Is Upadacitinib (Rinvoq) safe to use in a patient with diabetes mellitus and a history of gastritis?

Upadacitinib Safety in Patients with Diabetes and Gastritis

Upadacitinib can be used in patients with diabetes mellitus and a history of gastritis, as neither condition represents a contraindication to therapy, though careful monitoring is warranted. 1, 2

Key Safety Considerations

Diabetes Mellitus

• Diabetes is not a contraindication to upadacitinib therapy. 2
• No dose adjustment is required for patients with diabetes mellitus. 2
• Monitor for potential metabolic effects including hyperlipidemia and hypercholesterolemia, which occur in 2-4% of patients across inflammatory bowel disease trials. 2
• Baseline and periodic lipid profile monitoring is recommended as part of standard JAK inhibitor surveillance. 1

Gastritis History

• A history of gastritis does not preclude upadacitinib use. 2
• Unlike NSAIDs, JAK inhibitors do not have direct gastric mucosal toxicity as a primary mechanism. 3
• In inflammatory bowel disease trials where gastrointestinal monitoring was intensive, upper gastrointestinal adverse events were not prominently reported. 2
• Abdominal pain was reported in <3% of patients across ulcerative colitis and Crohn's disease trials, similar to placebo rates. 2

Absolute Contraindications to Consider

The following are true contraindications where upadacitinib should NOT be used: 1, 2

• Active serious infections
• Severe hepatic impairment (Child-Pugh C)
• Pregnancy (limited safety data)
• Concurrent use with other JAK inhibitors, biologic immunomodulators, or potent immunosuppressants

Pre-Treatment Requirements

Before initiating upadacitinib, complete the following: 1

• Test and treat latent tuberculosis if positive
• Administer herpes zoster vaccination (critical given increased infection risk)
• Complete all needed live vaccines before treatment
• Baseline laboratory assessment: complete blood count with differential, comprehensive metabolic panel including liver enzymes, renal function, and lipid profile
• Screen for hepatitis B and C

Dose Modifications Based on Comorbidities

Adjust dosing in the following scenarios: 1, 2

• Severe renal impairment (CrCl <30 mL/min): Maximum dose 15 mg daily
• Age ≥75 years: Consider lower dosing (context-dependent on indication)
• Moderate renal impairment (CrCl 30-60 mL/min): May require dose reduction depending on indication

High-Risk Populations Requiring Caution

Exercise extreme caution or avoid upadacitinib in patients with: 3, 1

• Age ≥65 years with cardiovascular risk factors (smoking history, prior cardiovascular disease)
• Current or long-term previous smokers
• History of major adverse cardiovascular events (myocardial infarction, stroke)
• History of malignancy
• Risk factors for venous thromboembolism

The FDA has applied class-wide black box warnings for JAK inhibitors based on increased risks of major adverse cardiovascular events, venous thromboembolism, malignancies, and death in patients ≥50 years with cardiovascular risk factors. 1

Monitoring During Therapy

Implement the following surveillance schedule: 1, 2

• Periodic complete blood counts (monitor for neutropenia, lymphopenia, anemia)
• Liver function tests (elevated transaminases occur in 2-4% of patients)
• Lipid profiles (hyperlipidemia and hypercholesterolemia are common)
• Creatine phosphokinase levels (elevation occurs in 3-8% of patients)
• Clinical assessment for infections, particularly herpes zoster

Common Adverse Events

The most frequently reported adverse events include: 2, 4

• Upper respiratory tract infections (9-20%)
• Acne (2-6%)
• Herpes zoster (2-5%)
• Elevated creatine phosphokinase (3-8%)
• Neutropenia (1-5%)
• Hyperlipidemia/hypercholesterolemia (2-4%)

Serious infections occur at rates of 4-9 per 100 patient-years, with herpes zoster being the most notable infection risk requiring prophylactic vaccination. 5, 4

Clinical Efficacy Context

Upadacitinib demonstrates robust efficacy across multiple immune-mediated inflammatory diseases: 3

• For atopic dermatitis: Strong recommendation with moderate certainty evidence at 15-30 mg daily 3, 1
• For ulcerative colitis: High certainty for large benefit in induction (45 mg) and maintenance (15-30 mg) 3
• For Crohn's disease: Clinical remission rates of 70-85% by week 8-12 6, 7
• For rheumatoid arthritis: Superior efficacy to adalimumab in head-to-head trials at 15 mg daily 3

Real-world data confirm rapid onset of action, with clinical responses observed as early as week 2 in both ulcerative colitis (36% remission) and Crohn's disease (56% remission). 6