Ruxolitinib-Associated Infections: Screening, Prevention, and Management
Infections Associated with Ruxolitinib
Ruxolitinib carries a clinically significant risk of serious infections, particularly herpes zoster, tuberculosis, hepatitis B reactivation, and opportunistic infections, requiring systematic screening before initiation and vigilant monitoring during treatment. 1
Primary Infectious Risks
Herpes Zoster (Most Common)
- Incidence rates: 3-4 per 100 patient-years in Western populations; up to 9 per 100 patient-years in Asian populations (Japan, Korea) 2
- Risk is 5-7 times higher than controls in polycythemia vera patients 3
- Dose-dependent relationship exists 2
- Risk factors include: age, female gender, prednisone >7.5 mg daily, concurrent infection, and hospitalization 2
Tuberculosis and Atypical Mycobacterial Infections
- TB reactivation risk similar to TNF inhibitors 2
- Cases reported in 3% of treated patients in some cohorts 4
- Both Mycobacterium tuberculosis and atypical mycobacteria (M. avium complex) documented 4
Hepatitis B Reactivation
- HBV-DNA titer increases reported in chronic HBV patients 1
- Can occur with or without transaminase elevations 1
- Multiple case reports documented 5
Opportunistic Infections
- Pneumocystis jirovecii pneumonia 6
- Cryptococcus neoformans pneumonia 7
- Toxoplasmosis retinitis (bilateral cases) 8
- Disseminated molluscum contagiosum 8
- Herpes simplex and cytomegalovirus reactivation 2
Other Serious Infections
- Lower respiratory tract infections (bronchitis 6.1%, pneumonia) 3
- Urinary tract infections (6%) 3
- Overall infection rate: 29.4-58.4 per 100 patient-years depending on indication 3
Pre-Treatment Screening Protocol
Mandatory Screening Tests
1. Tuberculosis Screening 2, 9
- Perform unless already completed before other biologic therapy without subsequent TB exposure
- Use tuberculin skin test or interferon-gamma release assay
- Obtain chest X-ray unless recently performed 2
- Initiate anti-TB therapy (isoniazid for 4-8 weeks minimum) in latent TB before starting ruxolitinib 9
2. Hepatitis B Virus Testing 2, 9
- Test all patients for: HBsAg, anti-HBs, anti-HBc
- If HBsAg positive (chronic infection): avoid ruxolitinib if possible; if unavoidable, consult hepatology and initiate antiviral prophylaxis (entecavir, tenofovir, or tenofovir alafenamide) 2
- If anti-HBc positive with negative HBsAg: obtain baseline HBV DNA to exclude occult infection 2
- If HBV DNA negative: monitor routinely for HBV DNA and HBsAg seroreversion per national TNF inhibitor guidelines 2
- If HBV DNA or HBsAg becomes positive during monitoring: stop ruxolitinib temporarily, refer to hepatology, initiate antiviral therapy, then reinstitute ruxolitinib 2
3. Hepatitis C Virus Testing 9
- Test HCV antibody in all patients
- If positive, obtain HCV RNA
- Treat HCV before initiating ruxolitinib with hepatologist involvement 9
4. Hepatitis D Testing 9
- Test in all patients with HBV infection 9
6. Varicella Zoster History 2
- Document history of varicella or zoster infection or immunization 2
7. Baseline Laboratory Tests 2
- Complete blood count with differential
- Liver enzymes (transaminases)
- Renal function tests
- Lipid levels (unless recently checked) 2
8. Physical Examination 2
- Baseline skin check for non-melanoma skin cancer in at-risk patients 2
- Document chronic or recurrent infections 2
- Assess for active infections 1
Vaccination Strategy
Pre-Treatment Vaccination
Herpes Zoster Vaccination 2, 9
- Recombinant vaccine (Shingrix - preferred): Can be given without stopping ruxolitinib; no contraindication with immunosuppression 2
- Live-attenuated vaccine (Zostavax): Requires 2-4 weeks cessation of ruxolitinib before vaccination; consider holding methotrexate for one dose to improve response 2, 9
- Evidence for Zostavax efficacy is questionable; recombinant vaccine preferred when available 2
- Influenza (annual) 8
- Pneumococcal vaccination 8
- Follow EULAR vaccination recommendations and national guidelines 2, 9
- Consider pausing methotrexate for 1-2 weeks at vaccination to reduce blunting of vaccine response 9
Contraindications and High-Risk Situations
Absolute Contraindications
- Active serious infection (including localized infections) 1
- Active tuberculosis 2
- Active hepatitis B or C (initiation not recommended) 1
Relative Contraindications - Careful Risk-Benefit Assessment Required 1
- Chronic or recurrent infection
- History of serious or opportunistic infection
- TB exposure history
- Residence or travel in endemic TB or mycoses areas
- Underlying conditions predisposing to infection
- Age >65 years (increased serious infection risk) 2
Avoid Combination Therapy 2
- Do not combine with biologic DMARDs, other JAK inhibitors, or potent immunosuppressants (cyclosporine, tacrolimus, azathioprine) due to excessive immunosuppression risk 2
Infection Prevention During Treatment
Herpes Zoster Prevention
Primary Prophylaxis
- Not routinely recommended for polycythemia vera patients 8
- Consider in high-risk patients (age, female, prednisone >7.5 mg daily) on individual basis 8
Secondary Prophylaxis
- Consider antiviral prophylaxis in patients with recurrent zoster 2
Patient Education
- Train patients to recognize cutaneous signs of herpes zoster 8
- Instruct to seek immediate medical attention if lesions develop (early treatment most effective) 8
Pneumocystis Prophylaxis
- Not routinely recommended for ruxolitinib monotherapy 10
- Consider trimethoprim-sulfamethoxazole in patients with multiple risk factors (high-dose steroids, combination immunosuppression) 10
COVID-19 Considerations
- Do not discontinue ruxolitinib during COVID-19 pandemic, especially in myeloproliferative neoplasms, as it may prevent immune cytokine release syndrome 11
- Consider deferring initiation of JAK inhibitors due to immunosuppressive effects during active pandemic 11
- Current recommendations do not support adjusting or discontinuing JAK inhibition to reduce COVID-19 risk 8
Monitoring During Treatment
Infection Surveillance
- Closely monitor for signs and symptoms of infection during and after treatment 1
- Monitor for TB development throughout treatment 1
- Routine monitoring for HBV DNA and HBsAg seroreversion in anti-HBc positive patients 2
Laboratory Monitoring
- Regular complete blood counts (cytopenias increase infection risk) 11
- Liver enzymes if hepatitis risk factors present 2
Management of Active Infections
General Principles
- Interrupt ruxolitinib if patient develops serious infection, opportunistic infection, or sepsis 1
- Do not resume until infection is controlled 1
Herpes Zoster Management
- Temporarily interrupt ruxolitinib treatment until episode resolves 2
- Initiate antiviral therapy promptly 8
- Consider secondary prophylaxis if recurrent episodes develop 2
Tuberculosis Management
- Stop ruxolitinib immediately 2
- Initiate anti-TB therapy per infectious disease consultation
- Do not resume until TB is controlled
Hepatitis B Reactivation
- Temporarily stop ruxolitinib until full evaluation 2
- Refer to hepatologist urgently 2
- Initiate antiviral therapy (entecavir, tenofovir, or tenofovir alafenamide) 2
- Ruxolitinib can be reinstituted once antiviral therapy established 2
Opportunistic Infections
- Interrupt ruxolitinib 1
- Initiate pathogen-specific therapy
- Consider infectious disease consultation
- Resume ruxolitinib only after infection controlled and with specialist input
Special Populations
Elderly Patients (>65 years)
- EMA restricts tofacitinib use due to increased serious infection risk 2
- Enhanced vigilance required for all JAK inhibitors in this age group 2
Patients on Corticosteroids
- Prednisone >7.5 mg daily increases herpes zoster risk 2
- Consider enhanced monitoring and lower threshold for prophylaxis 2