Ruxolitinib

Author Information

An event is serious (based on the ICH definition) when the patient outcome is:

• * death

• * life-threatening

• * hospitalisation

• * disability

• * congenital anomaly

• * other medically important event

In a case series of 3 children, a 7-year-old girl developed viral respiratory infections following off label treatment with ruxolitinib for stimulator of interferon genes (STING) associated vasculopathy with onset in infancy (SAVI).

The girl presented at the age of 3 months with growth failure and respiratory distress. Livedo reticularis was observed on her lower limbs. She needed several ICU admissions for ventilator support during bronchiolitis and pneumonia. Extensive ground glass abnormalities and chronic Pseudomonas aeruginosainfection were documented. Lung biopsy revealed interstitial fibrosis. Therapy with steroids [specific drugs not stated] were only partially effective, and association of infliximab and methotrexate were ineffective. Additionally, cheeks and nose telangiectatic skin lesions and unilateral vocal cord paresis were noted. Her total IgA and IgG were elevated, along with mild lymphopenia. She was found positive for peripheral blood type I interferon signature. At the age of 7-years, she started receiving off label ruxolitinib 0.25 mg/kg daily in two doses, which was progressively increased to 0.7 mg/kg daily. However, starting from 7 months of therapy, she started to experience an increase in hospitalisation due to viral respiratory infections caused by several episodes of rhinovirus infection, influenza A, varicella, coronavirus and exacerbation of underlying Pseudomonas aeruginosainfection [outcomes not stated]. Infection due to coronavirus needed mechanical ventilation and extracorporeal membrane oxygenation for 11 days.

The girl's therapy with ruxolitinib was reduced. Thereafter, she was started on antibiotic prophylaxis with cotrimoxazole [Bactrim] and azithromycin; however, it did not prevent the febrile episodes. She was on immune globulin prophylaxis and no severe infections were noted at the time of this report (at the age of 10 years).

Author comment: "[We] observed several episodes of severe viral infections in one patient, suggesting the possibility that JAK inhibitors might significantly increase the risk of infections possibly in cases of more severe lung involvement or in the presence of genetic modifiers, not investigated in our patient". "[P]atients with peripheral blood type I IFN signature. The JAK1/2 inhibitor ruxolitinib was administered on an off-label basis."