that the overall death rate was low and there was no difference in the death rate between the standard treatment arm and the TRUNCATE strategy arms. The causes of death were mixed, he adds, and often the precise cause was unknown
For the final results, 660 participants were evaluated at week 96. In other words, about two years of follow-up occurred.
Encouraging results
Paton explains that the trial used the TRUNCATE strategy, which initially involved using four treatment arms containing a novel combination of TB drugs and comparing the results to a control arm consisting of the standard six-month treatment. Later, two TRUNCATE strategy arms were selected to complete the latter half of the study. He notes that it was a pragmatic decision to stop two of the arms, to ensure better data.
“You do substantially cut down the amount of time on treatment overall.”
Professor Nick Paton, chief investigator of the TRUNCATE trial.
In the first of the two remaining experimental arms, 184 study participants received a regimen consisting of high-dose rifampicin (35mg per kg, reduced to 20mg per kg as a precaution following a liver injury-related death), isoniazid, pyrazinamide, ethambutol, and linezolid (600mg). In the second, 189 study participants received a regimen consisting of bedaquiline (400mg/d for two weeks then 200mg three times a week), isoniazid, pyrazinamide, ethambutol, and linezolid (600mg). The standard treatment arm had 181 participants.
In the standard treatment arm, 98% completed treatment and 3% had to be re-treated before week 96.
In the TRUNCATE strategy arms, overall, 91% completed the eight-week treatment and stopped treatment by week 12. 17%, (ranging from 13 to 23% by arm) had re-treatment, and 2% of participants did not complete initial treatment due to withdrawing from the trial, death, or defaulting on treatment.
A comparison of the two experimental TRUNCATE arms with the standard treatment arm showed that the TRUNCATE arm with bedaquiline and linezolid was non-inferior to the standard treatment arm, while the high dose rifampicin and linezolid arm fell just short of meeting the non-inferiority criteria. Efficacy was calculated based on the proportion of unsatisfactory outcomes at week 96. Unsatisfactory outcomes were classified as death, still having active TB, or still being on TB treatment at week 96.
“The idea was that if we added those [unsatisfactory outcomes] up and that was the same in the standard treatment arm as the TRUNCATE strategy arm then that shows that this strategy in principle, can work,” Paton tells Spotlight.
The mean total days on treatment were reduced in the TRUNCATE strategy arms when compared to the standard treatment arm, which was 180 days. For high-dose rifampicin-linezolid, the average total days on treatment was 106 days, and in the bedaquiline-linezolid arm, it was 85 days.
“So, clearly the net effect is to decrease the average time on treatment,” Paton says. “You do substantially cut down the amount of time on treatment overall.”
He adds that the proportion of participants that had Grade 3 or 4 adverse events, serious adverse events, or who died did not differ between the standard treatment arm and the TRUNCATE strategy arm. The proportion of participants with respiratory disability at week 96 also did not differ.
The only cases of acquired drug resistance were two cases observed in the bedaquiline and linezolid arm. This is a frequency of 1.1% according to Paton. One of these participants missed several treatment doses, while the other did not miss any doses. Both were successfully re-treated.
Initially, they wanted to enroll participants who were co-infected with HIV in the later stages of the trial, but none could be enrolled in time, so currently there is no data on how well it works in people living with HIV who also have TB, says Paton.
“The trial has shown that alternatives to systematically over-treating the large majority of people with TB can be successful. This is an important new research direction which has the promise to improve outcomes for patients and programmes,” Paton says. “The strategy may be refined in future to improve outcomes using alternative drug regimens or alternative approaches to monitoring. Ongoing analysis from the trial will further enhance our understanding.”
PK and safety data
At last week’s conference, Christopher Cousins, project leader of the TRUNCATE trial presented the first level of pharmacokinetic (PK) analysis from the trial. The PK results were taken from week eight of the study.
AUC for the high-dose rifampicin was four to six times higher than in the standard dose and exceeded the proposed efficacy targets in the majority of patients.
After fasting overnight, participants took an observed dose of their medication at the trial site and had blood sampling done over a 12-hour period. The data is based on 96 participants in the two experimental arms.
He says the AUC (which represents total drug exposure over time – AUC = area under the curve) for the high-dose rifampicin was four to six times higher than in the standard dose and exceeded the proposed efficacy targets in the majority of patients. This supports the hypothesis that high-dose rifampicin would enhance treatment sterilisation in the eight-week regimen.
The data also showed what seems to be a drug-drug interaction between rifampicin and linezolid, but this didn’t appear to be significant enough to abolish anti-mycobacterial efficacy.
According to Cousins, the bedaquiline concentrations at the end of week eight in the bedaquiline and linezolid arm were comparable to the concentrations seen after 24 weeks of treatment for drug-resistant TB (currently both bedaquiline and linezolid are part of the standard treatment for DR-TB, but not for DS-TB).
When asked how well monitoring participants in the TRUNCATE arms after they stopped treatment was able to detect those who still had active TB disease, Paton tells Spotlight that further analysis of the sputum smears samples will be able to tell us more. The trial used a relatively low-technology approach where a symptom screening and a sputum smear test were used to determine if a participant still had active TB and needed to be re-treated.
“We need to run additional biomarkers, interrogate the data set in more detail to figure out who was cured, who wasn’t cured, over what duration and how well do these other things [sputum smear test and symptom screening] pick it [TB] up,” he says.
He adds that this was a starting point, “but we are likely to be able to do better if we use some of the new biomarker technologies for monitoring”.
Implications of findings
“These results are very exciting as proof of concept – they show it’s possible to shorten treatment for drug-sensitive TB even further,” says Lindsay McKenna, TB Project Co-Director at New York-based Treatment Action Group (TAG). “But we need to optimise the regimen and study this treatment strategy in broader populations, including people living with HIV – none were enrolled in the study – and [in] programme contexts,” she says.
“There are other trials that are being planned that look to proactively (for example, at time of treatment initiation) determine who might benefit from shorter versus longer treatment based on available indicators or risk factors known to be correlated with treatment outcomes, such as disease severity, BMI, and HIV status (called a stratified medicine approach), and to tailor the duration of treatment accordingly,” she adds. “If the latter stratified medicine approach is proven, it will be very interesting to see how these two approaches compare and are viewed by programmes and affected communities.”
Feasibility of shortened regimens
Nerissa Donato the site co-investigator for the Truncate TB trial from the Lung Centre in the Philippines outlined the feasibility and acceptability of the TRUNCATE strategy at last week’s conference. This was based on participant questionnaires, clinician surveys, description data from the trial, and observations from Donato.
“The TRUNCATE strategies were acceptable and feasible in the context of the clinical trial. It can be successfully implemented provided that it is supported by the NTP (national treatment programme) and embraced by trained clinicians,” she says.
She explains the main challenges to implementing the strategy were patients’ concerns about potential side effects and the greater pill burden, but after some discussion participants were comfortable with the regimen due to the possibility of a much shorter treatment regimen. The close following up of participants and follow-up visits required was different from the normal procedure of treating for six months and being discharged from care. But she says participants were generally happy to come back for the follow-up visits.
Clinicians who participated were initially sceptical of whether the regimen was safe and would work but after the trial, they had a more positive view, according to Donato.
She says that in order to implement the strategy in the real world, it would need to be adopted by the NTPs, which will likely require more data on cost-effectiveness.
Need better treatment approaches and regimens
Paton tells Spotlight that somewhere between the two extremes of overtreating TB patients and personalised medicine as seen in high-income countries, there can lie a better treatment option for TB patients. An approach that is less monolithic and instead based on reacting to individual patient needs and responses.
“We need to look at how do we personalise it [TB treatment], but in a way that’s not so high tech so it becomes impossible for programmes,” he says. “At least if you’re monitoring [patients] you’ve got a safety net. If you get it wrong, you just make sure you pick the person up early and re-treat and there shouldn’t be serious harm from that.”
Additional data from the trial will be released in the coming months.
