JAK Inhibitors and Lab Monitoring

With the rapid symptom control combined with the reassuring safety profile, JAK inhibitors such as abrocitinib (Cibinqo; Pfizer), baricitinib (Olumiant; Eli Lilly and Company), and upadacitinib (Rinvoq; AbbVie) can be considered as an important reliable systemic treatment option for adult patients with moderate to severe atopic dermatitis (AD) who are unresponsive to topical/skin-directed therapies, according to the authors of a recent study. For abrocitinib, baricitinib, and upadacinitib, close observation of treatment emergent adverse events (TEAEs) is required as well as serial complete blood cell count with differential for neutrophil and platelet monitoring, CPK levels, and lipid assessment.

“While needle-phobic patients may prefer an oral pill option, regular blood tests will be needed to monitor therapy,” noted coauthor, Andreas Wollenberg, MD, of Ludwig-Maximilian University in Munich, Germany. “Additionally, as a clinical measure of drug efficacy, it has been hypothesized that acne as a TEAE may be due to the pharmacological effect of JAK inhibition.”

Wollenberg highlighted those findings and more in a presentation on the efficacy, safety, and monitoring of JAK inhibitors at the Revolutionizing Atopic Dermatitis (RAD) Conference, held April 9 to 11, in Baltimore, Maryland.

He pointed out that there is no “by the numbers” good candidate for JAK inhibitors and added that JAK inhibitors could be used as first-line systemic therapy. Additionally, individual patient preferences and disease characteristics plays a large role in JAK inhibitor suitability. Patients with a preference for oral or flexible dosing might be interested in JAK inhibitors, he said.

Many patients are averse to using any needles. “Some people perceive injectables as inherently more dangerous, which is not necessarily true, but they have that perception,” said Jonathan I. Silverberg, MD, PhD, MPH, director, clinical research director, patch testing, associate professor, Department of Dermatology at The George Washington University School of Medicine and Health Sciences in Washington, DC, and conference chair of RAD. He added that by contrast, patients with a low tolerance for rare risk would not likely be good candidates for JAK inhibitors.

He prefers to look past AD classification to see how the individual patient’s life is affected over the course of a year. For example, a patient with frequent moderate flares might be a good candidate for an oral JAK inhibitor. Someone with severe seasonal flares might not be a candidate for a biologic, but the flexible dosing of a JAK inhibitor might enable the dermatologist to tailor the treatment regimen so that it better matches the patient’s needs without medicating 12 months of a year for a 3-month flare.

Wollenberg offered the following medical guidelines as a factor when considering starting a conversation with patients about JAK inhibitors. A history of malignancy, severe infection, a history of or high-risk for thrombosis or (main adverse coronary event) MACE, and severe renal or liver disease are all reasons to be very cautious when considering the use of a JAK inhibitor, he said. Elderly and pediatric patients would need a lower dose, and, he added, that he would proceed with extreme caution. As for medical indications that a patient would be a good candidate for JAK inhibitors, he cited very severe disease and complex comorbidities, as well as primary or secondary failure to a biologic or other systemic therapy.

What Patients Need to Know

Wollenberg added that the required laboratory monitoring recommended for patients receiving JAK inhibitors could also be a point of patient reluctance. “But the testing protocols were developed for the rheumatology applications of these drugs” and extensive monitoring is expected more frequently in that field. Based on clinical experience and available safety data for JAK inhibitors in AD treatment, some of those tests, such as a complete blood count, renal function, and comprehensive metabolic panel for liver enzymes, may be needed for each patient after the 12-week mark unless there is a dosage increase.

Disclosures:

Silverberg is a speaker, advisory board member, and/or investigator for: Abbvie, Afyx, Aobiome, Arena, Asana, BioMX, Bluefin, Bodewell, Boehringer-Ingelheim, Celgene, Dermavant, Dermira, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Kiniksa, Leo, Luna, Menlo, Novartis, Pfizer, RAPT, Regeneron and Sanofi-Genzyme. He has no patents, ownership, or financial gain from any atopic dermatitis drug.

Wollenbeg received grants, personal fees, or nonfinancial support from Abbvie, Aileens, Almirall, Beiersdorf, Bioderma, BMS, Chugai, Galapagos, Galderma, Hans Karrer, Janssen, Leo Pharma, Eli Lilly, L’Oreal, Maruho, MedImmune, Novartis, Pfizer, Pierre

Fabre, Regeneron, Santen and Sanofi-Aventis.

Reference:

Wollenberg A. Oral JAK inhibitor therapy in AD: Safety and laboratory monitoring. Presented at: Revolutionizing Atopic Dermatitis (RAD); April 9-11, 2022; Baltimore, MD.