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A disease looking for innovative drugs: The case of pulmonary arterial hypertension

      Highlights

      • Treatments for PAH approved in EU are not disease-modifying therapies.
      • Compared to placebo treatments for PAH as a whole reduce mortality.
      • No specific drug or class of medicines but prostanoids proved effective in itself.
      • Combinations provide no longer survival than monotherapies.
      • Drug approvals in spite of poor evidence can harm patient and hamper further R&D.

      Abstract

      Background

      Pulmonary arterial hypertension (PAH) is a life-threatening rare disease. Between 2001 and 2016 the European Medicines Agency (EMA) approved nine drugs to treat PAH. Considering the poor prognosis of patients with PAH it would be useful to understand whether the approved therapies can change the natural history of the disease. We assessed the therapeutic value and the quality of the evidence on medicines that have been authorized by the EMA in the 2000s.

      Methods

      Information about drug approval was obtained from the EMA website and the European Public Assessment Reports. MedLine, Embase, and Cochrane databases were systematically searched for published randomized clinical trials and meta-analyses of the selected drugs and their combinations.

      Results

      At the time of approval no medicine had been proved to reduce mortality or slow the progression of the disease or to improve patients' quality of life. Recent meta-analyses concluded that, compared to placebo, active treatments reduced mortality but there was no conclusion on any preferred therapeutic option. Approvals of monotherapies in the absence of best evidence of their efficacy, have prompted the search for better efficacy of their combinations. Three meta-analyses found no advantage in survival from combinations as opposed to monotherapies.

      Conclusions

      This model case confirms previous analyses that marketing authorizations granted in spite of low evidence of therapeutic efficacy not only expose patients to treatments with unknown benefit-risk profiles but also hamper post-marketing research aimed at filling the information gap.

      Keywords

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