Tofacitinib Dosing for Myositis-Associated Interstitial Lung Disease
For anti-MDA5 antibody-positive dermatomyositis with interstitial lung disease, initiate tofacitinib at 5 mg orally twice daily (10 mg/day total) as add-on therapy to triple immunosuppression (high-dose glucocorticoids, cyclophosphamide, and tacrolimus), with dose escalation to 10 mg twice daily (20 mg/day total) reserved for refractory cases despite initial therapy. 1, 2
Standard Initial Dosing Protocol
Start with 5 mg orally twice daily (10 mg/day total) when adding tofacitinib to triple therapy (high-dose glucocorticoids, cyclophosphamide, and calcineurin inhibitor like tacrolimus) for anti-MDA5-positive dermatomyositis with rapidly progressive ILD 1, 2, 3
The 11 mg extended-release formulation once daily can be used as an alternative to immediate-release 5 mg twice daily for patient convenience, particularly in early-stage ILD 4
Initiate tofacitinib approximately 4 weeks after starting pulse corticosteroid treatment in early-stage ILD cases 4
Dose Escalation for Refractory Disease
Escalate to 10 mg orally twice daily (20 mg/day total) only when patients show poor response to the standard 10 mg/day dose combined with triple immunosuppression 1, 2
In a case series of six refractory MDA5-DM patients, dose escalation from 10 mg to 20 mg/day resulted in improvement in four patients (67%), though two non-responders died 1
One case report demonstrated marked response after increasing from 10 mg/day to 20 mg/day in a patient who had failed triple therapy plus standard-dose tofacitinib 2
Critical Pre-Treatment Requirements
Complete tuberculosis screening with interferon-gamma release assay (IGRA) or tuberculin skin test before initiation, with treatment of latent TB for at least 1 month prior to starting tofacitinib 5
Administer recombinant zoster vaccine (Shingrix) as a 2-dose series separated by 2-6 months before starting therapy in patients ≥18 years old 5
Obtain baseline complete blood count with differential, comprehensive metabolic panel including liver enzymes and renal function, and lipid profile 5
Do not initiate if lymphocyte count, absolute neutrophil count, or hemoglobin are below safe thresholds 6, 5
Infection Risk Management
All six patients (100%) in the dose-escalation case series developed at least one infection, including five cases of cytomegalovirus reactivation, one pulmonary aspergillosis, one herpes zoster, and one herpes simplex keratitis 1
The high infection rate necessitates aggressive monitoring for opportunistic infections, particularly CMV reactivation, when using tofacitinib at any dose for myositis-ILD 1
Avoid initiating or continuing tofacitinib during any active serious infection 6, 5
Monitoring Schedule During Treatment
Repeat CBC with differential at 4-8 weeks after starting treatment, then every 3 months 5, 7
Check liver enzymes at 4 weeks, then every 3 months as part of comprehensive metabolic panel 5, 7
Measure lipids at 4-12 weeks after initiation, then annually 5, 7
Monitor for signs of infection continuously, with low threshold for CMV PCR testing given the extremely high reactivation rate in myositis-ILD patients 1
Dose Modifications for Specific Situations
Reduce to 5 mg once daily in patients with moderate to severe renal or hepatic impairment 6
Use 5 mg once daily when combining with potent CYP3A4 inhibitors (e.g., ketoconazole) or medications causing both moderate CYP3A4 inhibition and potent CYP2C19 inhibition (e.g., fluconazole) 6
Hold tofacitinib until hemoglobin values normalize if anemia develops during treatment 6
Important Caveats
There are no FDA-approved indications for tofacitinib in myositis or myositis-associated ILD; all use is off-label based on case series and case reports 1, 2, 3, 4
The evidence base consists entirely of observational data from Japanese populations with anti-MDA5-positive disease, limiting generalizability 1, 2, 3, 4
The risk-benefit balance of dose escalation to 20 mg/day must be carefully assessed in each case, given the 100% infection rate and 33% mortality in the dose-escalation cohort 1
Do not combine tofacitinib with other potent immunosuppressants beyond the established triple therapy regimen, and avoid combination with biologics 6
Patients ≥65 years have significantly higher serious infection rates and should only receive tofacitinib if no alternative exists 5