Mixed Connective-Tissue Disease Medication

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Class Summary

These agents reduce pain and inflammation and allow for improvement in mobility and function. Mild mixed connective-tissue disease (MCTD) may be controlled with NSAIDs. Arthritis/arthralgia can often be controlled with NSAIDs and hydroxychloroquine. Low-dose oral corticosteroids or low-dose methotrexate is reserved for more refractory synovitis.

Naproxen (Naprosyn, Naprelan, Aleve, Anaprox)

Used to treat musculoskeletal manifestation of MCTD, including arthralgia and arthritis. Inhibits inflammatory reactions and pain by decreasing enzyme COX activity, which results in prostaglandin synthesis.

Class Summary

Although increased cost can be a negative factor, COX-2 inhibitors may be more effective in reducing the incidence of costly and potentially fatal GI bleeding than traditional NSAIDs. COX-2 inhibitors and many traditional NSAIDs may increase the risk of atherosclerotic cardiovascular endpoints.

Celecoxib (Celebrex)

Used to treat musculoskeletal manifestations of MCTD, including arthralgia and arthritis. Inhibits primarily COX-2, which is considered an inducible isoenzyme (ie, induced during pain and inflammatory stimuli).

Inhibition of COX-1 may contribute to NSAID GI toxicity. At therapeutic concentrations, COX-1 isoenzyme is not inhibited; thus, GI toxicity may be decreased. Seek lowest dose of celecoxib for each patient.

Class Summary

Esophageal reflux symptoms can be controlled effectively with these agents.

Omeprazole (Prilosec)

Inhibits gastric acid secretion by inhibition of the H⁺/K⁺ -ATPase enzyme system in gastric parietal cells. May be effective to treat reflux symptoms in MCTD.

Class Summary

Mild MCTD can often be controlled with hydroxychloroquine. Hydroxychloroquine may also help prevent disease flares.

Hydroxychloroquine (Plaquenil)

Inhibits chemotaxis of eosinophils, locomotion of neutrophils, and impairs complement-dependent antigen-antibody reactions.

Hydroxychloroquine sulfate 200 mg is equivalent to 155 mg hydroxychloroquine base and 250 mg chloroquine phosphate.

Class Summary

These agents are reserved for more active or severe disease. They are used in moderate-to-high doses for major organ involvement. They are often used in combination with other drugs.

Prednisone (Deltasone, Orasone, Meticorten)

Used for its anti-inflammatory and immunomodulatory effects.

May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.

Class Summary

Avoiding exposure to cold temperatures and using long-acting calcium channel blocking agents may control Raynaud phenomenon. Calcium channel blocking agents are used for vasodilation and possible antiplatelet effects.

Nifedipine (Adalat, Procardia XL)

Used to treat Raynaud phenomenon in MCTD. Causes vasodilation in extremities.

Class Summary

Phosphodiesterase inhibitors can ameliorate symptoms of pulmonary hypertension and Raynaud phenomenon in patients with MCTD. These agents may not be as durable as other drug classes in improving pulmonary hypertension, but the adverse-effect profile of phosphodiesterase inhibitors is often more favorable than prostaglandin or anti-endothelin therapies.

Sildenafil

Promotes selective smooth-muscle relaxation in lung vasculature, possibly by inhibiting phosphodiesterase type 5 (PDE-5). This reduces blood pressure in pulmonary arteries and increase in cardiac output.

Class Summary

These agents may be helpful for managing pulmonary hypertension in patients with MCTD. The risk of liver toxicity with endothelin receptor antagonists dictates that these drugs must be prescribed by experts.

Ambrisentan

Endothelin receptor antagonist indicated for pulmonary arterial hypertension in patients with WHO class II or III symptoms. Improves exercise ability and decreases progression of clinical symptoms. Inhibits vessel constriction and elevation of blood pressure by competitively binding to endothelin-1 receptors ET_A and ET_B in endothelium and vascular smooth muscle. This leads to significant increase in cardiac index associated with significant reduction in pulmonary artery pressure, pulmonary vascular resistance, and mean right atrial pressure. Because of the risks of hepatic injury and teratogenic potential, only available through the Letairis Education and Access Program (LEAP). Prescribers and pharmacies must register with LEAP in order to prescribe and dispense. For more information, see http://www.letairis.com or call (866) 664-LEAP (5327).

Class Summary

These agents may be useful for managing pulmonary hypertension in patients with MCTD, although dose titration and administration should be managed by an expert in this drug.

Epoprostenol (Flolan)

Strong vasodilator of all vascular beds. May decrease thrombogenesis and platelet clumping in the lungs by inhibiting platelet aggregation.

Class Summary

Major organ involvement may require moderate-to-high divided daily doses of corticosteroids and cytotoxic agents (eg, PO or pulse IV cyclophosphamide). Recent reports suggest that, in contrast to primary or scleroderma-associated pulmonary hypertension, a subset of MCTD patients with pulmonary hypertension may respond well to aggressive immunosuppression with cytotoxic agents.

Cyclophosphamide (Cytoxan)

Chemically related to nitrogen mustards. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells.

Administered as monthly IV infusion or, less commonly, as daily PO medication for severe MCTD.