Interferon Requirements Before Starting JAK Inhibitors
No specific interferon treatment is required before starting JAK inhibitors, but patients should be screened for tuberculosis and receive appropriate vaccinations, particularly against herpes zoster, prior to JAK inhibitor initiation.
Pre-JAK Inhibitor Screening and Vaccination Requirements
- Tuberculosis (TB) testing is recommended before starting JAK inhibitors due to potential vulnerability to Mycobacterium tuberculosis infection; IFN-gamma release assays are preferred for TB screening 1
- Vaccination is an important tool for infection prevention in patients starting JAK inhibitors, with specific recommendations for completion before treatment initiation 1
- Inactivated pneumococcal, influenza, and a two-dose Shingrix (recombinant zoster vaccine) series should be administered prior to JAK inhibitor therapy for patients aged >18 years 1
- If the inactivated recombinant zoster vaccine (Shingrix) is not available, the live zoster vaccine (Zostavax) must be administered at least 3-4 weeks before initiating JAK inhibitors 1
Rationale for Pre-JAK Inhibitor Precautions
- JAK1/2 inhibition affects cellular cytotoxicity by blocking interferon-γ signaling, inhibiting cellular killing mechanisms and impairing the ability to fight infectious agents 1
- Herpes zoster (HZ) is an established complication of JAK inhibitors, with prevalence <3% in atopic dermatitis patients on oral JAK inhibitors 1
- JAK inhibitors are associated with increased risk of serious infections, venous thromboembolism, and malignancy in asymptomatic patients 2
- The European Task Force on Atopic Dermatitis recommends a 1-week pause of JAK inhibitor treatment after COVID-19 vaccination to prevent insufficient vaccination response 1
Special Considerations for Different Patient Populations
- For patients with moderate-to-severe ulcerative colitis, JAK inhibitors (tofacitinib, upadacitinib) have varying recommendations for first-line use in different regions of the world 1
- In the United States, FDA labeling recommends JAK inhibitors only after failure or intolerance to TNF antagonists 1
- In Europe, the European Medicines Agency recommends cautious use of JAK inhibitors as first-line agents in patients at risk for adverse cardiovascular outcomes 1
- Patients with comorbid heart, liver, or kidney conditions should be carefully selected for JAK inhibitor treatment, with appropriate dose adjustments for renal or hepatic impairment 1
Risk Assessment Before JAK Inhibitor Initiation
- Prior to initiating JAK inhibitors, consider venous thromboembolism (VTE) risk factors including history of VTE, age >65 years, inherited thrombophilias, exogenous estrogen use, recent surgery, immobility, and other cardiovascular risk factors 1
- JAK inhibitors should not be used for patients with severe hepatic disease (Child-Pugh C), although no dosage adjustment is needed for mild or moderate hepatic impairment 1
- Renal function significantly affects JAK inhibitor exposure; baricitinib and abrocitinib are not recommended in patients with severe renal impairment (eGFR <30 mL/min) 1
- Laboratory monitoring is required for all JAK inhibitors due to potential safety issues 1
Common Pitfalls and Precautions
- Avoid unnecessary JAK inhibitor therapy in asymptomatic patients due to potential serious adverse effects 2
- Do not delay tuberculosis testing when anti-TNF-α agents are needed for management of acute severe or refractory immune-related adverse events 1
- Recognize that JAK inhibitors can impair immune responses to vaccines; ideally complete vaccination series prior to JAK inhibitor initiation 1
- Be aware that JAK inhibitors may increase risk of malignancy, with all having boxed warnings for this potential safety issue 1