Patients Insights - The road to Dupilumab: a case study on atopic dermatitis

Welcome to the Patients Insights series, a blog from mama health where we delve into the lived experiences of patients with chronic illnesses. Here you can find out how our analytical product offers a window into the patient journey, informed directly by thousands of patient narratives through the technology of process mining.

In this article, we focus on how patients’ journey can lead to advanced treatments, specifically Dupilumab, a monoclonal antibody-blocking treatment. While the medication can be prescribed for multiple diseases, the article focuses on individuals with Atopic Dermatitis (AD), a special type of eczema, a chronic skin condition characterized by periodic dry, itchy, and inflamed skin.

Disclaimer: In this article, the running example and figures are based on synthetically generated data emulating patients with AD. Contact mama health if you are interested in real journey insights.

One illness, different severities

Atopic dermatitis (AD) is a chronic condition often emerging in early infancy and childhood with 85% diagnosed before the age of 5? . Its symptoms typically diminish with age, yet approximately 2 to 10% of patients continue to experience them during adulthood? . Figure 1 represents the complexity of the patient journey in managing Atopic Dermatitis (AD), depicting various pathways that include frequent visits to doctors, experiencing different levels of disease severity, utilizing diverse medications, and changing environmental factors in daily life. Managing AD involves a continuous effort to identify and mitigate triggers while seeking effective soothing strategies. Although the exact cause of atopic dermatitis remains elusive, researchers acknowledge the combined influence of genetics, the immune system, and environmental factors in its development? . mama health is capturing the lived experience of patients across the entire spectrum of doctor visits, treatments and alternative solutions to make sense of this complexity that is still eluding research. Utilizing process mining techniques in this longitudinal view can pinpoint inefficient routes and decisions that are informed directly by thousands of patients. It can highlight factors commonly associated with 'Mild' and ‘Severe’ stages of the disease, but also inform on the best course of action to recover from severe symptoms. Such insights are valuable for both patients and healthcare providers, guiding them towards treatments and alternative approaches most likely to be beneficial. While treatment plans must be tailored by medical professionals to suit the unique needs and conditions of each patient, analyzing patient journeys on a larger scale can inform upon general trends, prevalent challenges, and successful methods in managing and recovering from the disease.

Treatment of last resort

Dupilumab, sold under the brand name Dupixent, represents a significant advancement in the treatment of Atopic Dermatitis (AD), particularly for patients who have found limited success with traditional therapies. It is prescribed to patients with moderate AD, when other treatments have not helped, and severe AD. The medication has been authorized in the last years to treat children with severe AD as young as 6 months. As a monoclonal antibody, it specifically targets the underlying inflammatory processes that drive AD, offering a novel approach compared to conventional treatments. This medication is often prescribed when other therapies, such as topical corticosteroids or other systemic immunosuppressants, have failed to provide adequate relief (see Figure 2). Dupilumab's mechanism of action, inhibiting the activity of key proteins involved in the inflammatory pathway, makes it a valuable option for those with moderate to severe AD.

Hurdles in treatment access

Managing chronic diseases differs from the treatment of short-term illnesses. While acute conditions are usually straightforward to diagnose and treat, chronic diseases often require a longer and more complex journey to find effective treatments that improve quality of life.

One significant factor in managing chronic diseases is the delay in patients adopting the right lifestyle habits and treatments. This delay can make the illness worse over time. For example, a 32-year-old woman shares in a testimony how she didn't get proper advice on managing her condition until two decades into her illness, which likely worsened her condition? .

Even when patients could benefit from advanced treatments, there's often a gap to these therapies. For instance, pediatricians, who often see young patients first, tend to prescribe simpler treatments, which may not be enough for more advanced cases (see Figure 3). This delay in using advanced treatments or referring to specialists can worsen the condition. This difference in prescribing behavior is concerning because advanced treatments that have become available in recent years could significantly improve patient outcomes.? Overall in 2022, there were globally 223 million people living with atopic dermatitis, around 43 million aged between 1 and 4? . Of them 10 to 15% are diagnosed with severe AD and could thus be candidates for new systemic therapies. Our analysis shows that patients often don't receive these treatments until they've had the illness for many years, 32 years on average. Recommending advanced treatments earlier could help patients and their caregivers and reduce the long-term impact of the disease on their lives.

To address these delays, it's essential to educate both patients and doctors about the importance of early and appropriate management, including when to seek specialized care. Raising awareness about the latest treatments and encouraging a proactive approach to managing chronic conditions can ensure that patients get the care they need sooner.

Factors of treatment success

Dupilumab has marked a significant advancement in the treatment of atopic dermatitis (AD), offering substantial relief to many patients. However, it's important to recognize that this treatment does not work universally for all individuals with AD. Some patients discontinue the treatment prematurely, either due to adverse effects like conjunctivitis or because they don't perceive quick results — the treatment may take 3 to 6 months to manifest effects. Treatment efficacy is highly dependent on treatment regimen. Research involving various dosages, ranging from 50mg to 300mg and administered at intervals from weekly to monthly, underscores this point ?? ,? ? and similarly questions on dose reduction and interval spacing are still being investigated ??? , ?? , ?? ?. Therefore, tailoring the treatment plan to individual? patient? needs is vital for optimal outcomes.

Currently, the regimen is based on age class and weight?? , but any individual above 18 follows the same regimen regardless of sex, age, comorbidity or EASI score which may affect their perceived efficacy (see Figure 4). Specifically for adolescents, the dosage depends on the weight class, so following the guidelines: a 17 year old weighing 55kg would increase the dosage by half the amount just by turning 18. This follows a general trend in pharmaceutical research that doesn’t take into account that each body is unique and cannot be administered the same amount of a drug. A man in his late 70 with diabetes will react differently than an asthmatic woman in her twenties. Researchers?? point out that they are gender differences in the immune response that are not being considered in clinical research, and that women in general are underrepresented in clinical studies.? Our tool enables us to exactly identify how the perceived efficacy of a drug differs from the general patient population, depending on physiological, demographic and disease specific factors.

Figure 4 emphasizes the changes in drug results when gender, comorbidity and AD severity are considered. Analyzing data from thousands of patient experiences is key in understanding the reasons behind treatment failures in certain cases. This approach can enhance the likelihood of success and clarify why there's often a discrepancy between ideal, planned, and actual drug usage, steering us towards more tailored, personalized and effective healthcare solutions.

If Dupi doesn't work, what else?

Fortunately, the medical field is not devoid of alternatives. Other treatments available in the market have shown promising results, with some even surpassing the efficacy of Dupilumab at certain dosages ??? , ?? , ?? , ?? ) . Moreover, the landscape of AD treatment is rapidly evolving, with approximately 15 new drugs undergoing clinical trials as of 2022? . These emerging therapies, expected to be introduced in the coming years, hold the potential to further enhance the quality of life for patients with AD, broadening the spectrum of effective treatment options. Most recently, Lebrikinumab by Almirall and Eli-Lilly got approved?? by the European Commission and should hit the market in the near future?? .?

Staying close to the patients and evaluating trends in patient care is a vital step in this process. Our product line enables us to conduct thorough investigations on international or regional differences in patient journeys as well as treatment intake, adherence and satisfaction in order to closely understand factors affecting the care of chronic illnesses. It allows us to consider factors of health that are being overlooked in current research, but which are detrimental to the success of disease management and which will pave the way towards more personalized medical care.