What are the infection risks associated with Risankizumab (Risankizumab) treatment?

Infection Risks Associated with Risankizumab Treatment

Risankizumab demonstrates a favorable infection safety profile with predominantly mild-to-moderate upper respiratory tract infections and no significant increase in serious infections compared to other biologics. 1

Overall Infection Risk Profile

The infection rate with risankizumab is modest and comparable to placebo in clinical trials. In the INSPIRE trial for ulcerative colitis, infections occurred at a rate of 18.5% with risankizumab versus 6.2% with placebo 1. However, this represents a relative risk of 3.30, which is primarily driven by non-serious infections 1.

Key Infection Characteristics:

• Most infections are non-serious upper respiratory tract infections (nasopharyngitis being most common) that do not require treatment discontinuation 2, 3
• Serious infection rate is low at 1.2 per 100 patient-years in long-term safety data from 17 clinical trials involving 3,072 patients with up to 5.9 years of exposure 4
• No unique or unexpected infection patterns have emerged with risankizumab compared to other biologics 1

Specific Infection Types

Upper Respiratory Tract Infections

• Upper respiratory infections are the most frequently reported adverse event across all risankizumab trials 2, 3
• These infections are typically mild-to-moderate in severity and self-limiting 4
• COVID-19 infection was reported in 8.6% and nasopharyngitis in 5.7% of patients in recent studies 5

Serious Infections

• Serious infections occur at a rate of 1.2 per 100 patient-years with long-term treatment 4
• This rate is comparable to or lower than other biologics used for inflammatory conditions 1
• One case of fatal urosepsis was reported in the KEEPsAKE 1 trial (deemed unrelated to study drug) 3

Opportunistic Infections

• As an IL-23 inhibitor, risankizumab may have a lower rate of opportunistic infections compared to TNF antagonists 6
• No significant increases in mycobacterial or fungal infections have been reported 1, 4
• Enteric infections may occur but are not increased compared to placebo 1

Risk Factors for Infections on Risankizumab

Patient-Related Factors:

• Age >65 years increases infection risk with any immunosuppressive therapy 1
• Malnutrition (OR 2.31) and obesity (OR 1.07 per kg/m²) independently increase infection risk 1
• Active disease increases infection risk by 30% per 100-point increase in disease activity scores 1

Treatment-Related Factors:

• Combination therapy with other immunosuppressants significantly increases infection risk (OR increases from 2.9 for monotherapy to 14.5 for triple therapy) 1
• Risankizumab monotherapy carries moderate immunosuppression risk, lower than TNF inhibitors or combination therapies 1
• Concomitant corticosteroids increase risk of fungal infections (Candida) 1

Monitoring and Prevention Strategies

Baseline Screening Required:

• Test for latent tuberculosis (PPD or QuantiFERON-Gold) before initiating therapy 1
• Screen for hepatitis B and C (HBsAg, anti-HBs Ab, anti-HBc Ab, HCV antibody) 1
• HIV testing should be considered based on individual risk factors 1
• Complete blood count and metabolic profile 1

Ongoing Monitoring:

• Yearly tuberculosis testing in high-risk patients (those with TB exposure through travel, work, or family contact) 1
• Periodic history and physical examination with screening for infections 1
• For patients not at high risk, TB screening frequency is at clinician discretion 1

Contraindications and Treatment Interruption:

• Absolute contraindication: clinically important active infection 1
• Temporarily discontinue risankizumab for febrile illness requiring antibiotics 1
• Treatment can be restarted after complete resolution of infection and completion of antibiotic course 1
• Consider repeating loading doses if >3-4 half-lives have passed since the previous dose 1

Special Considerations

Tuberculosis Management:

• Do not administer risankizumab to patients with active tuberculosis 1
• Consider anti-tuberculosis therapy before starting risankizumab in patients with latent TB 1

Immunosuppression Potential:

• Risankizumab may cause immunosuppression in utero-exposed infants 7
• Delay live virus vaccinations in infants exposed in utero for at least 5 months after birth due to the drug's half-life 7
• Risks and benefits should be considered before administering live vaccines to exposed infants 7

Comparative Safety:

• Risankizumab demonstrates no increased infection risk compared to IL-17 inhibitors (secukinumab, ixekizumab) in switching studies 5
• Long-term exposure data (up to 5.9 years) shows no increase in exposure-adjusted adverse event rates (318 vs 171 events per 100 PY for short- vs long-term) 4
• Cardiometabolic comorbidities do not increase infection risk with risankizumab treatment 8

Common Pitfalls to Avoid

• Do not overlook baseline TB screening, as reactivation can occur with any immunosuppressive therapy 1
• Do not combine with multiple immunosuppressants without careful consideration, as this dramatically increases infection risk 1
• Do not dismiss mild upper respiratory infections as insignificant—monitor for progression to serious infection 4
• Do not restart therapy immediately after infection resolution—ensure complete resolution and antibiotic course completion 1