Dermatology

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The symposium and publication of this article were sponsored by Incyte Biosciences International Sàrl

Vitiligo, Beyond White Patches

Open Meeting Summary

Intended for Healthcare Professionals Only

Q:

YES

NO

Do you consider vitiligo to be a serious medical disease?

INTRODUCTION

Vitiligo is a chronic autoimmune disease caused by a deregulation of the immune response that results in epidermal melanocyte destruction.1

The characteristic depigmented lesions are often associated with psychological distress for patients, resulting in negative effects on mental health and QoL, with vitiligo being associated with social isolation, stigma, depression, and anxiety.2

  • With a variable and unpredictable disease course, vitiligo consists of stable periods, spontaneous repigmentation, and new patches or flares.
  • Vitiligo is a serious medical condition and therefore should be treated as a priority. 

How the Underestimated Vitiligo Burden Impacts Optimal 
Care Albert Wolkerstorfer

Wolkerstorfer opened the session by considering the burden of vitiligo and what it is to live with vitiligo, including its impact on appearance, unpredictable flare-ups, itching, and association with autoimmune disorders.

He said that patients are desperate because of their vitiligo, 
explaining that even those patients who look self-confident, self-assured, beautiful, and strong, all had difficult times in life,” with regards to their vitiligo, stating that “appearance does matter” to those with vitiligo.3 

Living with the Burden of Vitiligo, Including Psychological Comorbidities

The global VALIANT study indicated that the extent of vitiligo matters. The more extensive the affected BSA, the higher the rate of moderate-to-severe depressive symptoms, highlighting the urgency to treat as early as possible.5

X5

more likely to 
have depression.6

1

Living With the Burden of Vitiligo, Including Psychological Comorbidities 

2

Parallels Between Vitiligo and Other Skin Disorders

Access to Optimal Care and Hurdles in Vitiligo Care

Wolkerstorfer stated that “the patient journey starts long before the diagnosis,” and there are many issues along the patient journey which decrease access to optimal vitiligo care (Figure 1).20 

Many receive no treatment.8 Insufficient information about treatment options, and a lack of shared decision-making.15 

Disease management 1:  Treatment initiation

Public knowledge,15 and understanding of the condition in general.20 

Symptom recognition / pre-diagnosis 

Disease management 1:  Treatment initiation

Diagnosis

Delay in diagnosis, misdiagnosis, HCPs downplaying the disease as a cosmetic issue, that ‘vitiligo is untreatable.’15 
No adequate information.21 

A European White Paper, along with the speakers at the symposium, highlighted the official classification of vitiligo as a chronic autoimmune disease.23,24

Changing
the Trajectory of Vitiligo in Europe 

Wolkerstorfer concluded that the burden of vitiligo is significant. Though there are many parallels to other chronic skin disorders, some specific items make vitiligo very resistant and difficult to treat. Access to optimal care is sometimes very difficult, and there are some hurdles still to tackle.

As an Autoimmune Disease, Vitiligo Warrants Both Early and Long-Term Considerations Curdin Conrad

  • Considering the treatment of chronic inflammatory diseases, Conrad highlighted the importance of finding treatment options that balance improving skin lesions while minimising side effects. He said this involved considering factors such as efficacy, benefits, risks, side effects, and inconveniences.25 
  • The session emphasised the need to understand the pathogenesis of the deregulation of the immune system in order to understand the disease and then identify treatment opportunities.  
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Non-segmental vitiligo is a chronic T helper (Th)-1 autoimmune disease.26,27 Conrad drew comparison to other immune diseases such as psoriasis, which is a Th-17 driven disease, and lupus which is driven by Type I-interferon; alopecia areata and vitiligo are driven by Th-1 via interferon-γ, which was demonstrated by the overexpression seen in gene expression profiles. 

Disease course and the memory of vitiligo and long-term options

  • The challenge with current treatment options is that after successful therapy, such as phototherapy, many patients relapse within 12 months with recurrent depigmentation that typically occurs in the same lesions. This Conrad highlighted, indicated the “development of a disease memory within the skin.” He proposed that a longer disease duration may be a risk factor for (earlier) relapse.
  • Therefore, “early intervention, we have a higher chance to tackle that problem,” and have a higher chance of the patient going into remission and avoiding a relapse. Conrad said that this could potentially “reverse disease memory or prevent its establishment.” 

The role of tissue resident memory T cells in the skin

Objectives for Long-term Vitiligo Treatment

  • The need to halt depigmentation, slow the disease progression, prevent relapses, and have time to induce re-pigmentation can take 6 months up to 2 years or more.20 Conrad concluded that the aim for early intervention, to enable disease modification by preventing or reversing the skin population of TRM and preventing or reversing epigenetic changes is still yet to be seen.
  • However, there is a need to tackle the burden of disease through early intervention and as early as possible so that we have treatment options available, and that there is a need for long-term management.
  • Considering the pathogenesis of vitiligo, the session identified potential treatment targets to block early depigmentation by targeting interferon-γ and to prevent relapses by blocking IL-15 to prevent TRM cell activation or maintenance, which can be achieved through JAK1 inhibition (Figure 2).2,30,42-50 Conrad summarised that it makes sense to inhibit Th-1 through JAK1 inhibition as an option to achieve vitiligo remission and long-term control. 

Figure 2: The vitiligo pathogenesis and objectives in vitiligo treatment.2,30,42-50  

Figure adapted from Qi F et al.46 CC-BY-4.0 

Which JAK member(s) are inhibited by ruxolitinib cream?

Q:

JAK 1

JAK 2

JAK 3

TY2K

SUBMIT

How Ruxolitinib Cream Fits in Shared Decision-Making Strategies for Effective Vitiligo Management Markus Böhm

In the final presentation, Böhm highlighted the importance of shared decision-making strategies in treating patients with nonsegmental vitiligo.  

1

Shared Decision-Making Strategies 

Shared decision-making is an important tool in long-term management of chronic conditions such as vitiligo.51

2

Targeted Therapy for Vitiligo with Ruxolitinib Cream  

To support HCPs' understanding of treatment options, Böhm presented data from the first vitiligo-specific immunomodulatory therapy, a selective JAK1 and JAK2 inhibitor, ruxolitinib topical cream

Shared decision-making is an important tool in long-term management of chronic conditions such as vitiligo.51  

Put simply, Böhm said shared decision-making is the “provision of information to the patient, and also to listen to the patient.” This includes considering patient expectations, providing clinically relevant information, considering the nature of the disease, diagnosis and consequences, and treatment options, including what areas are difficult to treat, expectations of available therapies, and that some areas may not respond well.51


Another point identified by Böhm is that when explaining clinical data to patients, is to explain that it takes time. He said that unlike psoriasis or atopic dermatitis, with endpoints within 16 weeks or 24 weeks, it takes from 24 up to 52 weeks for vitiligo. Böhm indicated that if patients are not responding immediately, they should be persistent with the treatment.

  • Böhm concluded that shared decision-making is a important tool for the successful therapeutic management of patients with vitiligo, particularly when considering newly approved therapies.
  • Long-term treatment is usually needed in vitiligo, making shared decision-making an even more important tool considering the burden of using treatment against the need to get improved responses when treated for longer. 

CONCLUSION

  • The burden of vitiligo and the challenges of accessing optimal care highlight the importance of both early and long-term management.
  • Vitiligo is a chronic autoimmune disease that is characterised by melanocyte loss, which results in depigmented skin, driven by the JAK-STAT pathway.
  • Dermatologists have the opportunity to lead the way in the successful development of therapeutic management, with shared decision-making as an important cornerstone.
  • Ruxolitinib cream is a JAK inhibitor that facilitates quality repigmentation by inhibiting the JAK-STAT pathway.
  • Patients receiving any treatment for vitiligo should be advised that repigmentation is gradual due to melanocyte regeneration, and requires persistence of 6–12 months+ for satisfactory re-pigmentation.

References

EU/RUXO/NP/24/0009

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