Researchers from ten different countries reported the successful completion of the third phase of clinical trials for gefurolimab, a drug designed to treat generalized myasthenia associated with acetylcholine receptor antibodies. This drug works by blocking the activation of the C5 complement component, which led to a reduction in disease symptoms and an increase in patients' daily activity levels.
Myasthenia is a chronic autoimmune disease affecting the neuromuscular system. It is characterized by gradual weakness and rapid fatigue of the striated skeletal muscles. In approximately 85% of patients with the generalized form, autoantibodies against postsynaptic nicotinic acetylcholine receptors are found at the nerve-muscle junction. These antibodies trigger the activation of the complement system and the formation of a membrane attack complex, which damages the postsynaptic muscle membranes, disrupting nerve impulse transmission.
Existing treatment methods include the use of C5 complement component inhibitors (such as eculizumab, ravulizumab, and zilucoplan), neonatal Fc receptor inhibitors (efgartigimod and rozanolixizumab), as well as cytotoxic antibodies against the CD19 antigen of B lymphocytes and plasma cells (inebilizumab).
Gefurolimab is a nanobody type drug consisting of two high-affinity heavy chain immunoglobulin domains: an N-terminal anti-albumin domain, which serves to prolong systemic circulation and improve pharmacokinetics, and a C-terminal anti-C5 domain, connected by a flexible linker. Its function is to block C5 activation by inhibiting its enzymatic cleavage. The drug is administered via subcutaneous injection once a week to patients.
Annane Djillali from the University of Paris-Saclay, together with colleagues and subsidiary AstraZeneca company, Alexion, conducted a double-blind randomized controlled Phase III trial named PREVAIL. The study was carried out in 113 clinical centers across 20 countries and involved 260 adult patients (mean age 52.8 years; 60.4% female) with generalized myasthenia (MGFA classes II–IV, five or more points on MG-ADL) and acetylcholine receptor antibodies.
Patients were randomly assigned: half received gefurolimab (initial dose 600 or 900 mg, maintenance 300 or 600 mg) via weekly subcutaneous injections, while the other group received placebo. Additional rescue therapy was permitted if clinically significant deterioration occurred. In total, 249 participants completed the full 26-week course.
According to the study results, the average reduction in symptoms on the MG-ADL scale was -4.2 points in those taking the active drug, compared to -2.6 points in the placebo group (a difference of -1.6 points; p < 0.001). A similar improvement was recorded on the QMG scale: -4.5 points versus -2.4 points (a difference of -2.1 points; p < 0.001). Improvement became noticeable within one week after the first injection. By the sixteenth week of treatment, 65.5% of patients receiving the drug achieved a symptom reduction of three or more points on the MG-ADL, compared to 52.2% in the placebo group (odds ratio 1.74; p = 0.04). Furthermore, 46.3% of patients on the drug achieved a reduction of five or more points on the QMG, whereas this figure was 25.2% in the placebo group (odds ratio 2.56; p = 0.002).
The incidence of adverse events was similar in both groups. The most common side effects when using gefurolimab included injection site reactions, headache, back pain, and nasopharyngitis. The overall conclusions of the third phase of the trials confirm that weekly injections of gefurolimab provide both early and sustained clinical improvement in patients with generalized myasthenia and acetylcholine receptor antibodies at acceptable tolerability.
It is also worth noting that in 2024, Chinese scientists published a report on the success of the third phase trials of the monoclonal antibody batoclimab, which targets the neonatal Fc receptor. This drug demonstrated a significant reduction in myasthenia severity according to the MG-ADL and QMG scales compared to placebo. The side effects of this drug were predominantly upper and lower respiratory tract infections, as well as peripheral edema.
In South Africa, there is a problem where thousands of people live with viral hepatitis without realizing they are infected. World Hepatitis Day is observed annually on July 28th, drawing attention to one of the deadliest infectious diseases that often goes unnoticed for years.
The condition is a serious concern because it can put people at risk of developing severe liver disease, liver cancer, and premature death. The main difficulty is that hepatitis often progresses without symptoms or with minimal signs before significant liver damage occurs.
Hepatitis is defined as inflammation of the liver. Although it can be caused by alcohol consumption, certain medications, or autoimmune diseases, viral hepatitis remains the most common cause worldwide. There are five main types of hepatitis viruses: A, B, C, D, and E. Hepatitis B and C are responsible for the vast majority of serious cases and deaths because they can cause chronic infections.
According to the World Health Organization (WHO), viral hepatitis causes approximately 1.3 million deaths globally each year, comparable to the number of deaths from tuberculosis. One reason for the danger of hepatitis is that it is often called a 'silent disease.' Many people infected with hepatitis B or C may feel completely healthy for many years while the virus slowly damages the liver.
When symptoms do appear, they can include fatigue, fever, nausea or vomiting, loss of appetite, dark urine, pale stools, jaundice (yellowing of the skin and eyes), and abdominal pain. By the time these signs appear, liver damage may already be in an advanced stage.
South Africans continue to bear the burden of viral hepatitis, especially hepatitis B. In 1995, the country included hepatitis B vaccination in the childhood immunization program, which significantly reduced infection rates among the younger generation. Nevertheless, many adults born before the vaccine became regularly available remain at high risk. Public health experts suggest that hundreds of thousands of South Africans suffer from chronic hepatitis B, many of whom have never been tested or diagnosed. Although hepatitis C is less common than hepatitis B, it remains a problem in the general population. With early diagnosis, hepatitis C is now curable with modern antiviral drugs.
Different hepatitis viruses are transmitted through different routes. Hepatitis A and E are usually transmitted through contaminated food or water and typically cause a short-term illness. Hepatitis B is transmitted through contact with infected blood and body fluids. This can happen through unprotected sexual intercourse, sharing needles or syringes, mother-to-child transmission during childbirth, and unsafe medical or cosmetic procedures using non-sterile equipment. Hepatitis C is primarily transmitted through blood-to-blood contact, including sharing injection equipment, and less frequently through unsafe medical procedures. It is important to note that viruses are not transmitted through casual contact, such as hugging, sharing food, coughing, or sneezing.
Healthcare workers advise testing individuals who were born before routine hepatitis B vaccination was introduced, have a relative suffering from hepatitis B, have had multiple sexual partners, use drugs intravenously or previously shared needles, have received blood transfusions or certain medical procedures before improved screening methods were implemented, live with HIV, and work in medical facilities with potential blood exposure. Furthermore, pregnant women are regularly screened for hepatitis B in many medical institutions to reduce the risk of transmitting the virus to the infant.
The good news is that viral hepatitis can be prevented and, in some cases, cured. Vaccines are available for hepatitis A and hepatitis B, with hepatitis B vaccination included in South Africa's Expanded Immunization Program. Currently, there are no vaccines for hepatitis C, but highly effective direct antiviral drugs can cure over 95% of infections if treatment starts in time. For people living with chronic hepatitis B, antiviral therapy can suppress the virus, reduce liver damage, and lower the risk of liver cancer. Simple blood tests allow for the diagnosis of hepatitis, giving patients the opportunity for monitoring or treatment before complications develop.
German scientists studied the long-term effectiveness of various blood-based biomarkers for predicting the development of Alzheimer's disease. They concluded that beta-amyloid folding disruption has the highest prognostic value, and its effectiveness increases when used in combination with other biomarkers.
Since existing disease-modifying drugs only work in the early stages or with mild cognitive impairment, it is critically important to diagnose the disease at the earliest possible, preferably preclinical, stages. However, many developed methods, such as measuring the ratio of beta-amyloid fragments 42/40 in cerebrospinal fluid or PET/CT scans of beta-amyloid deposits in the brain, are expensive, technically complex, and invasive. Therefore, particular attention is paid to diagnosis via blood tests.
In 2025, the U.S. Food and Drug Administration (FDA) approved the first blood test based on determining plasma concentrations of phosphorylated tau protein 217 (p-tau217) and beta-amyloid 1-42. It is important to note that all mentioned methods are only applicable when cognitive impairment is present and do not allow for preclinical diagnosis of Alzheimer's disease.
Hermann Brenner from Heidelberg University, along with colleagues, analyzed data from 779 individuals participating in the prospective ESTHER cohort. These participants, mostly women (52–57%), were over 61 years old at the start of the study. The researchers studied levels of p-tau217, light chain neurofilament (NfL), and glial fibrillary acidic protein (GFAP) in the blood at baseline and compared their prognostic power with beta-amyloid folding disruption, as well as with previously measured p-tau181 levels. The observation period lasted from 9.7 to 16.7 years (median was 13.6 years).
During the follow-up, any form of dementia developed in 385 participants, including Alzheimer's disease in 122 people. It was found that baseline p-tau217 levels were significantly higher in people with any dementia, and especially in patients with Alzheimer's disease (p < 0.0001), with this dependence being dose-proportional. Nevertheless, this correlation was strongly expressed only during the first nine years and was weaker than the association with GFAP (the risk ratio per standard deviation increase was 1.58 for p-tau217 versus 1.95 for GFAP in a multivariate model). In later follow-up stages (9–17 years), associations between p-tau217, GFAP, and NfL levels with the risk of any type of dementia were absent; however, the risk of Alzheimer's disease remained only for p-tau217 and GFAP, but significantly attenuated compared to the first nine years.
The Area Under the ROC Curve for diagnosing any dementia using p-tau217 was 0.688 in the first nine years, decreasing to 0.599 later, which performed better than p-tau181 (p < 0.0001). For GFAP and NfL, this metric reached 0.743 and 0.733 respectively in the first nine years. Clinical accuracy is generally considered sufficient at a level of 0.8 and above. When diagnosing Alzheimer's disease, the area under the ROC curve was higher for all tested biomarkers, but also noticeably dropped after nine years (to 0.656 for p-tau217). The combination of all three biomarkers demonstrated a level of 0.842 in the first nine years and 0.703 in subsequent years.
To directly compare the prognostic effectiveness of p-tau217 and beta-amyloid folding disruption, the authors conducted an analysis in a subgroup where measurements of both markers were available (180 individuals without dementia and 55 with Alzheimer's disease). In the first nine years, their effectiveness was similar (AUC of 0.734 and 0.752). However, beta-amyloid folding disruption showed significantly higher effectiveness in the preclinical stage (upon developing Alzheimer's disease within 9–17 years: 0.847 vs 0.586) and throughout the entire observation period (0.794 vs 0.670). The highest results were achieved by combining beta-amyloid folding disruption with all other biomarkers (0.820 in the first nine years, 0.924 in subsequent years, and 0.858 over the entire observation period). Adding demographic and genetic factors (age, sex, BMI, and APOE ε4 carrier status) improved diagnostic accuracy in the prodromal phase (up to 0.894 in the first nine years), but had less impact on subsequent years and the overall observation period.
Thus, although p-tau217, GFAP, and NfL showed high effectiveness in detecting dementia, especially p-tau217 in Alzheimer's disease, this effectiveness was limited to the initial years of observation. Beta-amyloid folding disruption is recognized as the best preclinical predictor of Alzheimer's disease, especially when combined with all other biomarkers.
Previously, another international scientific group analyzed data from 462 individuals and found that the highest levels of p-tau217 are observed in newborns, especially premature ones, and can be almost three times higher than in Alzheimer's disease, although they then decrease to young adult levels within the first month of life. This indicates that tau phosphorylation performs different functions at different stages of central nervous system development.
It is also worth mentioning that researchers from ten countries reported the successful completion of the third phase of clinical trials for the drug gefurunlimab for treating generalized myasthenia gravis with acetylcholine receptor antibodies. This drug works by blocking the activation of complement component C5, and during the trials, it helped patients reduce symptoms and increase daily activity. This was reported in the journal JAMA Neurology.
Patients suffering from Crohn's disease show an increased frequency of postoperative complications in the artificial joint area, known as periprosthetic infections. According to the study data, this risk increases by an average of 38 percent. It is important to note that ulcerative colitis did not demonstrate an influence on the probability of adverse outcomes.
Inflammatory bowel diseases, including Crohn's disease and ulcerative colitis, have become much more common in recent decades. These conditions are associated with impaired immune regulation in the digestive tract. In addition to GI problems, both pathologies often manifest with extraintestinal symptoms. For example, bone mineralization deficiency affects the musculoskeletal system, increasing the danger of fractures. Furthermore, people with inflammatory bowel diseases often face degenerative changes in their joints, which may require total endoprosthesis.
There is uncertainty regarding the level of risk of postoperative complications following such interventions in this group of patients. It was noted that microbiome disturbances characteristic of inflammatory bowel diseases can increase the likelihood of infections at surgical sites. Additionally, immunological disorders and the use of immunomodulatory drugs, which are usually prescribed for treating these diseases, may contribute to an increased risk of infectious complications after joint surgery.
A team of scientists led by Nathaniel Heckmann from the University of Southern California conducted a study on the link between inflammatory bowel diseases and the risk of periprosthetic infection—a complication after joint endoprosthesis. The researchers used a large national representative database. Their goal was to establish a correlation between these diseases and infection within 90 days after elective hip or knee joint endoprosthesis.
The study included 10,040 patients scheduled for hip or knee endoprosthesis who had a history of inflammatory bowel diseases. Among them, 54.64 percent had Crohn's disease, and 45.36 percent had ulcerative colitis. These patients were compared with a control group of 70,203 individuals. Specifically, 5,474 patients with Crohn's disease were matched with 38,230 control patients, and 4,555 patients with ulcerative colitis were matched with 31,865 control patients.
Univariate regression analysis showed that within 90 days after surgery, the incidence of periprosthetic infection in patients with inflammatory bowel diseases was similar to the control group (0.71 percent versus 0.61 percent; p = 0.245). However, a sub-analysis revealed that in patients with Crohn's disease, the rate of periprosthetic infection was higher than in the control group (0.86 percent versus 0.62 percent; p = 0.043). No such association was found in the case of ulcerative colitis (0.53 percent versus 0.64 percent; p = 0.365).
After applying multivariate models adjusted for confounding factors, a statistically significant increased frequency remained in patients with Crohn's disease. The results of this study emphasize the need for pre-operative risk stratification and optimization of treatment for patients with Crohn's disease requiring joint endoprosthesis. Scientists plan to continue research to determine the biological and mechanistic basis of the identified relationship. It is also mentioned that a diet restricting daily caloric intake to 1090 kilocalories can effectively reduce the activity of Crohn's disease, which could potentially help prevent increased infection risk.
