Understanding Vitiligo | A Managed Healthcare Executive K-Cast

Vitiligo is an autoimmune disease that attacks melanocytes, or pigment cells, in the body, which causes white patches to appear on the skin. The exact prevalence of the disease is unknown, but it’s believed to be in the range of 0.5% to 2% of people worldwide. Most patients who present with this disease would like to be rid of it, but some patients just want to be accepted by others. Vitiligo can dramatically change one’s appearance.

Payer coverage decisions should follow the logic of response, said David Rosmarin of Tufts Medical Center in Boston. Calcineurin inhibitors should be the first-line treatment for facial vitiligo. If there’s no improvement after a few months, “then it’s reasonable to try (Opzelura),” and Opzelura should be the first choice for body involvement, for which calcineurin inhibitors are less effective, he said.

“There are people who don’t like to eat in restaurants because they feel like people are staring at them,” said David Rosmarin, M.D., vice chair of education and research in the Department of Dermatology at the Tuft Medical Center in Boston. “Certainly, children feel like they’re bullied and stared at, and they are asked, ‘What’s wrong with you?’ ”

Economic burden

Paying for clothes and cosmetics to hide vitiligo is a common economic burden, and treatment can also be costly. Phototherapy, one of the most common treatments, requires at least 70 treatments just to tell whether it’s working. Self-image problems can lead to depression or anxiety or worsen mental health problems that patients may already have, according to Rosmarin.

Vitiligo is a medical disease, not a cosmetic problem. Up to 25% of patients with vitiligo will also have autoimmune thyroid disease, such as Hashimoto’s disease or Graves’ disease. Other diseases that occur along with vitiligo are type 1 diabetes and pernicious anemia.

Treatment goals

Rosmarin grouped treatment goals into four categories. Some patients just want to know what their disease is, whereas others want to stop the pigmentation loss, and still more want to regain their natural coloring. The fourth goal is maintaining pigment after restoration.

Disease progression manifests in different ways. Most commonly, patients will have trichrome vitiligo, which consists of white patches, natural skin color, and an in-between color. Small white dots are also a sign of activity. Vitiligo may appear at the location of skin trauma, such as a tattoo or scratch, although that is less common.

A 12-week course of oral corticosteroids — often dexamethasone — is a common approach to halting progression of vitiligo. The treatment is usually well tolerated but may result in weight gain or trouble sleeping.

Phototherapy is the other most common treatment and may be given in combination with steroids. It can initiate repigmentation by “calming the immune system.” Phototherapy may be administered in a light box with narrowband ultraviolet B, and the preferred treatment is at least twice a week, according to Rosmarin. Small areas of depigmentation can be treated with an excimer laser. The third most common phototherapy combines a photosensitizer (psoralen) with ultraviolet A and is known as PUVA. It is not as well tolerated and is done less frequently.

Achieving repigmentation

To initiate repigmentation, patients are typically started on a combination of corticosteroids and topical calcineurin inhibitors. Careful management is critical because over long periods, steroids can cause thinning and lightening of the skin, atrophy, stretch marks and telangiectasias (enlarged skin blood vessels).

Calcineurin inhibitors are useful for sensitive places on the body, such as the eyelids, as use of corticosteroids in these areas may lead to cataracts or glaucoma. Corticosteroids are better suited for thicker skin, according to Rosmarin.

Recent results from large studies have shown that combining topical calcineurin inhibitors with phototherapy does not increase the risk of cancer, as was previously suspected, according to Rosmarin. Patients who cannot undergo phototherapy will start with topicals. If they don’t respond, doctors typically suggest phototherapy again as an add-on. “If yes and it works, then great,” Rosmarin said. “If not, then I may move on to JAK (Janus kinase) inhibitors.”

Opzelura, a major advance

In July 2022, Opzelura (ruxolitinib) cream became the first FDA-
approved medicine for repigmentation in vitiligo. Ruxolitinib is a JAK inhibitor, and this cream works particularly well on all body sites except the hands and feet, Rosmarin explained. One-third to 40% of patients who use Opzelura for a year find their vitiligo is a lot less noticeable or no longer noticeable. In adolescents, that number rises to over 50%. That makes Opzelura a first-line option for patients, along with corticosteroids, calcineurin inhibitors and phototherapy, he said.

Over-the-counter antioxidants and alternate therapies, such as ginkgo biloba and polypodium, may also be of some value. Micropigmentation, a form of tattooing to restore skin color, is an option, but Rosmarin warned that it should be done only by a very experienced professional and cannot be relied on for the dynamic range of natural skin tone.

Once pigmentation is restored, it is important to maintain it; for this, topical tacrolimus twice a week is recommended, according to Rosmarin. Phototherapy is also an option, he said. Further trials will reveal how well patients retain pigmentation following treatment with Opzelura.

The TRuE-V1 and TRuE-V2 studies were the basis for the FDA approval of Opzelura. Adult and adolescent patients with 3% to 10% of body space and some facial space affected by vitiligo were randomly assigned to Opzelura 1.5% twice daily for 24 weeks, followed by 28 weeks of Opzelura for all patients. At the end of the 24-week period, 30% of patients receiving Opzelura had a 75% or greater improvement in facial vitiligo vs 10% of those on placebo. “(This) is a meaningful outcome for patients,” Rosmarin said.

Facial repigmentation was chosen as an efficacy end point because repigmentation takes a long time and the face is faster to respond, he explained. The trunk and limbs are slower to respond, and the hands and feet are hardest to repigment.

At the one-year mark, 50% of patients had achieved a 75% or greater improvement in facial vitiligo, and half had achieved 50% or more repigmentation on their whole body. “This is (Opzelura) cream on its own, not in combination, where it may even work better and faster,” he said.

Opzelura was well tolerated, with 6% of patients getting acne, which was mostly mild, and 2% stopping treatment due to adverse events. In the subgroup analysis, race, ethnicity, age and disease duration made no significant difference in facial response.

Coverage issues

Rosmarin described Opzelura as a game changer. Patients who have failed on other medications can have success with this product. However, some payers still consider vitiligo to be a cosmetic disease. This leads them to deny coverage for calcineurin inhibitors, phototherapy and other treatments, although most cover corticosteroids because these are relatively inexpensive. Rosmarin expects Opzelura will lead to more favorable coverage decisions because of its FDA approval status.

Payer coverage decisions should follow the logic of response, he said. Calcineurin inhibitors should be the first-line treatment for facial vitiligo. If there’s no improvement after a few months, “then it’s reasonable to try (Opzelura),” and Opzelura should be the first choice for body involvement, for which calcineurin inhibitors are less effective, Rosmarin said.

Oral JAK inhibitors are useful in cases where there is rapid progression of vitiligo in multiple locations or for patients with a large surface area. “It’s also reasonable to try corticosteroids first on the body, as long as there’s no contraindication, but there has to be a reasonable window,” Rosmarin said.

Opzelura is indicated for patients with less than or equal to 10% of body area affected. However, the trials went as high as 20%, and at this level of application, Opzelura may be safer than oral treatments, he said. Not enough is known about why some patients don’t respond to Opzelura or the synergy between Opzelura and phototherapy.