A massive global study has ranked the best and safest treatments for chronic hives when antihistamines fall short. The findings provide a clear treatment roadmap for both patients and clinicians alike.
Redness, swelling and intensely itchy wheals – those are the hallmark symptoms of urticaria, commonly known as hives. If symptoms persist for six weeks or more, the condition is considered chronic. When antihistamines, the standard first-line treatment, fail to provide relief, systemic therapies that work throughout the body are the next step.
A new large, international study, led by McMaster University in Canada, has comprehensively compared the safety and effectiveness of drugs and immunotherapies for chronic urticaria. The findings eliminate the guesswork in finding an appropriate – and, importantly, effective – treatment.
“This first comprehensive analysis of all advanced treatment options for chronic urticaria provides a clear and evidence-based ‘menu of treatment options’ for patients and their clinicians to choose from,” said corresponding author Derek Chu, MD, PhD, an assistant professor in McMaster’s Department of Medicine.
The researchers analyzed data from 93 studies and 11,398 participants, primarily adolescents and adults with moderate to severe symptoms of chronic urticaria. Only randomized controlled trials for systemic treatments were included; trials for antihistamines, steroids, and alternative medicines were excluded.
The researchers used a systematic review and Bayesian network meta-analysis (BNMA), a statistical technique that enables researchers to compare multiple interventions that may not have been directly compared in previous studies. They particularly examined outcomes important to patients, including urticaria activity (itch and wheal severity), angioedema (swelling) severity, quality of life, and treatment-related adverse events. Each study was reviewed for quality and risk of bias, and the certainty of evidence was rated as high, moderate, low and very low using the GRADE approach.
Ranked with a high certainty of evidence, the most effective treatments, showing the strongest and most consistent benefit across all patient outcomes, were omalizumab (Xolair, 300 mg every four weeks) and remibrutinib. Omalizumab is an injectable monoclonal antibody medication that works by blocking the action of immunoglobulin E (IgE), a substance that plays a critical role in allergic reactions and inflammation. Remibrutinib is an oral medication that inhibits Bruton’s tyrosine kinase (BTK), blocking a specific pathway involved in the release of histamine and other inflammatory mediators that cause chronic urticaria symptoms. Although it's not yet commercially available, it has demonstrated positive results in Phase 3 clinical trials and may soon be an important treatment option.
Dupilumab (Dupixent) is another injectable immunotherapy, a monoclonal antibody that blocks two specific proteins in the immune system, interleukin-4 (IL-4) and interleukin-13 (IL-13), that contribute to inflammation. The researchers found that it was likely effective for reducing the severity of itch and wheals, but its impact on swelling and overall quality of life was uncertain due to a lack of data. An immunosuppressive medication, cyclosporine, designed to dampen the immune-system-driven inflammatory response, may have been among the most effective medications for reducing itch and wheals, but also among the most harmful. It had higher rates of side effects, including kidney toxicity and high blood pressure.
The study had some limitations. Most trials were short-term, making it hard to assess the long-term safety of some drugs, and many of the older, cheaper drugs assessed (like sulfasalazine, azathioprine, and methotrexate) had low or very low certainty of evidence ranking, mostly from small or non-randomized studies. Also, few studies reported on angioedema-related outcomes using standardized tools. Children were underrepresented, with only one trial including participants under 12, limiting guidance for pediatric urticaria, and there’s a lack of quality data comparing high-dose omalizumab against other treatments. Finally, no randomized controlled trials tested a combination of treatments, which may be used in real-world practice.
Nonetheless, the study is the most comprehensive evidence-based comparison to date of systemic treatments for chronic urticaria. Patients now have a clearer hierarchy of options beyond antihistamines, allowing for personalized treatment. Of course, additional practical considerations such as cost, needle phobia, and convenience need to be factored into the decision.
The study received funding from the American Academy of Allergy, Asthma and Immunology (AAAAI) and the American College of Allergy, Asthma and Immunology (ACAAI). It was published in The Journal of Allergy and Clinical Immunology.
Source: McMaster University