Peter Wehrwein

Research has shown that patients with vitiligo are disproportionately affected by a variety of other autoimmune diseases, including rheumatoid arthritis, 

But less is known about the relationship between vitiligo and 

, a rare chronic condition that involves the buildup of scar tissue in the skin, joints and internal organs. Systemic sclerosis can result in pigment changes in the skin, including a loss of pigment that resembles vitiligo and a combination of loss and gain of pigment that causes a salt-and-pepper appearance.

A team of Israeli researchers led by Khalaf Kridin, M.D., Ph.D., used the database of Clalit Health Service, the largest HMO in Israel, to examine the relationship between vitiligo and systemic sclerosis. They identified close to 21,000 people in the database with vitiligo and a little over 100,000 who could serve as age-, sex- and ethnicity-matched control.

They found that the risk of developing systemic sclerosis was five times higher among the patients with vitiligo than the matched controls. The incidence rate of systemic sclerosis was 2.4 cases per 10,000 person-years among patients with vitiligo. Among the controls, it was 0.4 cases of 10,000 person-years.

In a smaller group of patients, Kridin and colleagues also looked at the risk of vitiligo among those a history of systemic sclerosis. After variety of statistical adjustments, they found that the risk of vitiligo was twice as high among people with systemic sclerosis.

Reasons for the association between vitiligo and systemic sclerosis were beyond the scope of this epidemiologic study, but Kridin and his colleagues shared some theories. Fibroblasts, the cells that product collagen and play a role in systemic sclerosis, affect pigmentation and therefore may play a causal role in vitiligo. Another possibility is that the autoimmune processes that cause vitiligo also play a role in causing systemic sclerosis.

This article originally appeared on Managed Healthcare Executive.

Articles

Israeli researchers find more than fivefold risk of developing systemic sclerosis among people with vitiligo.

Research Examines Link Between Vitiligo and Systemic Sclerosis

Multiple myeloma cannot be cured, but there are a growing number of late-line treatments for patients whose disease has not been controlled by other therapies.

The FDA announced that it had granted accelerated approval to Tecvayli (teclistamab), a bispecific antibody. It is the fourth, FDA-approve fifth-line treatment for multiple myeloma, a disease with an annual incidence of about 34,000.

Reuters reported that a spokesman for Johnson & Johnson said the company will price Tecvayli at $39,500 per month with the cost ranging between $355,000 and $395,000 for a nine to 10 month course.

The three other fifth-line therapies for multiple myeloma are 

, which the FDA approved in 2020, and two CAR-T therapies, Abecma (idecabtagene vicleucel) and Carvykti (ciltacabtagene autoleucel), which were approved earlier this year.

Bispecific antibodies act as a go-between, recognizing and attaching to cancer cells and joining them to the immune system’s T cells. That cancer cell-to-T cell attachment results in the T cells attacking cancer cells.

The FDA has approved three other bispecific antibodies as a cancer treatments: Blincyto (blinatumomab) for acute lymphoblastic leukemia, Rybrevant (amivantamab-vmjw) for nonsmall cell lung cancer and Kimmtrak (tebentafusp-tebn) for uveal melanoma.

Speaking at the AMCP Nexus 2022 meeting earlier this month, Kaelyn Boss, Pharm.D., a clinical consultant pharmacist at the UMass Chan Medical School, noted patients who receive Tecvayli may still need to be hospitalized because of the side effect of 

 (CRS), which is also a side effect of the CAR-T therapies. However, results from the clinical trial that led to the FDA’s approval decision show that instances of CRS from Tecvayli were mild.

Boss also noted that Tecvayli, as bispecific antibody, is an off-the-shelf therapy that doesn’t need to be customized manufactured for each patient as the CAR-T therapies do. As result, the Tecvayli may be more readily available, she said. It might also serve as a temporary “bridge” therapy to CAR-T therapy.

The clinical trial results, which were presented at the 

 meeting in June and published simultaneously by 

 showed an overall response rate of 63% (104 of the 165 patients for the trial) with 26.7% patients found to have no 

About 3 in 4 (72%) of the patients developed CRS but only case was deemed serious (grade 3), and no patient discontinued taking the drug because of CRS, the researchers reported in the journal article.

Infections were another side effect and 44.8% (74 patients) developed serious grade 3 or 4 infections and 12 patients died from COVID-19.

Because it is ‘off the shelf,’ Tecvayli may have advantages over the CAR-T therapies, which are custom made for each patient and involve harvesting the patient's T cells.

Late-Line Treatment for Multiple Myeloma Approved by FDA

One of the many questions hovering over Paxlovid (ritonavir-boosted nirmatrelvir is how much of a difference the antiviral treatment medication makes in people who have been vaccinated against COVID-19. The clinical trials that led to the FDA authorizing the medication that showed Paxlovid had a large effect on COVID-19 severity did not include people who were vaccinated.

The question hasn’t been fully answered but some evidence is coming in.

 about interim results from its EPIC-SR trial of Paxlovid that mentioned a sub-group analysis of 721 vaccinated adults with at least one risk factor for severe COVID-19. The press release said that Paxlovid led to a 57% reduction in hospitalization or death in that vaccinated group, although the difference didn’t meet the statistical standards for showing a real difference.

More recently, the research arm of Epic, the electronic health record company headquartered in Verona, Wisconsin, shared 

 showing large differences in hospitalizations and deaths between those treated with Paxlovid and those who hadn’t been treated with Paxlovid among people who had been vaccinated. The differences were larger among those 65 and older. But the Epic research also showed a difference in the 50-64 age group.

For example, there 27 hospitalizations (0.13%) and zero deaths among 20,407 peoplein that age who were treated with Paxlovid and who had been fully vaccinated and had had a booster. Among the 38,689 adults in the fully vaccinated, boosted group who were not treated with Paxlovid there were 143 hospitalizations (0.37%) and seven deaths (.02%). That works out to a hospitalization rate that is almost three times higher among those not treated with Paxlovid compared with those that were.

, vice president of informatics at Epic, noted that research findings from Israel had suggested that Paxlovid didn’t make a difference in the 50-64 age group. But that was a smaller study than the one conducted by her and her colleagues that might not have the statistical power to detect a difference. The size of Epic’s database, called Cosmos, is an advantage.

“On first look at these numbers, we not only saw a difference, but it was statistically significant, meaning that the confidence intervals didn't overlap, meaning that we could be very confident that there actually benefit to taking Paxlovid between age 50 and 64” Gerhart said.

Gerhart also looked at the hospitalization and mortality benefits of Paxlovid among those who were vaccinated but not boosted and those were vaccinated and double boosted. The results showing Paxlovid as protective against hospitalization and death were similar. The Epic researchers did not, though, break out Paxlovid results for people who are not vaccinated.

“We weren’t trying to say how much better protected you are being vaccinated and taking Paxlovid. We were trying to say, if you have already been vaccinated, is there still benefit to taking Paxlovid. And the answer is yes,” said Caleb Cox, an Epic Research lead.

Paxlovid has become the dominant form of treatment for COVID-19 in the United. According to a 

 by HHS, 5.2 million doses have been administered between the Dec. 7, 2021,and Oct. 9, 2022.

Findings by researchers at Epic, the electronic health record company, show that the benefits extend to people ages 50-64.

Hospitalization, Mortality Benefits Seen in Vaccinated Patients Who Took Paxlovid

The announcement of positive phase 3 results for the investigational Alzheimer’s disease drug comes against a backdrop of Aduhelm flaming out. Both drugs are predicated on the theory that Alzheimer’s is caused by beta-amyloid deposits.

After the failure of Aduhelm (aducanumab), Eisai and Biogen are back at it with another drug that is designed to treat Alzheimer’s disease by reducing beta amyloid deposits in the brain.

 last night announcing positive results for the drug, called lecanemab (development code: BAN2401) from a phase 3, placebo-controlled that included 1,795 participants with mild cognitive impairment due to Alzheimer’s disease or mild Alzheimer’s disease.

 in July 2022 that the FDA had agreed to put lecanemab on its accelerated approval pathway — the agency’s speedier approval process — and that an approval decision (the so-called PDUFA date) is scheduled for Jan. 6, 2023.

The announcement of the phase 3 trial results was treated as major news and was covered by the 

 as well as outlets that cover the biotech industry such as 

“In the first look at phase 3 data for lecanemab, Eisai and Biogen’s follow-up Alzheimer’s drug to the embattled Aduhelm launch, results show the drug passed with flying colors on a test looking at memory, problem solving and other dementia metrics” was the lede on the 

’s story: “The positive result is welcome news for the millions of people living with Alzheimer’s and a big win for Eisai and Biogen, giving the companies a potential blockbuster product…”

According to last night’s press release, lecanemab met the primary endpoint of reducing cognitive and functional declined as measured by a test the Clinical Dementia Rating-Sum of Boxes (CDR-SB). More specifically, the treatment reduced decline by 27% compared to those in the placebo group, the press release said.

As with Aduhelm, brain swelling and small bleeds are side effects of lecanemab. The press release says that 21.3% of the people in the lecanemab group had swelling or bleeds compared with 9.3% in the placebo. However, the proportion of patients who had symptoms from swelling and bleeds was far less (2.3% in the lecanemab group had symptoms from brain swelling and 0.7% had symptoms from brain bleeds).

The press release said Eisai researchers will present the results from the phase 3 trial, which is called Clarity AD, at the 

 Congress meeting in San Francisco on November 29, 2022, and also publish them in a peer-reviewed journal (the journal was not named in the press release).

Lecanemab and Aduhelm are both designed to reduce beta-amyloid plaques in the brain and, as such, are predicated on theory that those plaques have a causative role in Alzheimer’s disease. The press release about lecanemab quotes Haruo Naito, the CEO of Eisai, as saying the positive results for lecanemab “prove the amyloid hypothesis.”

Eisai and Biogen teamed up on Aduhelm, but the problematic drug was strongly associated with Biogen. Yesterday’s press release says that Eisai will be leading the development and regulatory submissions process for lecanemab.

Eisai’s ($ESLAY) stock price shot up by more than 60% today and was trading at $63.61 this afternoon. Biogen’s ($BIIB) stock price was up by almost 40% and was trading at $274.70 this afternoon.

The positive news and spin about lecanemab yesterday and today stand in stark contrast to the controversy that engulfed Aduhelm.

When the FDA approved the Aduhelm on June 7, 2021, three members of the outside advisory committee that had recommended that it not be approved resigned in protest. One of the resigning members called the FDA’s OK of Aduhelm “probably the worst drug approval decision in recent U.S. history.” The clinical trial results for Aduhelm were ambiguous with one trial showing a positive result (as measured by scores on the CDR-SB) and the other, not. Press reports said the agency’s approval of Aduhelm was one of the reasons that interim commissioner, Janet Woodcock, did not get the job on a permanent basis.

The pricing of Aduhelm also created headwinds for the drug and Biogen. It was originally priced so a year of treatment would cost $56,000. The Alzheimer’s Association and other groups objected. Biogen later slashed the price in half.

Then in April 2022, CMS announced that it would restrict coverage of Aduhlem to people enrolled in clinical trials. In June, Biogen pulled the plug on what was to be a large real-world evidence of Aduhelm called ICARE-AD. The statement on the clinicaltrials.gov website says that “as a result of the national policy for coverage, it is expected there will be limited aducanumab-avwa prescription and usage in routine clinical practice making the study not feasible for enrollment.”

Lecanemab Hopes to Succeed Where Aduhelm Failed

When the FDA approved Opzelura as a treatment for nonsegmental vitiligo in July, the agency heralded the whitish cream as the “first FDA-approved pharmacologic treatment to address regimentation in vitiligo patients.” Opzelura had been previously approved as treatment for atopic dermatitis.

Opzelura contains ruxolitinib, an inhibitor of Janus-activated kinases (JAKs) and, more specifically, the JAK1 and JAK2 (there is also JAK3 and tyrosine kinase 2 in the JAK family of enzymes). The Janus kinases are believed to play a key role in orchestrating the complicated signaling pathways for cytokines and growth factors.

Ruxolitinib may have some company. A number of other JAK inhibitors are under investigation as treatments for vitiligo, an autoimmune disordered characterized by whitish areas of skin that are the result of a loss of melanocytes. Melanocytes produce melanin, a dark skin pigment.

 about advances in vitiligo treatment listed five JAK inhibitors as candidates for vitiligo treatment. Even so, the FDA-approved label for Opzelura has a pointed reminder that the relationship between the JAKs and their inhibition and vitiligo isn’t entirely understood. The label says that the “relevance of inhibition of specific JAK enzymes to therapeutic effectiveness is not currently known.”

Here are six JAK inhibitors discussed in the 

 is a JAK1 and JAK3 that is the active ingredient in Xeljanz. The review article says that five- to 10-milligram (mg) doses once or twice a day have shown some effectiveness as treatment for vitiligo. But review also mentions side effects from the oral version, including infections, cancer and cytopenia, and it suggests that a topical version may therefore be preferred. The review discusses positive results from a small (11 patients) trial of a tofacitinib cream.

 is a JAK1 and JAK2 inhibitor that is the active ingredient in Olumiant. The review article says that there has been a case report of repigmentation in vitiligo in patients taking four-mg doses of baricitinib as a treatment for rheumatoid arthritis. According to the review, there is a 

 underway evaluating baricitinib in combination with phototherapy as a treatment for vitiligo.

 also known provisionally as ATI-50002, is a JAK1 and JAK3 inhibitor. It is also under investigation as a treatment for alopecia areata,

, also known provisionally as PF-06651600, is a JAK3 and tyrosine kinase inhibitor. It is being evaluated in a clinical trial as a treatment for vitiligo along with another experimental agent, 

, a JAK1 and tyrosine kinase inhibitor that has the provisional code name of PF-0670084.

Pfizer put out a press release earlier this month to announce that the FDA had accepted its application for ritlecitinib as a treatment for alopecia areata and that the FDA is expected to make an approval decision during the second quarter of next year.

In June, Pfizer issued a press release trumpeting the phase 2 trial results for oral brepocitinib as a treatment for psoriatic arthritis, plaque psoriasis, ulcerative colitis, alopecia areata and hidradenitis suppurativa.

 is a spleen tyrosine kinase inhibitor as a well as a JAK inhibitor. According to the federal government’s clinical trial database, clinicaltrials.gov, 

 as a vitiligo treatment was completed in 2020 but no results are posted on the clinicaltrials.gov. Researchers are also evaluating cerdulatinib as a cancer drug and, more specifically, as an agent might be used to treat patients with non-Hodgkin lymphoma and peripheral T-cell lymphoma.

A recent review article lists six other JAK inhibitors that might be used as treatments for vitiligo in addition to ruxolitinib, the active ingredient in recently approved Opzelura.

Other JAK Inhibitor Options for Treating Vitiligo

The history of medications to help people lose weight does not inspire a lot of confidence. Amphetamines, the fen-phen (fenfluramine-phentermine), sibutramine (sold under the brand name 

) — they helped people lose weight. But they also had dangerous, sometimes fatal, side effects.

But in June 2021, FDA approved the repurposing of a diabetes drug, semaglutide, as a weight-loss drug that Novo Nordisk is selling under the brand-name Wegovy.

And at the 2022 Pharmacy Benefit Management Institute (PBMI) Annual National Conference today in Orlando, Florida, a pharmacy benefits management (PBM) executive and Novo Nordisk executive said the good safety track record of semaglutide as a diabetes drug and the class of drugs to which it belongs, called glucagon-like peptide 1 (GLP-1) agonists, should be reassuring.

“Now that we are in the millions of patients on the product, it gives me confidence that it is not only effective (against diabetes) but also safe,” said 

, RPh, chief operating officer for WellDyne.

, Pharm.D., a medical account associate director for Novo Nordisk, said the GLP-1 agonists have been used to treat diabetes for over a decade. “If there were safety concerns, we would have seen signals by now.” He added that the cardiovascular outcomes for the GLP-1 agonists when they have been used as diabetes medications have shown benefit, not harm, when it comes to cardiovascular disease.

Wegovy’s average wholesale price is $1,300 per month. It is unclear now whether payers will reap immediate savings from people losing weight and avoiding comorbidities or reducing the use of medications for obesity-related conditions such as a hypertension.

Skomo and Flugge both spoke about the growing proportion of people in the U.S. who are overweight or have obesity. Skomo, referencing data from the CDC, said the proportion of Americans who are obese has increased by 40% over the past 20 years and the proportion that is severely obese(a body-mass index [BMI] of 40 or more) has doubled.

Obesity needs to be a reframed as a progressive chronic disease that needs to be managed rather than a failure of self-control to exercise and eat a healthful diet, Skomo told the PBMI conference attendees.

“It is a chronic disease that they (people with obesity) struggle with and we have to think about it in that way,” Skomo said.

Skomo showed survey results showing that employers are interested in addressing obesity but look to wellness programs as the way to do so. He argued that PBMs can play a role now that Wegovy is on the marketand a wave of other diabetes drugs are also expected to be weight-loss indications from the FDA and be sold for that purpose.

PBMs should be putting these new weight-loss drugs on their formularies as preferred brands, Skomo said, and also encourage coverage by making them an opt-out choice for payers rather than opt-in. He also said PBMs should impose prior authorization rules to assuage payers concerns about misuse and ballooning costs. Skomo says uses the Wegovy’s FDA-approved label to set its prior authorization rules. The label says the drug is indicated for use in people who are obese (a BMI of 30 more ) or who are overweight a BMI of 27 or more who also have a health condition related to being heavy.

The harm caused by weight-loss drugs have overwhelmed any benefit they may have. The repurposed diabetes drugs like Wegovy (semaglutide) have a strong safety profile.