Novel TherapyThe goal of asthma management is to achieve and maintain control of the disease while minimizing the occurrence or severity of adverse drug events (ADEs) from the therapies used. We know from multiple, large, community-based studies that despite the promulgation of an international effort and guidelines to standardize the assessment and management of asthma, most asthma patients continue to experience a high rate of symptoms and functional impairment from their ill-ness.

Strategies to improve asthma control can lead to socioeconomic gains in terms of improved school attendance; fewer absences from work; and, by implication, a smaller burden on families.

Most clinical studies of asthma therapies focus on the incremental improvements in individual endpoints obtained with fixed doses of medication. Although these studies are helpful in assessing an incremental benefit of a particular medication, they usually do not compare how groups of medications work together as a regimen. Consensus treatment guidelines—reference tools frequently used by practicing physicians—must rely on the results of these individual efficacy trials, combined with the consensus judgment of expert panels. As consensus documents based on individual drug trials, consensus treatment guidelines in their totality—such as the Global Initiative for Asthma/National Institutes of Health (GINA/NIH) guidelines—are rarely themselves subject to rigorous scientific validation (e.g., patient outcomes using guideline care versus baseline care).

The Gaining Optimal Asthma controL (GOAL) study addressed the issue of efficacy of the asthma treatment guidelines, subjecting more than 3,000 patients with documented, suboptimally controlled asthma to rigorous adherence with predefined, stepwise increases in either drug salmeterol/canadian fluticasone, or fluticasone propionate (e.g., Flonase, Flovent, GlaxoSmith-Kline). Under the study protocols, dosage acceleration continued until the patients reached a defined state of asthma control or the maximum dose of medication. For patients receiving salmeterol/fluticasone, 41% achieved total control of their asthma and 71% achieved good control. Both of these values were significantly higher, compared with the baseline of 28% and 59%, respectively, prior to guideline-directed dose escalation.

The authors concluded that for most asthma patients, comprehensive guideline-defined control can be achieved and maintained. On the basis of this study, they further suggested that total control should be the aim of treatment for all patients with asthma. This aggressive approach runs counter to a conventional belief held by many experts—that full control of asthma is an unrealistic goal for most of these patients. Factors promoting these conventional beliefs include limitations of current treatments, problems with treatment strategies, lowered physician and patient expectations regarding outcomes, and concerns about adherence to treatment.

The GOAL study results generate several interesting questions for the future of asthma treatment guidelines:

1.  Should total control of symptoms be the target for all asthmatic patients, regardless of the initial severity of disease?

2.  If total control is a realistic goal for many patients, are the current asthma treatment recommendations adequate to meet this challenge? Considering that more than 30% of patients did not achieve a well-controlled state despite systematic and rigorous adherence to current guidelines, what other modalities should be factored into the equation to increase the percentage of patients achieving control?

There are clearly limits to the efficacy of standard asthma therapy. As a result of the GOAL study, many patients continued taking higher doses of inhaled fluticasone (1,000 mcg/day) without achieving the level of symptom control sought by the researchers. The maximum effect of inhaled corticosteroids is typically reached at doses in the low-to-medium range. Higher doses do not typically improve efficacy measures but do have an impact on systemic effect measures, causing a plateau effect.

In addition, the use of high doses of fluticasone over prolonged periods presents an unknown risk. The GOAL results suggest an algorithm in which omalizumab is prescribed when patients do not respond adequately to salmeterol/fluticasone 50/500 mcg twice daily—an approach that may increase the probability of reaching GOAL endpoints without using high-dose steroids over prolonged periods.

As a nontraditional agent targeting IgE-mediated allergic asthma, omalizumab is a strong candidate to fill the void between maximal standard therapy and total control. In the INNOVATE trial, omalizumab was tested in a subpopulation of severe-persistent asthmatic patients who had not achieved adequate control despite maximal standard treatment (GINA step 4).

As an add-on therapy in this challenging population, omal-izumab significantly reduced the rate of severe asthma exacerbations by 50%, reduced emergency department visits by 44%, and improved asthma-related quality of life. These improvements occurred without an increase in overall ADEs, a burdensome aspect of step 4 treatment, and any ADEs were generally well tolerated.

It was the large numbers of patients with inadequately controlled symptoms, despite maximum conventional therapy, coupled with the belief that total or adequate control is an attainable goal for most asthma patients, that prompted the Asthma Consensus Panels I and II to recommend consideration of omalizumab as an add-on medication to maximal standard therapy in patients with moderate-persistent to severe-persistent asthma.

Conclusion

The growing awareness of the limitations of standard therapy is one of the most compelling reasons for pursuing the development of new modalities to treat the underlying causes of asthma.

A plateau effect has been observed in the dose-response curve of inhaled corticosteroids, whereby increasing the dose increases only the systemic effects but not physiological improvement. With the FDA’s approval of omalizumab, a panel of experts in the fields of allergy and pulmonology proposed additions to the NAEPP clinical guidelines and recommended that IgE blockers be used as an alternative treatment in patients with moderate-persistent to severe-persistent asthma whose disease is suboptimally controlled with high-dose inhaled corticosteroids or in patients who need systemic corticosteroids. canadian pharmacy viagra

IgE blockers can also be considered in patients whose asthma is inadequately controlled despite a three-month trial of medium-dose inhaled corticosteroids and long-acting beta agonists or leukotriene receptor agonists. The panel also advised that specific patient education recommendations be added to the guidelines for all levels of severity.

Although a cure for asthma has not yet been discovered, novel treatment modalities, such as IgE blockers, represent a new and unique opportunity for improved control in many asthma patients. Predicting the response of patients with severe, intensely treated asthma to omalizumab will be an important issue for future study.
With the advent of new technologies and treatment modalities, many asthma experts now believe that total control is a realistic goal that can and should be achieved and maintained for the majority of patients with asthma.

Category: Diseases / Tags: National Guidelines, Novel Therapy

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