Combined Therapy With Narrow-Band Ultraviolet B Phototherapy and Apremilast for the Treatment of Vitiligo
Status:
Completed
Trial end date:
2019-08-05
Target enrollment:
Participant gender:
Summary
Vitiligo is a common acquired disorder of pigmentation affecting 0.5% to 1% of the world
population. Sharply demarcated patches of depigmentation, which can affect all ethnicities,
and can lead to cosmetic disfiguration and psychosocial distress, characterize the disease.
The etiology of vitiligo remains unknown. Various mechanisms have been proposed, such as
autoimmunity, self-destruction, biochemical, genetic, neural, oxidative stress, and an
imbalance of epidermal cytokines leading to inflammation and selective loss of epidermal
melanocytes. Currently, the most popular theory is autoimmunity. Previous studies noted that
around 25-30% of patients have at least one other autoimmune disease, such as autoimmune
thyroid disease, Addison's disease, pernicious anemia, and alopecia areata. Currently, NB-UVB
phototherapy is the most widely used therapeutic option for vitiligo affecting more than
10-20% of the skin surface, as it is generally considered to be a safe initial treatment.
Potential side effects include phototoxic reaction, thickening of the skin and
koebnerization. NB-UVB is a band of UV radiation with a wavelength of 311-313 nm. UVB induces
mitogenesis and migration in melanocytes mediated by several factors such as IL-1, TNF alpha,
and leukotriene C4. UV radiation produces increased number and activity of melanocytes,
increased melanin density, elongation and branching of dendrites, with increased transfer of
more heavily melanized melanosomes to keratinocytes, seen clinically as increased
pigmentation. Apremilast is an oral small molecule phosphodiesterase-4 (PDE4) inhibitor that
has been shown to regulate inflammatory mediators. Apremilast enters cells by passive
diffusion and, once intracellular, binds PDE4. PDE-4, the dominant phosphodiesterase
expressed in immune cells, degrades cyclic AMP (cAMP) into AMP. PDE4 inhibition thereby
elevates intracellular cAMP, which can down-regulate the inflammatory responses such as
TNF-α, IFN-γ, interleukins (IL) 2, 12 and 23 through mechanisms such as partially inhibiting
expression of inflammatory cytokines and increasing expression of anti-inflammatory mediators
such as IL2 and IL10. The hypothesis is that apremilast will shut down the inflammatory
insult in vitiligo and NB-UVB phototherapy will then be able to regenerate melanocytes and
their activity. By examination of skin biopsies taken pre- and post-therapy, the study team
aims to assess changes in immune and cellular markers in affected skin.