Is RINVOQ (upadacitinib) considered an immunosuppressant?

RINVOQ (Upadacitinib) is Classified as an Immunosuppressant

Yes, RINVOQ (upadacitinib) is definitively classified as an immunosuppressant medication due to its mechanism of action as a JAK inhibitor that modulates immune system function.

Mechanism of Action and Classification

Upadacitinib functions as a selective Janus kinase (JAK) inhibitor with preferential selectivity for JAK1 1. This mechanism works by:

• Blocking signaling of multiple inflammatory cytokines that rely on the JAK-STAT pathway
• Reducing immunopathogenic gene expression induced by type 1 interferons
• Inhibiting phosphorylation of downstream effector proteins that mediate cytokine signaling 2

These actions directly suppress immune system function, which is the defining characteristic of immunosuppressant medications.

Evidence Supporting Immunosuppressant Classification

FDA Labeling and Warnings

The FDA label for RINVOQ explicitly recognizes its immunosuppressive properties through multiple black box warnings related to:

• Serious infections: Patients treated with RINVOQ are at increased risk of serious bacterial, fungal, viral, and opportunistic infections 3
• Immunosuppression-related malignancies: The FDA warns about increased risk of lymphoma and other malignancies 3
• Requirement for TB screening: Prior to initiating RINVOQ, patients must be evaluated for active and latent tuberculosis infection 3

Clinical Guidelines Recognition

Multiple clinical guidelines classify JAK inhibitors including upadacitinib as immunosuppressants:

• The American College of Rheumatology/American College of Chest Physicians guideline (2024) lists upadacitinib among immunosuppressive medications requiring specific monitoring for immunosuppression-related complications 4
• The ECCO guidelines on Crohn's disease therapeutics (2024) position upadacitinib alongside other immunosuppressive agents 4
• The AGA guidelines (2024) note that JAK inhibitors like upadacitinib may be associated with immunosuppression-related infections and should be avoided in certain populations at higher risk 4

Clinical Implications of Immunosuppressant Status

The immunosuppressant classification of RINVOQ has important clinical implications:

• Infection risk monitoring: Patients require screening for tuberculosis, hepatitis B, and hepatitis C prior to initiation 4
• Laboratory monitoring: Regular CBC with differential and CMP at baseline, 4-8 weeks after starting, and every 3 months thereafter 4
• Contraindications: Not recommended for use in combination with other JAK inhibitors, biologic DMARDs, or potent immunosuppressants such as azathioprine and cyclosporine 3
• Pregnancy considerations: Limited safety data in pregnancy, and should be avoided in women contemplating pregnancy 4

Safety Profile Related to Immunosuppression

The immunosuppressive effects of upadacitinib contribute to specific safety concerns:

• Serious infections: Including bacterial, fungal, viral, and opportunistic infections
• Herpes zoster reactivation: Higher rates observed with longer duration of exposure 5
• Neutropenia: Meta-analysis shows significantly higher risk compared to placebo (RR = 5.63) 6
• Cardiovascular events: FDA black box warning regarding major adverse cardiovascular events in patients with risk factors 3

Conclusion

Based on its mechanism of action, FDA labeling, clinical guideline classifications, and safety profile, RINVOQ (upadacitinib) is definitively classified as an immunosuppressant medication. This classification has important implications for patient monitoring, risk assessment, and clinical decision-making when prescribing this medication.