Progress in practice: ADKA Congress

Examples of rare diseases include neuronal ceroid lipofuscinosis, spinal muscular atrophy and systemic lupus erythematosus.

Typical problems encountered by patients with rare diseases include a long time before diagnosis, lack of understanding of the disease by healthcare professionals, friends and family, the search for competent disease management and the absence of therapeutic options. Another problem is that many adult patients are treated in paediatric clinics because there is no effective mechanism for transfer to adult clinics, said Dr Reimann.

The results of a recent survey of patient preferences showed an almost universal wish for more information about treatment options and for consistency of care (seeing the same doctor regularly). In addition, 64% of patients would like to be treated near to their homes, emphasised Dr Reimann.

Medicines are just part of a management scheme that could also include, for example, surgery, physiotherapy and dietetic advice. Furthermore, many of the medicines are used on an off-label or ‘compassionate use’ basis. Orphan drug designation, which compensates a manufacturer for low usage by giving ten-year market exclusivity (after a marketing authorisation has been granted), has been helpful for some products. An example is ivacaftor (Kalydeco®, Vertex), which has orphan drug status in the USA. A decision on marketing approval in Europe is expected in August 2012. Ivacaftor is a small-molecule potentiator of the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel. The effect is to improve chloride transport at the cell surface and thereby reverse some of the features of cystic fibrosis.

In addition, Dr Reimann said that hospital pharmacists should manage the medicines at the time of discharge and ensure that specialist nurses and community pharmacists are fully briefed about the supply and use of specialist medicines. He emphasised that “communication about medicines is communication about risks”. When asked in a major survey if they had been made aware of medicines’ side-effects that they should look out for, 50% of patients replied either ‘now and again’ or ‘never’. This is a topic to which pharmacists should pay special attention, he suggested.

In conclusion, Dr Reimann called for close cooperation between community and hospital pharmacists to support patients with rare diseases.

During the discussion, Irene Kraemer (Director of Pharmacy, University Hospital Mainz, President ADKA) said that another important role of the pharmacist was in research, for example, concerning the formulation and use of nebulised medicines for patients with CF.

In future, pharmacists will be the repository of specialist knowledge about genetic variations in drug handling, Theodor Dingerman (Professor of pharmaceutical biology, Goethe University, Frankfurt, Germany) told the audience. The current paradigm for evidence-based medicine relies on the double-blind clinical trial to separate responders to a given treatment from non-responders. However, a new paradigm based on molecular diagnostic techniques would allow identification of non-responders, partial responders and responders. This would allow prediction of those patients in whom a drug would work and those who would be unable to tolerate a drug, and lead to the development of ‘stratified pharmacotherapy’ he explained.

The first phase of drug metabolism involves enzymes of the cytochrome p450 family (CYPs), esterases, hydrolases and other enzymes, many of which are subject to polymorphism. For example, numerous drugs, including antidepressants, anti-arrhythmics, neuropletics and many others, are substrates for CYP2D6, which can exist in a number of genetically determined forms. Once this information is known, problems can be anticipated and doses can be adjusted according to genotype.

For some drugs there are large differences; for example, poor metabolisers of imipramine require about 25% of a standard dose whereas ultra-rapid metabolisers require more than 150% of the normal dose. In contrast, the differences are much less marked with other drugs, such as clozapine. Another example is polymorphisms of the gene SLCO1B1, which codes for an anion transporter protein in the liver. Common variants in SLCO1B1 are linked to higher risks of statin-induced mypopathy. These variations have a significant effect on simvastatin (requiring dose reduction) but little effect on fluvastatin, said Professor Dingerman.

In conclusion, he said that the evidence for genetic variations in drug handling is at least as good as that for clinically relevant drug interactions. What is needed now is more awareness building because this is definitely not a niche problem.

In a session devoted to brief reviews of ‘top papers’ – landmark publications of which clinical pharmacists should be aware – Martin Hug (Director of Pharmacy, University Hospital Freiburg, Germany) described how the first study of a myosin-activator, omecamtiv mecarbil, had shown that the drug increased left ventricular ejection time and stroke volume whilst decreasing left ventricular end diastolic volume. It is as yet unknown what effect this drug will have on the overall clinical outcome for heart failure patients, noted Dr Hug.

The SU.FOL.OM3 study related to the effects of B-vitamins and fish oil. Patients with a history of ischaemic heart disease or stroke were randomised to receive B-vitamins or fish oil supplements, or both or placebo. After a five-year follow-up, neither B-vitamins nor fish oils had any effect on cardiovascular endpoints (myocardial infarction, stroke or cardiovascular death). However, there was a significantly increased risk of cancer in female patients.

Bacteria collected from an isolated cave microbiome turned out to be resistant to a large number of modern antibiotics, according to a study reviewed by Matthias Fellhauer (Director of Pharmacy, Schwarzwald-Baar Hospital, Villingen-Schwenningen, Germany). The Lechuguilla cave complex in New Mexico has been isolated for at least four million years and human access to the caves has been strictly controlled in recent years. In this study, bacteria collected from the caves and cultured showed resistance to a range of structurally different antibiotics including aminoglycosides, macrolides, penicillins, sulphamethoxazole and trimethoprim. The list also included daptomycin, an antibiotic of last resort in the treatment of drug-resistant Gram-positive pathogens. This suggests that resistance genes are ‘old’ and natural and not the result of recent exposure to antibiotics – the use of antibiotics simply uncovers existing resistance mechanisms, explained Dr Fellhauer. It is possible that these mechanisms have some other purpose and might confer some evolutionary advantage. It is also possible that they are result of exposure to naturally occurring antibiotics in the environment that are yet to be discovered, he added.