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The recent approval of ruxolitinib in the UK and EU has marked an important step forward in the treatment of vitiligo, but there’s still a long way to go to ensure timely and effective treatments for all. Dr Viktoria Eleftheriadou, consultant dermatologist and associate professor of dermatology, speaks to Rod Tucker about the recent developments and future trajectory.
Dr Viktoria Eleftheriadou is a consultant dermatologist at Walsall Healthcare NHS Trust and The Royal Wolverhampton NHS Trust and associate professor of dermatology at the University of Birmingham. She completed a PhD on vitiligo at the University of Nottingham, and now splits her time between clinical and research responsibilities.
One of her current focuses is running a specialist vitiligo clinic for adults and children, receiving referrals from both GPs and other secondary care centres. While her primary role in these clinics is the clinical management of patients, it also allows her to recruit participants for many of the clinical trials that she is involved with as part of her research role.
Understanding vitiligo
Vitiligo is an autoimmune skin disorder in which the immune system attacks melanocytes, leading to a loss of skin colour. The condition can either affect just one side of the body, which is termed segmental vitiligo, or both sides, which is known as non-segmental vitiligo. This distinction, Dr Eleftheriadou explains, is related to both disease progression and its response to treatment.
‘Segmental disease seems to develop earlier in kids or adolescents and doesn’t seem to progress once it has affected that segment of the skin,’ she says. ‘Non-segmental does spread to other areas of the body and can sometimes spread extensively, where we call vitiligo generalised, with lots of patches.’
Vitiligo can affect anyone. There are no differences between ethnicities or the sexes, and it can develop at any age, though as Dr Eleftheriadou clarifies, ‘about 80 per cent of patients will have developed the condition before the age of 30, and 50 per cent before the age of 20’. As a result, the vast majority of sufferers are a younger and generally otherwise healthy cohort. The impact of the condition can be devastating, particularly, Dr Eleftheriadou says, for those with darker skin tones due to an association with social stigmatisation.
Moreover, vitiligo also becomes much more visible during the summer months when individuals have more sun exposure. While darker skin tones may afford greater protection against the effects of UV radiation, this protection is lost in areas affected by vitiligo. Consequently, sufferers easily burn in these areas and therefore require additional protective suncream or clothing to shield their skin during warmer weather, which can be seen by some to be an additional burden.
The causes of vitiligo
The underlying cause of vitiligo remains uncertain. Dr Eleftheriadou highlights that it is probably linked to genetics, although unearthing the responsible genes is challenging. ‘There is a combination of 50 different genes which can lead to the development of vitiligo, which makes everything very complicated,’ she says. ‘Unfortunately there isn’t a single gene identified for vitiligo that we could work on.’
As well as genetics, some environmental influences play a role, in particular stress or stress-related factors, and Dr Eleftheriadou says that ‘many of my patients say that they first developed vitiligo because of a stressful event in their lives’. While an obvious factor in adults, this is less likely to account for its development in children. She believes that the cause ‘is probably a combination of genetic factors as well as environmental factors’.
Since vitiligo is an autoimmune disease, sufferers are also at a greater risk of developing other autoimmune disorders. One study from 2020, for example, found that having vitiligo was associated with a 65% higher prevalence of hypothyroidism, although risk was also elevated for other conditions such as rheumatoid arthritis and multiple sclerosis.
Addressing unmet needs
Dr Eleftheriadou feels that the greatest unmet need for vitiligo is the lack of effective treatments. As the lead author for the British Association of Dermatologists 2022 guidelines on the management of vitiligo, she noted, ‘currently, the treatments that we have are being used off-license, for example, topical corticosteroids and topical calcineurin inhibitors’.
Topical treatments are only really suited to those with limited disease and are not appropriate for patients with more extensive vitiligo. ‘Currently for these patients we have phototherapy combined with oral steroids or topical creams, but only about 30-40% will improve and the others will not, even after months of treatment’.
Indeed, this is a further and frustrating problem for dermatologists: the current impossibility to predict whether or not a particular treatment will be effective. What’s more, most therapies need to be used for at least three to four months before patients may start to experience a response.
Equally essential yet largely unmet, is the lack of psychological support for those with vitiligo. While there is a general recognition that in the UK, mental health services are severely overstretched, a large body of research has identified the huge psychological burden experienced by those with vitiligo. In trying to address this, Dr Eleftheriadou is currently working with psychologists to help create a psychological support package for people with the condition.
The approval of ruxolitinib
The approval of ruxolitinib by the European Medicines Agency in April 2023 and by the by the UK’s Medicines and Healthcare products Regulatory Agency in July 2023, following a similar approval in the US, is a critically important development for the treatment of vitiligo.
As a Janus kinase (JAK) inhibitor, ruxolitinib disrupts cytokine and growth factor signalling and ultimately produces an anti-inflammatory effect. But just how it works in vitiligo remains unclear. Studies have focused on using the drug in non-segmental vitiligo largely because ‘segmental disease is often resistant to treatment with drugs such as topical corticosteroids and therefore many of the trials exclude segmental vitiligo because it doesn’t react as well to treatment’, Dr Eleftheriadou explains. This reflects what she finds in clinical practice.
The approval of ruxolitinib was based on the findings of two identical, randomised, double-blind placebo-controlled, phase 3 trials, TRuE-V1 and TRuE-V2, which were published in a single paper in the New England Journal of Medicine. The findings in the two trials were broadly similar, with around 30% of patients assigned to ruxolitinib achieving a 75% improvement in facial vitiligo following 24 weeks of treatment.
While this might seem like a long, drawn-out affair, Dr Eleftheriadou clarifies that this is not unusual. ‘Any treatment will have to be applied for at least three to four months to see any improvement, and if we see an improvement in clinical practice, the treatment is continued and there are often much better results after nine to 12 months,’ she says.
In fact, Incyte, the manufacturer of ruxolitinib, undertook an open-label extension trial of the two TRuE trials and, while yet to be published in full, a conference abstract available from the manufacturer suggests that many patients to achieved a high level of facial re-pigmentation sustained a durable response for 12 months after stopping treatment.
Future management of vitiligo
Although ruxolitinib is the first treatment approved for vitiligo, Dr Eleftheriadou feels there is a need for more topical, oral and even injectable therapies, particularly for those who have extensive disease.
‘In some cases, vitiligo can progress quite fast so by the time a patient has been diagnosed and waits to see a dermatologist, which might take months, it is too late to start applying creams,’ she says. Fortunately, it seems that the introduction of ruxolitinib is just the start of improvements to treatment options as there are at least five other JAK inhibitors being investigated as potential treatments for vitiligo.
Dr Eleftheriadou welcomes these innovations, which she says are testament to the recognition that, ‘vitiligo is actually a disease and not simply a cosmetic disorder’. She senses that vitiligo is at the same stage now as psoriasis was 10 years ago, and there is wide range of different therapies available for psoriasis today.
Despite the approval of ruxolitinib and potential for further treatments, Dr Eleftheriadou feels that a continuing problem is how patients with vitiligo are still not being treated early enough. In her recent study presented at the British Association of Dermatologists conference, she examined the primary care management of the disease, which was found to be largely unsatisfactory.
The study revealed that in the first year following their diagnosis, 61% of patients did not receive any vitiligo-related treatment, and this figure increased to 82% from the second year onwards. It was also clear, says Dr Eleftheriadou, that patients were often started on antidepressants, suggesting that related symptoms were being treated rather than addressing the underlying condition.
As such, Dr Eleftheriadou’s believes that in future the key to vitiligo management will be looking at the condition more holistically. Ensuring psychological interventions are used in conjunction with new and emerging treatments will help reduce the overall burden on patients and help to improve their quality of life.
