Can Rinvoq (upadacitinib) be taken in patients with a degenerative neurological disorder?

Upadacitinib (Rinvoq) in Patients with Degenerative Neurological Disorders

Upadacitinib (Rinvoq) should be used with extreme caution in patients with degenerative neurological disorders, and in most cases, alternative treatment options should be considered first due to potential safety concerns.

Mechanism and Approval Context

Upadacitinib is a selective Janus kinase 1 (JAK1) inhibitor that works by blocking the JAK-STAT intracellular signal transduction pathway. This pathway is important in the response to multiple cytokines, including those involved in inflammatory conditions 1.

• FDA-approved for:
  • Moderate-to-severe atopic dermatitis (after failure of other systemic therapies)
  • Rheumatoid arthritis
  • Certain inflammatory bowel diseases

Safety Concerns Relevant to Neurological Disorders

Major Safety Signals

1. Thromboembolic Events

   • Venous thromboembolism and pulmonary embolism have been reported in clinical trials 2
   • These events are particularly concerning for patients with degenerative neurological disorders who may have reduced mobility

2. Serious Infections

   • Higher rates of serious infections compared to placebo 2, 3
   • Herpes zoster reactivation is significantly more common with upadacitinib than with comparator treatments 3, 4
   • Patients with neurological disorders may already have compromised immune function or swallowing difficulties

3. Cardiovascular Events

   • FDA warnings include increased risk of serious heart-related events 1
   • One case of nonfatal stroke was reported in the upadacitinib group in a clinical trial 5
   • Many degenerative neurological disorders have comorbid cardiovascular issues

4. Neurological Considerations

   • No specific studies have evaluated upadacitinib in patients with pre-existing degenerative neurological disorders
   • The FDA has applied warnings of increased risk of serious heart-related events, cancer, blood clots, and death for the JAK inhibitor class 1

Decision Algorithm for Upadacitinib Use in Patients with Degenerative Neurological Disorders

1. First-line consideration: Use alternative therapies with established safety profiles in neurological disorders

   • For atopic dermatitis: Consider dupilumab or tralokinumab first 1
   • For rheumatoid arthritis: Consider TNF inhibitors or abatacept first

2. If alternative therapies fail:

   • Complete thorough neurological assessment to establish baseline
   • Evaluate for specific contraindications:
     • History of thromboembolism
     • Cardiovascular disease
     • Impaired mobility
     • Immunocompromise
     • Swallowing difficulties

3. If proceeding with upadacitinib:

   • Start with lowest effective dose (15 mg daily rather than 30 mg) 1, 3
   • Implement strict monitoring:
     • Complete blood count with differential
     • Liver enzymes at baseline and after initiation
     • Lipid panel after initiation
     • Regular neurological assessments
     • Vigilance for infection signs

4. Discontinue immediately if:

   • Worsening of neurological symptoms
   • Signs of thromboembolism
   • Serious infection
   • Significant laboratory abnormalities

Common Pitfalls and Caveats

1. Failure to vaccinate before initiation

   • Patients should receive any needed live vaccines before starting upadacitinib 1
   • Consider recombinant zoster vaccine for adults at risk of herpes zoster

2. Inadequate monitoring

   • Laboratory monitoring is essential:
     • Complete blood count with differential
     • Liver enzymes
     • Lipid panel
   • The optimal frequency of ongoing lab monitoring for continuous JAK inhibitor use remains unclear 1

3. Overlooking drug interactions

   • Many patients with degenerative neurological disorders are on multiple medications
   • Evaluate for potential drug interactions before initiating therapy

4. Ignoring early warning signs

   • Promptly address any new neurological symptoms, infections, or laboratory abnormalities

Conclusion

While upadacitinib has demonstrated efficacy in inflammatory conditions, its safety profile raises significant concerns for patients with degenerative neurological disorders. The risks of thromboembolic events, serious infections, and cardiovascular complications may be amplified in this vulnerable population. Alternative therapies with better established safety profiles should be considered first-line options whenever possible.