ORIGINAL ARTICLES
Efficacy and safety of roflumilast in the treatment of asthma

https://doi.org/10.1016/S1081-1206(10)61065-4Get rights and content

Background

The central role of chronic inflammation of the airways in asthma pathogenesis is supported by the efficacy of corticosteroids in controlling clinical symptoms. However, the search continues for potentially safer anti-inflammatory alternatives. Roflumilast is an oral, once-daily phosphodiesterase type 4 inhibitor with anti-inflammatory activity in preclinical models of asthma and chronic obstructive pulmonary disease.

Objective

To investigate the dose-ranging efficacy and safety of roflumilast in patients with mild-to-moderate asthma.

Methods

Patients (N = 693) were randomized in a double-blind, parallel-group, phase 2/3 study. After a 1- to 3-week placebo run-in period, patients (mean forced expiratory volume in 1 second [FEV1], 73% of predicted) were randomized to receive 100, 250, or 500 μg of roflumilast once daily for 12 weeks. The primary end point was change from baseline in FEV1; secondary end points included change from baseline in morning and evening peak expiratory flow.

Results

Roflumilast use significantly increased FEV1 (P < .001 vs baseline). Improvements from baseline in FEV1 at the last visit were 260, 320, and 400 mL for the 100-, 250-, and 500-μg dose groups, respectively. Roflumilast, 500 μg, was superior to roflumilast, 100 μg, by 140 mL in improving FEV1 (P = .002). There were also significant improvements from baseline in morning and evening peak expiratory flow in all the dose groups (P ≤ .006). Roflumilast was well tolerated at all doses tested. Most adverse events were mild to moderate in intensity and transient.

Conclusion

These results support the emerging role of roflumilast, 500 μg/d, in the treatment of asthma.

REFERENCES (31)

  • AM Vignola

    Effects of inhaled corticosteroids, leukotriene receptor antagonists, or both, plus long-acting β2-agonists on asthma pathophysiology: a review of the evidence

    Drugs

    (2003)
  • HR Bourne et al.

    Modulation of inflammation and immunity by cyclic AMP

    Science

    (1974)
  • JA Beavo

    Cyclic nucleotide phosphodiesterases: functional implications of multiple isoforms

    Physiol Rev

    (1995)
  • SH Francis et al.

    Cyclic nucleotide phosphodiesterases: relating structure and function

    Prog Nucleic Acid Res Mol Biol

    (2001)
  • TJ Torphy

    Phosphodiesterase isozymes: molecular targets for novel antiasthma agents

    Am J Respir Crit Care Med

    (1998)
  • Cited by (84)

    • Roflumilast for asthma: Efficacy findings in non-placebo-controlled comparator and dosing studies

      2015, Pulmonary Pharmacology and Therapeutics
      Citation Excerpt :

      Since asthma is a heterogeneous disease it is not surprising that anti-inflammatory treatments with different mechanisms of action are beneficial both as monotherapy and when combined, and the search for additional options has resulted in the development of a variety of classes of treatment, including phosphodiesterase-4 inhibitors [4,5], monoclonal antibodies, IgE, and other inflammatory targets [5]. As described in companion papers in this edition of the journal (Meltzer et al., Placebo-controlled studies and Bardin et al., Mechanism of Action studies), the pharmacology and mechanism of action of the oral phosphodiesterase-4 inhibitor roflumilast and its confirmed role in the management of COPD (it is approved in patients with severe COPD associated with chronic bronchitis and a history of exacerbations), support a potential role for it in the treatment of asthma [6,7]. The indication in severe chronic obstructive pulmonary disease (COPD) is as an add-on treatment for patients with symptoms of chronic bronchitis and a history of frequent exacerbations.

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    This study was sponsored by ALTANA Pharma AG, Konstanz.

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