Jared Kaltwasser

Janus kinase (JAK) inhibitors appear to be effective treatments for patients with atopic dermatitis (AD), according to a new systematic review of 14 randomized controlled trials.

The trials assessed 3 different oral JAK inhibitors, abrocitinib (Cibinqo), baricitinib (Olumiant), and upadacitinib (Rinvoq). The review was 

Corresponding author Kevin P. Lee, of the University of Texas at Houston, and colleagues, wrote that many patients with AD are successfully treated with topical therapies like corticosteroids, calcineurin inhibitors, and phosphodiesterase inhibitors. 

Non-responders to topical therapy are sometimes treated with phototherapy, systemic therapies like methotrexate and cyclosporine, or other immunosuppressive agents.

However, Lee and colleagues noted many patients still do not achieve clear or almost clear skin with existing treatments. Thus, they said more treatment options are needed.

One potential option is JAK inhibitors, which mounting evidence suggests can be effective in treating moderate-to-severe AD. 

While multiple studies are currently underway to evaluate JAK inhibitors for AD, Lee and colleagues decided to see what the existing literature says about their potential.

The investigators searched scientific databases for randomized controlled trials of JAK inhibitors for treating AD. 

The team then extracted the data from those studies to perform a meta-analysis that analyzed 4 outcomes: Eczema Area Severity Index (EASI)-75 response (responses greater than 75% from baseline), EASI percent change, percentage of patients judged clear or almost clear via Investigator Global Assessment (IGA), and 4-point or greater improvement in pruritus numerical rating scale (NRS) score.

Altogether, the authors found 14 trials, including 7,051 total subjects. The trials assessed abrocitinib (100 and 200 mg), baricitinib (1, 2, and 4 mg), or upadacitinib (15 and 30 mg) for the treatment of moderate-to-severe AD.

The results were promising. All 3 therapies led to improvement in all 4 outcome metrics compared to placebo, the authors found. However, one therapy stood out. The investigators said upadacitinib at 30 mg led to the best results in all 4 outcomes among all of the drugs and dosages.

“[O]ur study demonstrated that JAK inhibitors are an effective treatment for AD,” they wrote. “We found that upadacitinib, particularly at 30 mg, was significantly more efficacious than both abrocitinib and baricitinib in every outcome analyzed.”

In terms of safety, the authors said their meta-analysis showed patients taking JAK inhibitors had a higher percentage of herpes zoster infection than the placebo-controlled group. In addition, they noted that the immunomodulatory properties of JAK inhibitors have raised concerns about an increased risk of malignancy. 

The team added that 8 patients taking upadacitinib and 2 patients receiving placebo were reported to have malignancies. However, Lee and colleagues said most of the cancers were not believed to be related to the drug, and suggested longer-term safety data would be required to fully understand the risk of malignancy for patients taking these drugs.

In conclusion, the investigators believed JAK inhibitors appeared to show promise as a treatment for AD, but they said more clinical trials, including trials directly comparing JAK inhibitors, will be needed to confirm the results.

Articles

Oral doses of 3 Janus kinase inhibitors show the therapies out-performed placebo in all outcomes measured in patients with moderate-to-severe AD.

Systematic Review Suggests Oral JAK Inhibitors Effective in AD

Half of patients with rosacea have ocular involvement, but a significant number of cases go undiagnosed due to a lack of symptom specificity, according to a new analysis.

The report was a rare large-scale study of ocular rosacea that offered insights into how physicians could better identify and treat patients with rosacea who may have eye involvement.

Corresponding author Markus Reinholz, MD, PhD, of the University Hospital of Munich, and colleagues, noted that rosacea is most identifiable as an inflammatory disease affecting the facial skin, but it can also extend to the eyes.

However, the author said the ocular manifestations of the disease have received relatively little attention until recently. Yet it remains a multidisciplinary challenge.

“Ophthalmic rosacea can affect the eyelids (blepharitis, chalazion, and meibomianitis), the conjunctiva (conjunctivitis and keratoconjunctivitis sicca), the iris (iritis and iridocyclitis), and the cornea (corneal thinning, ulceration, and superficial keratitis),” they wrote.

Patients with the condition often report symptoms such as burning, tearing up, and photophobia. The condition is generally classified into one of 3 categories, based on severity.

Though much is known about the disease, at least 2 major questions remain: first, how exactly does the disease come about and second, how common are ocular manifestations among patients with rosacea.

In an effort to answer the latter question, the investigators developed a detailed online questionnaire, which was given to 777 patients with rosacea.

The survey asked patients questions about ocular and skin symptoms, type 1 hypersensitivities, Demodex testing results, and their previous experiences with healthcare professionals.

The surveys showed that a slight majority (399 of 777) experienced ocular symptoms. The most common were styes and chalazia (309 of 399), itching (187 of 399), and red eyes (179 of 399).

About half of the patients (393) in the study had type 1 hypersensitivity, and more than half of those (225) said they suffered from ocular symptoms.

The investigators said it is important for physicians to question patients with rosacea about ocular symptoms. If symptoms are present, it is beneficial to refer patients to an ophthalmologist for a full examination, since eye symptoms are often unspecific and may or may not be related to rosacea.

In the study cohort, 309 patients had previously consulted an opthalmologist, and about half (149) were confirmed to have ocular rosacea.

If patients do have ocular rosacea, Reinholz and colleagues said, dryness of eyes can be helped by intense pulsed light (IPL) therapy and the use of artificial tears with omega-3 fatty acids, according to previous studies.

The investigators also discussed the topic of Demodex infection, since it has been discussed as a probable trigger of ocular rosacea. In the current study, no statistically significant association was identified between Demodex prevalence and ocular rosacea manifestation.

That may be because Demodex-induced symptoms could be dose-dependent or dependent on individual immunologic mechanisms, they said. In the study, 45 patients were Demodex-positive, and just half (21) had ocular symptoms. 

The authors said their study’s strength is its large size and broad scope of symptoms, but they said more work will be needed to better understand the mechanisms that cause ocular rosacea to develop, as well as the role of potential risk factors.

“Here, immunological studies will be key to elucidate the exact triggers of this chronic inflammatory disease,” they said.

"Clinical clues to identify patients with ocular rosacea – a Germany-wide epidemiologic analysis,"

About half of a cohort of nearly 800 patients said they experience ocular symptoms.

Ocular Symptoms Common in Rosacea, But Often Undiagnosed

Patients with epidermolysis bullosa (EB) experience a significant impact on their quality of life, but a new report is calling attention to the ways the disease can impact members of the patients’ families, as well as the healthcare professionals treating them.

Epidermolysis bullosa is a rare form of genodermatosis that causes mucocutaneous fragility, explained the review’s authors, including corresponding author Antoinette V. Chateau, BSC, MBCHB, of the Grey’s Hospital, in South Africa.

The global prevalence is just 19.57 cases per 1 million live births. The disease has 4 groups and 30 subtypes, and patient prognosis varies subtype, they said.

“The clinical presentation and complications vary from very limited vesicles or nail involvement to extensive disease resulting in skeletal deformity, systemic manifestations, and malignancy,” Chateau and colleagues wrote.

Though the disease can have a dramatic impact on the lives of patients, most of the research into the condition has focused on diagnostics and therapies. Less has been written about how the burden of the disease affects healthcare providers or other family members, such as parents and siblings.

Chateau and colleagues decided to search for peer reviewed qualitative, quantitative, or mixed-methods studies and case reports that included data on the psychological impacts of EB on parents, caregivers, or siblings of children with EB or on healthcare professionals.

After exclusions, they found a total of 27 relevant studies. A number of themes emerged from the literature, the authors said.

“Having a child with a potentially life-limiting disease, depending on the subtype, can be devastating for the parents and the family as a whole,” Chateau and colleagues wrote. Thus, they said, strong family bonds and support systems are critical.

The disease can also have a significant impact on the relationships of the parents and can affect parents’ decisions on whether to have more children. Chateau and colleagues said families should be sure to prioritize less-stressful family time, such as vacations and recreation, in order to prevent family breakdown.

The team also noted that the data show women typically take on a greater burden when it comes to caring for patients; fathers ought to be intentional about helping to care for children, they wrote.

In the studies, parents said rapid referrals to specialists are important, but they also noted that the disease brings with it significant burdens, including the cost of care and difficulties with understanding how best to care for their children.

Data on the impact of EB on patient siblings were rare, but Chateau and colleagues said the disease can lead to both practical and emotional implications for children. Siblings sometimes feel guilt that they did not get the disease, but at other times they can be overtaken by fear for their sibling or resentment about the way the sibling’s condition has burdened their family.

Siblings were also affected if parents did not adequately prepare them for what they might experience when visiting their sibling in the hospital.

The genetic implications of the condition also create difficult decisions for parents about what to tell their other children, and when.

Finally, the authors discussed the disease’s effects on healthcare professionals treating patients with EB. They said strong doctor-patient relationships are key, but that physicians should also adopt a comprehensive, multi-disciplinary approach to ensure families are empowered and well cared-for.

“It is vital to be cognizant of these dynamics and be holistic and comprehensive in addressing the family’s challenges, difficulties, and needs,” the team wrote.

Physicians can expect significant challenges, including a lack of available EB specialists, and ethical questions such as whether to offer life-extending therapy and/or life-shortening pain relief.

“To cope, [healthcare professionals] require self-care strategies, debriefing, and being part of support groups,” Chateau and colleagues wrote. “They should not work in isolation but rather in a multidisciplinary team, having access to psychological support, and reducing compassion fatigue and burnout.”

The investigators closed by calling for more research, both to address gaps in knowledge about the burden of EB, and to consider the cultural contexts of patients and families.

"The impact of epidermolysis bullosa on the family and healthcare practitioners: a scoping review,"

Most research into the rare condition is focused on therapies and diagnostics, but investigators say it is important to better understand the disease’s impact on those around the patient.
 


Epidermolysis Bullosa Causes Significant Burden for Patients, Families, and HCPs

Treatment-emergent herpes simplex infection is common among patients with atopic dermatitis (AD) who are treated with baricitinib (Olumiant), but cases of eczema herpeticum and herpes zoster are not common, according to new research.

Even when patients became infected, however, cases tended to be mild or moderate and usually did not lead to discontinuation of the medication.

Previous research has indicated that patients with AD are at a higher risk of bacterial and viral infections, in part because they have reduced levels of interferon-γ and its receptor and express receptor variants, explained corresponding author Andreas Wollenberg, MD, of Ludwig Maximillian University of Munich, and colleagues.

The reduction is particularly notable in patients with a history of eczema herpeticum, the authors noted. Since interferons are mediated through the Janus kinase 1 and 2 (JAK1 and JAK2) pathways, and baricitinib is a JAK1/JAK2 inhibitor, Wollenberg and colleagues said cases of eczema herpeticum are of particular interest in patients with AD who receive baricitinib.

Baricitinib has been associated with increased rates of treatment-emergent herpes zoster infection in patients being treated for rheumatoid arthritis, the investigators noted, but the primary evidence available for AD is limited.

The authors said there remains a need for a better understanding of barictinib’s disease-specific safety profile and characteristics in patients with AD.

Wollenberg and colleagues reviewed 6 double-blinded, placebo-controlled trials, and 2 long-term extension studies of baricitinib in patients with AD in order to determine how commonly patients experienced treatment-emergent herpes simplex infections, including eczema herpeticum and herpes zoster. All of the patients in the studies were adults, and all received at least 1 dose of the drug.

In all, 2,351 patients representing 2,247 person-years were included in the analysis. Herpes simplex infections were reported in 8.9% of patients, but 93.3% of those cases were characterized as mild or moderate.

Patients permanently discontinued the therapy in just 2.2% of cases. Treatment-emergent eczema herpeticum, meanwhile, was reported in just 1.7% of patients. Again, most cases (79.1%) were considered mild or moderate, and three-quarters of cases (74.2%) were one-time events.

That rate was lower than in previous reports, but the authors noted a significant caveat: the clinical trial protocols called for patients with a history of eczema herpeticum to be excluded from the trial, “which may explain the lower frequency,” the authors said.

Finally, 2.1% of patients experienced treatment-emergent herpes zoster infections, but there was no dose-dependent relationship. The investigators noted treatment-emergent herpes zoster infections were less frequent in patients who received 4-mg doses of baricitinib than in patients receiving a lower dose.

The frequency of infections did not increase with prolonged exposure to the drug, and no serious adverse events of herpes zoster were reported.

Overall, the data as a whole suggested patients with AD who wee treated with baricitinib faced an increased risk of herpes simplex infections, but those cases are generally uncomplicated.

“These events were mostly mild-to-moderate, presented as localized oral/perioral herpes simplex, and rarely led to discontinuation,” the team concluded.

"An integrated analysis of herpes virus infections from eight randomised clinical studies of baricitinib in adults with moderate to severe atopic dermatitis,"

The new analysis suggests the infections rarely leads to discontinuation in patients with atopic dermatitis.