{"id":101895,"date":"2022-09-08T10:29:43","date_gmt":"2022-09-08T10:29:43","guid":{"rendered":"https:\/\/alj.com\/?post_type=perspective&p=101895"},"modified":"2022-11-15T05:18:51","modified_gmt":"2022-11-15T05:18:51","slug":"innovation-in-inflammation","status":"publish","type":"perspective","link":"https:\/\/alj.com\/en\/perspective\/innovation-in-inflammation\/","title":{"rendered":"Innovation in inflammation"},"content":{"rendered":"

Guest Author: Dr. Simba Gill, Chief Executive Officer, Evelo Biosciences<\/h4>\n

Inflammation has been called the silent killer.\u00a0 It is one of the main causes of diseases and conditions affecting billions of people all over the world.<\/p>\n

The list of inflammatory diseases includes everything from common conditions like asthma, Alzheimer\u2019s and allergies, to debilitating diseases like psoriasis, inflammatory bowel disease and neuroinflammatory diseases. \u00a0<\/p>\n

In addition, inflammation plays a key role in some of the world\u2019s leading causes of death, such as cancer, heart disease and diabetes. \u00a0Recent research has even suggested that the process of ageing itself, along with its associated pathologies, is driven by persistent inflammation<\/a>[1]<\/sup><\/a>.<\/p>\n

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Of course, every disease is different and affects patients in different ways.\u00a0 But all these diseases and conditions are characterized by systemic inflammation \u2013 and all have a considerable, negative impact on the lives of billions of people across the globe.<\/p>\n

Starting with the skin<\/h2>\n

Two of the most prevalent, chronic inflammatory diseases that cause pain for millions of patients are skin conditions: psoriasis and atopic dermatitis.\u00a0<\/p>\n

The US National Psoriasis Foundation defines psoriasis as \u201can immune-mediated disease that causes inflammation in the body\u201d.\u00a0<\/p>\n

It is driven by Th17 inflammation and typically results in the formation of thickened red plaques with scaling on the skin, particularly around the elbow, knees, scalp and lower back, which may itch, burn and sting. \u00a0<\/p>\n

\"Examples
While characterized as mild to moderate in terms of body surface area, individual Psoriasis lesions can be severe. Significant number of mild to moderate patients are not treated at all due to physician concern about long-term safety or tolerability, as well as efficacy, of currently available therapies.a Along with the cosmetic, emotional, and functional disease burden of psoriasis are comorbidities such as psoriatic arthritis, increased risk of depression, inflammatory bowel disease, & ischaemic heart disease.<\/figcaption><\/figure>\n

The World Health Organization\u2019s Global Report on Psoriasis[2]<\/a> estimates there are over 100 million people who suffer from psoriasis across the globe.\u00a0 Symptoms often start between the ages of 15 and 25 and affect men, women and children of all ethnic groups. \u00a0Inflammation caused by psoriasis can also affect other organs and tissues in the body.<\/p>\n

\"Atopic
Atopic dermatitis, or eczema, is a type of inflammatory skin disease that disrupts the skin barrier and its ability to hold moisture<\/figcaption><\/figure>\n

Atopic dermatitis, or eczema, is a type of inflammatory skin disease that disrupts the skin barrier and its ability to hold moisture. \u00a0According to the World Allergy Organization, it affects between 5%-30% of children and 1%-10% of adults globally[3]<\/sup><\/a>.\u00a0<\/p>\n

Characterized by dry, intensely itchy skin, atopic dermatitis affects people of all ages, but most often begins in infancy and early childhood, with some people suffering lifelong symptoms.\u00a0 Atopic dermatitis can also occur alongside other atopic diseases, such as food allergy, asthma, and allergic rhinitis, which are all associated with a Th2 inflammatory imbalance.<\/p>\n

Most psoriasis and atopic dermatitis patients are classed as having mild or moderate disease. \u00a0\u00a0In the United States, roughly 93% of psoriasis patients and 85% of atopic dermatitis patients have either mild or moderate disease, with similar distributions serious throughout the world. \u00a0The terms mild and moderate are misleading as these diseases have serious impacts on the lives of sufferers.<\/p>\n

Misleading labels<\/h2>\n

The disease severity labels of \u201cmild,\u201d \u201cmoderate,\u201d and \u201csevere\u201d are defined by how much of a patient\u2019s body is affected.\u00a0 They do not necessarily reflect the severity of the impact the condition has on the life of a patient.\u00a0 Even a \u201cmild\u201d psoriasis or atopic dermatitis diagnosis can be a serious condition.\u00a0 The lesions are often highly visible and can be painful, with cracked skin, bleeding, and persistent itchiness, often on very inconvenient areas of the body including hands, feet and the groin\/genital area. \u00a0\u00a0These can often impact sufferers\u2019 lives and livelihoods.<\/p>\n

People who suffer from psoriasis and atopic dermatitis report a significant impact on their quality of life and mental health.\u00a0 In one survey[4]<\/sup><\/a>, around 65% of patients with mild psoriasis said the diseases had a moderate to high impact on their daily life. \u00a0This has been estimated to be greater than the impact of diabetes, cardiovascular disease, and even some cancers.<\/p>\n

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It is an unfortunate truth that if you suffer from psoriasis or atopic dermatitis, you are more likely to suffer from co-morbidities, such as psoriatic arthritis, asthma or allergies, as well increased risk for adverse cardiovascular events.\u00a0 People with mild psoriasis or mild atopic dermatitis also have a higher risk of depression, psoriatic arthritis and metabolic syndrome than people who do not suffer from these diseases.\u00a0 Similarly, due its chronic nature and frequency of flare-ups, atopic dermatitis is associated with a substantial physical and mental health burden not only on patients themselves, but also their families.<\/p>\n

Imperfect treatment models<\/h2>\n
\"Evelo
Valeria Kravitz, Scientist, Microbiology in Evelo\u2019s labs in Cambridge, MA, USA<\/figcaption><\/figure>\n

Despite the global prevalence of these diseases and the significant impact they have on millions of lives, current treatment options are far from ideal.\u00a0 Patients with mild or moderate psoriasis or atopic dermatitis are usually treated with topical medications- treatments applied directly to the skin in the locations where symptoms occur.\u00a0 These are often inconvenient, awkward and time-consuming to apply, which leads to poor adherence and reduced effectiveness.\u00a0 Importantly topical treatments have no effect on the significant disease effects inside the body.<\/p>\n

Other than topical medications, treatments are limited.\u00a0 For patients with severe symptoms, treatments like injectable antibody therapies or systemic immunosuppressants may be available, but these options are generally not accessible, or suitable, for those with mild or moderate disease \u2013 which is most sufferers.\u00a0 Not to mention the high costs and in some cases tolerability issues, such as gastro-intestinal problems, that are often involved in accessing these types of treatment options.<\/p>\n

Even for those suffering from moderate to severe symptoms, the segment where most novel systemic therapies are approved, factors including safety, convenience, and high cost mean these treatments are not accessible for many people. \u00a0<\/p>\n

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In the US, for example, innovative psoriasis and atopic dermatitis products can cost between US$ 40,000 and US$ 80,000 per person, per year. \u00a0The high cost is one of the reasons why, even in the US, where access to innovative therapies is much higher than other regions of the world, it is estimated that less than 8% of patients with psoriasis and less than 2% of patients with atopic dermatitis have received these treatments, while approximately 50% of psoriasis and atopic dermatitis patients are not treated with any prescription therapy. \u00a0Outside the US, even fewer patients have access to these medicines.\u00a0<\/p>\n

Responding to the needs of patients<\/h2>\n

Topical therapies have long been the default treatment option for psoriasis and atopic dermatitis sufferers.\u00a0 But even if these treatments are applied regularly and effectively, the fact remains that they only treat the superficial skin symptoms of these diseases, while leaving untreated the underlying systemic inflammation that characterizes these conditions.\u00a0<\/p>\n

Oral immunosuppressants do address this systemic inflammation, but often at the cost of issues around safety concerns, monitoring requirements, and tolerability issues, including diarrhea and nausea. \u00a0Similarly, the use of injectable antibody therapies, the other main treatment option especially for moderate and severe cases, is limited by factors including the need to administer by injection, the potential for immunosuppression, and the high costs involved, as outlined above.<\/p>\n