Upadacitinib in Indian Context: Evidence-Based Recommendations
Critical Note on Indian-Specific Data
No India-specific clinical trial data for upadacitinib exists in the current evidence base. The following recommendations are based on international guidelines and global clinical trials that included diverse populations, with dosing and safety protocols applicable to Indian patients 1, 2, 3.
Approved Indications and Dosing
Rheumatoid Arthritis
- Administer upadacitinib 15 mg orally once daily, either as monotherapy or combined with methotrexate 2, 3.
- This dose demonstrates superior efficacy compared to adalimumab plus methotrexate in head-to-head trials, particularly for ACR50/70 responses 3.
- The 30 mg dose is NOT approved for rheumatoid arthritis and carries increased safety risks 2, 3.
Atopic Dermatitis
- Use 15 mg once daily for moderate disease or 30 mg once daily for severe disease based on EASI score severity 2.
- The 30 mg dose shows highest efficacy for reducing EASI scores but requires careful cardiovascular risk assessment 2.
Ulcerative Colitis
- Induction: 45 mg once daily for 8 weeks 1, 2.
- Maintenance: 15 mg or 30 mg once daily after achieving clinical response 1, 2.
- High certainty evidence shows large benefit for both induction and maintenance of remission, including in biologic-exposed patients 1.
Psoriatic Arthritis
- Standard dose is 15 mg once daily 2.
Pre-Treatment Screening Requirements
Mandatory Baseline Testing
- Tuberculosis screening with IGRA or tuberculin skin test (critical in Indian population with high TB prevalence) 3.
- Complete blood count with differential 2, 3.
- Liver function tests (AST, ALT, bilirubin) 2, 3.
- Renal function tests (serum creatinine, eGFR) 2, 3.
- Lipid panel (total cholesterol, LDL, HDL, triglycerides) 2, 3.
- Hepatitis B surface antigen and anti-HBc antibody 2, 3.
- Hepatitis C antibody 2, 3.
- Pregnancy test in women of childbearing potential 2.
Recommended Vaccination
- Herpes zoster vaccination before initiating therapy in patients ≥18 years, given increased HZ risk with JAK inhibitors 3, 4, 5.
Absolute Contraindications
- Severe hepatic impairment (Child-Pugh C) 2, 3.
- Active serious infections including active tuberculosis 3.
- Current malignancies 1.
- Pregnancy and lactation 2.
- Patients with history of major adverse cardiovascular events or stroke who are ≥50 years with cardiovascular risk factors 1.
High-Risk Populations Requiring Extreme Caution
European Medicines Agency Risk Stratification
JAK inhibitors should be used with extreme caution or avoided in 1:
- Patients ≥65 years of age
- Current smokers or those with long smoking history
- Patients with cardiovascular risk factors
- Those at increased risk of malignancy
- Patients with risk factors for venous thromboembolism (VTE)
Dose Reduction Strategy for High-Risk Patients
- In patients with VTE risk factors, cancer risk, or major cardiovascular risk, use the lowest effective maintenance dose (15 mg for UC maintenance rather than 30 mg) 1.
Monitoring Protocol
Initial Phase (First 3 Months)
- CBC with differential at baseline and 4 weeks after initiation 2.
- Liver enzymes at baseline and 4 weeks 2.
- Lipid panel at 12 weeks after initiation 2.
Ongoing Monitoring
- Regular CBC with differential and liver enzymes 2.
- Monitor for signs of VTE: chest pain, leg swelling, shortness of breath 2.
- Monitor for herpes zoster infections (higher risk with upadacitinib compared to placebo) 4, 5.
- Assess for serious infections, particularly in patients >65 years 3.
Dose Adjustments
Renal Impairment
- No dose adjustment required for any degree of renal impairment, including severe renal disease 2, 3.
Hepatic Impairment
- No adjustment needed for mild to moderate hepatic impairment 2.
- Contraindicated in severe hepatic impairment 2, 3.
Drug Interactions
- Reduce dose when co-administered with strong CYP3A4 inhibitors 3.
- May require dose increase with rifampin or other strong CYP3A4 inducers 3.
- No significant interactions with methotrexate 2.
Safety Profile and Adverse Events
Common Adverse Events
- Acne, nasopharyngitis, headache, anemia 4.
- Creatine phosphokinase elevation (usually asymptomatic) 4, 6.
- Upper respiratory tract infections 4.
- Arthralgia 4.
Serious Adverse Events of Special Interest
- Herpes zoster infections (more frequent than placebo, mostly non-serious cases) 4, 5, 6.
- Venous thromboembolism (limited proportion but requires vigilance) 4, 5.
- Hyperlipidemia (requires lipid monitoring) 1.
- Serious infections similar to biologics, higher in patients >65 years 3.
Alternative Therapies by Indication
For Rheumatoid Arthritis
- Conventional synthetic DMARDs: methotrexate, leflunomide, sulfasalazine 3.
- Biologic DMARDs: adalimumab, etanercept, infliximab, tocilizumab 3.
- Other JAK inhibitors: tofacitinib 5 mg twice daily, baricitinib 2-4 mg once daily 7.
For Ulcerative Colitis
- Biologic therapies: infliximab, adalimumab, vedolizumab, golimumab 1.
- Other JAK inhibitor: tofacitinib 10 mg twice daily for induction, then 5 mg twice daily for maintenance 7.
- Filgotinib 200 mg once daily (26% clinical remission at week 10 vs 15% placebo in biologic-naive patients) 1.
For Atopic Dermatitis
- Dupilumab (IL-4/IL-13 inhibitor) 7.
- Other JAK inhibitors: abrocitinib 100-200 mg once daily 7.
- Conventional immunosuppressants: cyclosporine, methotrexate, azathioprine 7.
Critical Pitfalls to Avoid
- Never use 30 mg dose for rheumatoid arthritis - only 15 mg is approved and safe 2, 3.
- Do not initiate during active infections - complete TB screening and treat latent TB before starting 3.
- Do not combine with other biologics or potent immunosuppressants beyond established methotrexate combination 3.
- Do not overlook cardiovascular risk stratification - FDA black box warnings apply based on ORAL surveillance study showing increased MACE and malignancy in high-risk RA patients 2.
- Do not administer live vaccines during treatment 7.
- Do not ignore smoking status - current or long-term past smokers are at significantly higher risk for adverse events 1.