When I was a medical student shadowing doctors in Borneo, I noticed that follow-up consultations were extremely brief and almost solely focused on new symptoms or infections of concern. For example, for a patient who had just undergone appendicectomy, the follow-up questions were almost invariably: Have you been tolerating orally? Are you able to pass motion? Has the surgical site healed? 

A rare disease like hereditary angioedema (HAE) is extremely difficult to diagnose and treat with such a brief examination.

If the follow-up interview was uneventful, the physician would swiftly move on to the next patient. In all fairness, this hyper-brief style of consultations was born out of necessity: physicians in my hospital see much too many patients than their western counterparts; efficiency is therefore king. 

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What I notice missing, time and again, are any questions about a patient’s quality of life; not just whether a patient experiences pain here or there, but how that pain impacts their ability to carry out activities of daily living. There is a a type of unspoken rule, much to the discredit of the overwhelmed local healthcare system, that patients are lucky to be seen, lucky to be alive, and they should therefore get back to their daily labor as soon as possible; complaining is deeply frowned upon. 

Read more about HAE etiology

A silver lining of the pandemic the world experienced is that there has been a spotlight on intangible health outcomes like quality of life. During the worst of the pandemic, when the poor were unable to work, there was an unfortunate uptick of suicides, demonstrating in stark shades that being physically alive and relatively functional were by no means the only metrics by which we should measure well-being. The internal world, the psychological space, deserve as much attention as that which is visible. 

“Knowledge about quality of life is important for understanding the consequences of illness and treatment, and for medical decision-making across age groups and culture,” Haraldstad and colleagues wrote in Quality of Life Research. “There is a need for improvements in this field, and researchers should pay closer attention to methodological and conceptual issues when planning quality of life studies.” 

Novel Research and Quality of Life 

There has been a sea change in how clinicians approach the design of their trials. Although primary and secondary endpoints are largely dictated by the disease area under study, researchers are increasingly including another domain that deserves equal attention: impact on quality of life. 

Such was the approach taken by Soteres and colleagues in their investigation of the merits of berotralstat, a first-line, once-daily oral prophylactic drug for patients with HAE. In their paper published in the Journal of Allergy and Clinical Immunology, they focused their entire study on whether the reduction of disease and treatment burden translated into measurable improvements in quality of life. 

In the field of rare diseases, pharmaceutical companies regularly invest in novel drugs they hope have the potential to transform the therapeutic landscape of a disease category. Financial incentives aside, these drugs, which tend to target known pathological pathways in a novel way, are intended to help make the lives of patients better, to help them feel, as much as possible, like a normal member of society. 

In modern medicine, to borrow a phrase from the Declaration of Independence, we hold these truths to be self-evident: that even patients with chronic, incurable diseases should be able to live a life of dignity and purpose, and that our job as doctors is to support them in this endeavor. Patients are more than just pain points and the sum of their body parts; they are just like the rest of us, with dreams, hopes, fears, anxieties. Their psychological well-being matters. 

The Specifics of HAE

HAE is a devastating disease in which patients experience recurrent attacks of edema that can be debilitating. This of course plays in their minds as they make decisions about their education, work, and finances. The study of berotralstat is unique in that it measures quality of life for a total of 96 weeks—nearly 2 years. 

The minimally clinically important difference is a 6-point reduction in the total score of patients completing the Angioedema-Quality of Life questionnaire; a decrease in scores indicates improvements in quality of life. 

The research team reported that patients who were prescribed berotralstat at 150 mg experienced mean improvements that exceeded the minimally clinically important difference value from week 4 to 96 on a variety of parameters. In addition, the mean improvement in scores during the study period was apparent, regardless of whether patients experienced gastrointestinal adverse events during the first 24 weeks. Importantly, researchers reported improvements across critical domains: energy levels, nutrition, functioning, and emotional well-being. 

“Long-term prophylaxis with berotralstat led to sustained and clinically meaningful improvements in patient-reported quality of life across multiple subgroups, suggesting sustained reductions in disease and treatment burden,” Soteres and colleagues wrote. 

Read more about HAE treatments

This study represents a growing trend in clinical research in which researchers moved beyond clinical parameters such as prognosis and estimated survival to work toward improving the quality of life of patients in the here and now. It is vital that rare disease medicine sheds itself of the insidious fatalism that has become characteristic of many of the studies published. A more hopeful, inclusive, and empathetic approach will be a positive step for all the stakeholders involved. 


Soteres D, Lumry W, Magerl M, et al. Berotralstat improved quality of life through 96 weeks across multiple subgroups of patients with hereditary angioedema. J Allergy Clin Immunol. 2023;151:AB139. doi:10.1016/j.jaci.2022.12.434

Haraldstad K, Wahl A, Andenæs R, et al. A systematic review of quality of life research in medicine and health sciencesQual Life Res. 2019;28(10):2641-2650. doi:10.1007/s11136-019-02214-9