Baricitinib effective in cutaneous manifestations of dermatomyositis

Dermatomyositis(DM) is a rare autoimmune collagen vascular disease with cutaneous and systemicinvolvement significantly impairing quality of life. Induction of type Iinterferon (IFN) and its IFN-stimulated genes (ISGs) was discovered in patients'blood, muscle and skin. Current treatment options are only partially effectivein DM-associated panniculitis. Inhibiting the activation of Janus kinase(JAK)-transmitting signals of the type I IFN receptor is a valuable therapeuticoption. Recently an article showing efficacy of JAK inhibitor baricitinib in cutaneousmanifestations in juvenile DM was published in the British Journal ofDermatology.

Theprominence of type I IFN signature in DM was the basis for trial of barcitinibin 3 patients of DM. Patient1 had experienced a recurrent disease course for 25 years and was on partialremission with low-dose prednisolone (5 mg per day),methotrexate, hydroxychloroquine and adalimumab. She presentedwith a new disease flare with violaceous erythema prone to the face, collar, neckand periungual area, but normal muscle enzymes. The therapy with methotrexateand adalimumab was terminated due to an increase in liver enzymes. Thereafter,tofacitinib was started but was not well tolerated because of lactose intolerancein the patient. Therefore, the therapy was changed to baricitinib 4 mg daily.The neck, facial and periungual erythema completely regressed within 5 monthsof treatment

Patient2 had experienced anti-NXP2 antibody-positive DM with severe muscle weakness,facial and abdominal erythema and an erythematous, painful and ulceratedsclerosing plaque in the lower back that was histologically confirmed aspanniculitis. While the initial DM skin rash and muscle weakness resolved undertherapy with high-dose prednisolone, azathioprine and monthly infusions ofIVIG, the ulcerative panniculitis showed no long-term remission. Subsequently,therapy with baricitinib 4 mg daily was initiated. Concomitant medication withprednisolone 5 mg and one cycle of IVIG per month was continued. Afterinitiation of baricitinib treatment, the panniculitis improved, and resolvedwith residual scarring after 4 months. IVIG was stopped and remission wasmaintained by baricitinib treatment. Interruption of therapy for 1 month, 6months later induced an immediate flare of ulcerative panniculitis that waseffectively controlled by reinitiating baricitinib alone.

Patient3 was diagnosed with anti-MDA5 antibody-positive DM with prominent and severeskin involvement. No interstitial lung or significant muscle involvement was detected.Initial treatment consisted of prednisolone, hydroxychloroquine 200 mg andmethotrexate. Methotrexate was discontinued due to leucopenia and an abscess inthe axilla. Thereafter, treatment with baricitinib was started, resulting in resolutionof erythema and pain.

Exceptfor an outbreak of labial herpes in patient 1, therapy with baricitinib waswell tolerated and no severe side-effects were recorded. Baricitinib improvedcutaneous lesions after only 4 weeks of treatment as assessed by the CutaneousDermatomyositis Area and Severity Index and the Dermatology Life Quality Index.

Thetype I IFN signature in the patients was demonstrated by upregulation of ISGsin blood and activation of p-JAK1 and p-STAT1 (signal transducer and activatorof transcription) in the skin of patients with DM. ISGs had decreased in theblood of patients 1 month after the initiation of baricitinib treatment. Invitro treatment of whole blood from patients with DM with baricitinib resultedin significant downregulation of IFI44 and IFI27 expression and thus confirmed thereduction of ISGs by JAK inhibition.

Panniculitisis a rare cutaneous complication in DM and has been described only once inassociation with NXP2 antibodies. The condition is generally hard to treat and does not respond aswell as muscle inflammation to immunosuppressive treatment. Here we provideclinical evidence of a beneficial effect of baricitinib in combination withIVIG in this rare but severe DM skin manifestation.

Inconclusion, inhibition of the JAK pathway with baricitinib can be an effective therapeuticapproach in adult DM with cutaneous manifestations including raremanifestations such as panniculitis.

Source- Fischer K, Aringer M,Steininger J, Heil J, Beissert S, Abraham S, Günther C. Improvement ofcutaneous inflammation and panniculitis in patients with dermatomyositis by theJanus kinase inhibitor baricitinib. Br J Dermatol. 2022 Sep;187(3):432-435.doi: 10.1111/bjd.21252. Epub 2022 May 20. PMID: 35318646.