What are the side effects of Baricitinib (Janus kinase inhibitor)?

Side Effects of Baricitinib

Baricitinib is associated with several significant side effects including increased risk of infections (particularly herpes zoster), thromboembolism, laboratory abnormalities, and gastrointestinal perforations, requiring careful patient selection and monitoring during treatment. 1

Common Side Effects

• Infections:

  • Upper respiratory tract infections are among the most common adverse events 1
  • Herpes zoster (shingles) infection occurs at higher rates compared to placebo (4.4 per 100 patient-years with 4 mg dose; 3.1 per 100 patient-years with 2 mg dose) 2
  • Opportunistic infections including herpes simplex, herpes zoster, and tuberculosis have been reported 1

• Laboratory Abnormalities:

  • Lymphopenia and neutropenia may occur 1
  • Creatinine phosphokinase (CPK) elevations, occasionally with myalgia 1
  • Creatinine increases without organ dysfunction 1
  • Lipid elevations (LDL cholesterol) 1, 3
  • Liver enzyme elevations 1

Serious Side Effects

• Thromboembolism:

  • Venous thromboembolism (VTE) risk is increased, particularly with the 4 mg dose 1
  • The European Medicines Agency (EMA) has updated the baricitinib label with a warning for patients at risk of thromboembolic disease 1
  • Incidence of VTE in long-term studies is approximately 0.5 per 100 patient-years 2
  • Risk factors include age >65, obesity, history of VTE, and use of Cox-2 inhibitors 1

• Gastrointestinal Perforations:

  • Reported in clinical trials with baricitinib 1
  • Higher risk in patients with history of diverticulitis and those taking concomitant NSAIDs or glucocorticoids 1

• Serious Adverse Events:

  • Higher incidence with 4 mg dose compared to 2 mg dose at 24 weeks (RR 1.84; 95% CI 1.02-3.30) 4

Monitoring Recommendations

Based on expert guidelines, the following monitoring is recommended during baricitinib treatment 1, 5:

1. Before starting treatment:

   • Complete blood count with differential
   • Liver function tests
   • Renal function assessment
   • Lipid profile
   • Tuberculosis screening
   • Hepatitis B and C testing
   • VTE risk assessment

2. During treatment:

   • Blood count and differential at 1 month, 3 months, then every 3 months
   • Transaminases and renal function at same intervals
   • Lipid levels at 3 months
   • Monitor for signs of infection

3. Laboratory parameters requiring action 1:

   • Absolute neutrophil count <1000/mm³: Consider dose reduction or temporary cessation
   • Absolute lymphocyte count <750/mm³: Consider dose reduction or temporary cessation
   • Hemoglobin decrease >20g/L or level <80g/L: Interrupt treatment until normalized

Special Considerations

• Patients at higher risk for complications:

  • Elderly patients (>65 years)
  • Patients with history of VTE
  • Patients with cardiovascular risk factors
  • Those with history of diverticulitis
  • Patients with renal impairment (dose adjustment required)
  • Patients with severe hepatic impairment (contraindicated in Child-Pugh C) 1

• Pregnancy and lactation:

  • Avoid use in women contemplating pregnancy due to limited safety data 5

Practical Approach to Management

1. Assess patient risk factors before initiating therapy
2. Use lower dose (2 mg) in patients with risk factors for thrombosis
3. Implement appropriate laboratory monitoring schedule
4. Vaccinate patients against herpes zoster before starting treatment if possible
5. Temporarily discontinue during serious infections
6. Monitor for signs of VTE and gastrointestinal complications

Baricitinib has generally been well-tolerated in clinical trials with most adverse events being mild to moderate in severity 1, 2, but the specific risks outlined above require vigilance and appropriate patient selection to optimize safety.