Off-Label Use of JAK Inhibitors in Orphan Diseases and Other Conditions? Save

The issues surrounding publication bias are real.

Several positive, uncontrolled case series suggest that JAK inhibitors (JAKi) may be effective in:

• Inflammatory myositis – including skin involvement, muscle disease, and calcinosis
• Uveitis
• Connective tissue disease-associated interstitial lung disease (CTD-ILD)
• Systemic lupus erythematosus  – phase 3 studies of upadacitinib and deucravacitinib are ongoing, and baricitinib has shown negative results in a phase 3 randomized controlled trial

The perceived benefits reported in case studies must be interpreted cautiously for several reasons:

1. These studies often lack comparison.
2. Published data typically represent the "best" cases.
3. Follow-up durations are frequently short, limiting the understanding of long-term benefits and risks.

When should you consider off-label use of JAKi?

Off-label use of JAK inhibitors should be guided by careful consideration and patient-centered communication. Tips:

1. Use after failure or contraindication of usual approved or conventionally used drugs.
2. Inform the patient that this treatment is not approved for the specific indication but there could be a suggestion of some benefit from small uncontrolled studies.

At the ACR this year, multiple abstracts hold potential promise for rare conditions, including benefit from unapproved (and not fully proven) treatments including the use of JAK inhibitors. Examples include:

• Inflammatory myositis: Baricitinib demonstrated positive benefit in treatment-refractory inflammatory myopathies (Abstract #1731).
• MDA5-associated ILD: Upadacitinib showed promise in managing this severe lung disease (Abstract #0348).

Stay tuned as more data emerges.