Can tofacitinib (Xeljanz) be given to a patient with Hypertrophic Obstructive Cardiomyopathy (HOCM)?

Can Tofacitinib Be Given in HOCM?

Tofacitinib can be used in patients with HOCM, but requires careful monitoring for hemodynamic effects and should be avoided if the patient has symptomatic obstructive physiology with high resting gradients or is hemodynamically unstable.

Key Pharmacologic Considerations

The primary concern with tofacitinib in HOCM relates to its potential cardiovascular effects rather than a direct contraindication. The critical issue is whether tofacitinib causes vasodilation or affects cardiac contractility, which could worsen left ventricular outflow tract (LVOT) obstruction.

Medications That Worsen HOCM

According to ACC/AHA guidelines, the following medication classes are problematic in HOCM:

• Pure vasodilators (ACE inhibitors, ARBs, dihydropyridine calcium channel blockers) can worsen LVOT obstruction and are relatively contraindicated in symptomatic obstructive HCM 1
• High-dose diuretics should be avoided as volume depletion worsens dynamic obstruction 1, 2
• Positive inotropic agents (like digoxin) are potentially harmful in patients without atrial fibrillation 3, 2

Tofacitinib's Cardiovascular Profile

Tofacitinib is a JAK inhibitor used primarily for rheumatoid arthritis and inflammatory bowel disease. It does not function as a vasodilator, positive inotrope, or diuretic—the medication classes specifically cautioned against in HOCM guidelines 1.

Clinical Decision Algorithm

For Asymptomatic HOCM Patients:

• Tofacitinib can be used with standard monitoring 1
• Ensure adequate hydration and avoid situations promoting vasodilation 1

For Symptomatic HOCM Patients:

• Assess resting LVOT gradient and symptom severity first
• If gradient <50 mm Hg and well-controlled on beta-blockers or verapamil: tofacitinib is reasonable with close monitoring 1, 3
• If gradient ≥80-100 mm Hg with heart failure signs: use extreme caution and consider alternative immunosuppressive therapy 1

For Patients on HOCM-Specific Therapy:

• Continue beta-blockers or verapamil as first-line therapy 3, 2
• Monitor for any new symptoms after initiating tofacitinib that could indicate worsening obstruction 1
• If symptoms emerge after starting tofacitinib, reassess treatment strategy and consider up-titrating HOCM medications 1

Critical Monitoring Parameters

When using tofacitinib in HOCM patients, monitor for:

• Hemodynamic stability: Watch for hypotension or orthostatic symptoms that could worsen LVOT obstruction 1
• Volume status: Maintain euvolemia, as both dehydration and fluid overload are problematic 2
• New or worsening symptoms: Dyspnea, chest pain, lightheadedness, or syncope may indicate worsening obstruction 1

Important Caveats

The ACC/AHA guidelines emphasize that caution should be exercised when introducing therapies for coexisting conditions in HCM patients 1. While tofacitinib is not specifically mentioned in HOCM guidelines (as it's not a cardiovascular medication), the general principle is that medications can be used in asymptomatic patients, but if symptoms are present or emerge after initiation, treatment strategy reassessment is necessary 1.

The absence of tofacitinib from the list of contraindicated medications in comprehensive HOCM guidelines 1, 3, 2 suggests it does not share the problematic mechanisms (vasodilation, positive inotropy, volume depletion) that worsen LVOT obstruction.

Aggressive treatment of comorbid conditions contributing to cardiovascular disease should proceed in compliance with existing guidelines, as recommended by the ACC/AHA 4. This supports using necessary immunosuppressive therapy like tofacitinib when clinically indicated, with appropriate monitoring for any adverse hemodynamic effects specific to the patient's HOCM severity.