What is the recommended dose of upadacitinib (Rinvoq) for a patient with moderate to severe psoriasis?

Recommended Dose of Upadacitinib for Moderate to Severe Psoriasis

For moderate to severe psoriasis, upadacitinib 15 mg once daily is the recommended dose, though this remains an off-label use as upadacitinib is not FDA-approved for psoriasis. 1

FDA-Approved Dosing for Related Conditions

While upadacitinib lacks FDA approval specifically for plaque psoriasis, the FDA-approved dosing for psoriatic arthritis provides the most relevant guidance:

• Standard dose: 15 mg once daily for psoriatic arthritis 1
• The 30 mg dose has been studied but is not the recommended dose for psoriatic arthritis despite showing superior efficacy 1, 2

Evidence Supporting 15 mg Dosing in Psoriasis

Psoriatic Arthritis Data (Most Relevant)

• In patients with psoriatic arthritis, 52.3% achieved PASI75 at one year with 15 mg daily 3
• At 12 weeks, 52% achieved ASAS 40 response in ankylosing spondylitis trials 4
• The 15 mg dose demonstrated 70.6% ACR20 response at week 12, which was noninferior to adalimumab 2

Higher Dose Considerations

• The 30 mg dose showed 78.5% ACR20 response and was superior to adalimumab 2
• However, adverse events were more frequent at 30 mg (72.3%) compared to 15 mg (66.9%) 2
• Serious infections occurred in 2.6% with 30 mg versus 1.2% with 15 mg 2
• Hepatic disorders were more common at 30 mg (12.3%) versus 15 mg (9.1%) 2

Dose Adjustments for Special Populations

Renal Impairment

• Maximum 15 mg daily for severe renal impairment (creatinine clearance <30 mL/min) 4
• No adjustment needed for mild-to-moderate renal impairment 4

Hepatic Impairment

• No dosage adjustment for mild or moderate hepatic impairment (Child-Pugh A/B) 4
• Contraindicated in severe hepatic disease (Child-Pugh C) 4

Critical Safety Considerations

Baseline Contraindications

Do not initiate if: 1

• Lymphocyte count <500 cells/mm³
• Absolute neutrophil count <1,000 cells/mm³
• Hemoglobin <9 g/dL

Mandatory Discontinuation Thresholds

Stop immediately if: 5

• Hemoglobin <8 g/dL or drops >2 g/dL
• ANC <500/mm³
• Lymphocyte count <500/mm³

Age and Cardiovascular Risk

• Increased serious infection risk in patients ≥65 years 5
• Five-fold increased pulmonary embolism risk with higher doses compared to TNF inhibitors 6, 5
• Increased major adverse cardiovascular events in patients >50 years with cardiovascular risk factors 5

Clinical Context and Limitations

Important caveat: Upadacitinib is not FDA-approved for plaque psoriasis 3. The evidence base consists primarily of:

• Psoriatic arthritis trials where skin outcomes were secondary endpoints 1, 2
• Case series showing complete remission in overlapping psoriasis/atopic dermatitis 3
• Phase 2 ankylosing spondylitis data 4

No phase 3 trials have evaluated upadacitinib specifically for plaque psoriasis 3, making this an off-label use that requires informed consent and careful patient selection.

Practical Algorithm

1. Confirm patient is appropriate candidate:

   • Age <65 years (or carefully weigh risks if older) 5
   • No cardiovascular risk factors or history of VTE 5
   • No active serious infections 1
   • Baseline labs meet minimum thresholds 1

2. Initiate at 15 mg once daily 1

3. Monitor closely:

   • CBC and liver function at 1-2 months, then every 3-4 months 5
   • Lipid panel at 1-2 months 5
   • Discontinue if safety thresholds breached 5

4. Consider alternative therapies first: Given the lack of FDA approval for psoriasis and significant safety concerns, FDA-approved biologics targeting IL-17, IL-23, or TNF-α should generally be prioritized over off-label upadacitinib 4