With polymyositis and an interstitial lung disease (ILD) exacerbation, should I discontinue mycophenolate and the JAK inhibitor (e.g., upadacitinib)?

Do NOT Stop Mycophenolate or JAK Inhibitor During Polymyositis-ILD Exacerbation

In polymyositis with ILD exacerbation, you should continue mycophenolate and intensify therapy by adding other agents rather than discontinuing current immunosuppression. Stopping these medications during an acute exacerbation would remove disease control and worsen outcomes.

Rationale for Continuing Current Therapy

The 2023 ACR/CHEST guidelines for SARD-ILD (which includes IIM-ILD/polymyositis-ILD) explicitly address progression despite first-line treatment 1. When ILD progresses on current therapy, the recommendation is to add or switch to other agents—not to discontinue existing immunosuppression. The guideline conditionally recommends mycophenolate, rituximab, cyclophosphamide, and nintedanib as treatment options for SARD-ILD progression 1.

Key Management Principles:

For IIM-ILD exacerbation (non-rapidly progressive):

• Continue mycophenolate as baseline therapy
• Add rituximab (preferred addition for IIM-ILD per guideline) 1
• Alternative additions: cyclophosphamide, nintedanib, or calcineurin inhibitors (tacrolimus)
• Short-term glucocorticoids may serve as a bridge but should not be relied upon long-term (>3-6 months) 1

For rapidly progressive ILD (RP-ILD): If this is truly RP-ILD (life-threatening, rapid deterioration), the approach changes dramatically:

• Initiate upfront combination therapy immediately 1
• Pulse IV methylprednisolone plus 2-3 agents from: rituximab, cyclophosphamide, IVIG, tacrolimus, mycophenolate, or JAK inhibitor 1
• The guideline conditionally recommends JAK inhibitors as first-line treatment for IIM-ILD 1, making continuation of your JAK inhibitor (Jascayd/upadacitinib) appropriate
• Rituximab and cyclophosphamide are preferred over JAK inhibitors in RP-ILD, but JAK inhibitors remain viable options 1

Specific Medication Considerations

Mycophenolate:

• Effective in IIM-ILD with evidence of FVC stabilization/improvement 2, 3, 4
• The FDA label warns about infection risk and neutropenia but does not contraindicate use during disease flares 5
• Discontinuation would eliminate a proven disease-modifying agent

JAK Inhibitor (Jascayd/Upadacitinib):

• The 2023 ACR/CHEST guideline conditionally recommends JAK inhibitors as first-line ILD treatment for IIM-ILD 1
• Observational data suggest effectiveness in MDA-5-ILD and potential benefit when added to other therapy in refractory cases 1
• While cyclophosphamide, rituximab, and mycophenolate are preferred over JAK inhibitors in RP-ILD, JAK inhibitors remain recommended treatment options 1

Critical Pitfalls to Avoid

1. Do not withdraw immunosuppression during active disease exacerbation unless there is overwhelming infection or other absolute contraindication
2. Do not rely on glucocorticoids alone for progressive ILD—they have a bridging role only 1
3. Distinguish between chronic progressive ILD and RP-ILD, as treatment intensity differs markedly
4. Monitor for infection risk when intensifying therapy, but this is managed through surveillance, not by stopping effective agents 5

Recommended Action Algorithm

1. Assess severity: Is this chronic progressive ILD or life-threatening RP-ILD?
2. Continue mycophenolate and JAK inhibitor as baseline therapy
3. Add rituximab (1000 mg IV on day 1 and day 15) as the preferred escalation for IIM-ILD 1, 6
4. Consider pulse IV methylprednisolone (500-1000 mg daily × 3 days) as a bridge if severe
5. If RP-ILD: Escalate to triple therapy (glucocorticoids + rituximab + cyclophosphamide or tacrolimus) while continuing JAK inhibitor 1
6. Monitor closely: CBC weekly initially, infection surveillance, pulmonary function tests 5

The evidence strongly supports intensification rather than withdrawal of immunosuppression during ILD exacerbation in polymyositis.