ALTERNATIVE ANTI-INFLAMMATORY AND IMMUNOMODULATOR MEDICATIONS FOR ASTHMA

Abstract

The National Institutes of Health (NIH) 1997 Expert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma 12 (EPR2) proposes a standard of care for patients with this chronic, predominantly eosinophilic, inflammatory disease: that patients with mild persistent asthma be treated with daily low-dose inhaled corticosteroids, that patients with moderate persistent asthma receive higher doses of inhaled corticosteroids, and that patients with severe persistent asthma be treated with the highest doses of inhaled corticosteroids, long-acting bronchodilators, and the lowest doses of oral corticosteroids that can achieve the therapeutic goal. The EPR2 suggests other medications as add-on therapy or as alternatives. This article reviews randomized clinical trials that address alternative medications for the management of persistent asthma in patients who require daily treatment. When available, head-to-head comparisons are discussed. Traditionally, alternative anti-inflammatory treatments for asthma are given to patients with severe disease that requires higher doses of oral corticosteroids for control of symptoms. The experience of rheumatologists treating patients with arthritis has led to the suggestion that methotrexate, gold salts, hydroxychloroquine, dapsone, and cyclosporin may be of benefit for severe steroid-dependent asthmatic patients. In contrast, for patients with mild to moderate persistent asthma, alternative medications with potential anti-inflammatory effect include cromolyn sodium, nedocromil, theophylline, and the leukotriene modifiers. Several of these agents, as well as long acting oral and inhaled bronchodilators, have also been proposed as effective means to reduce the daily dose of the inhaled corticosteroid while maintaining or improving control of asthma. Outcome parameters vary among studies. The most common objective measures include forced expiratory volume in 1 second (FEV 1 ), peak expiratory flow rate (PEFR), and measures of bronchial hyperreactivity. Dosage levels of oral corticosteroids taken for asthma, albuterol use, and level of symptom control are also reported indicators of efficacy. The adverse drug profile of each therapy needs to be considered. Most clinical studies unfortunately are short-term, and many of the potential safety concerns may appear only after several years of treatment. Study populations, even when controlled for disease severity, differ among clinical investigations and make comparative analysis difficult. Randomized clinical trials of two or more therapies provide the best comparisons. In analyzing the outcomes of alternative medications, one needs to consider the placebo effect on clinical changes. Many clinical trials have demonstrated that enrollment alone can improve lung function and symptom control. In placebo-controlled trials, a clinically significant difference, not just a statistical difference, needs to be demonstrated.