Issue one of the second volume of Therapeutics and Clinical Risk Management presents
a range of review articles from internationally recognised authors, each of whom addresses
an important and apposite topic in the therapeutic management of clinical risk.
Overactive bladder (OAB) and urinary incontinence are prevalent and distressing conditions
with significant associated direct and indirect economic costs. Moreover, the majority
of OAB patients do not present for treatment in spite of a considerable reduction
in mental health and health-related quality of life. Antimuscarinic agents have been
at the forefront of therapy for OAB for 30 years; however, patient compliance rates
are extremely poor as a result of drug expenses, suboptimal dosage regimens, a commonly
incomplete improvement in symptoms, and intolerable systemic side-effects. McCrery
and Appell review the latest alternative drug delivery systems for the antimuscarinic
agent, oxybutynin chloride (OXY), including OXYER, an extended-release formulation,
and OXY-TDS, a transdermal system, together with a range of other antimuscarinic agents.
The worldwide prevalence of asthma has increased to approximately 300 million and
represents a major socioeconomic and healthcare load. The established efficacy of
inhaled corticosteroids (ICS) has resulted in their being promoted as the cornerstone
of asthma therapy. However, local and systemic adverse effects can limit their use
and result in significantly reduced compliance. Ronald Dahl presents a comprehensive
review of ciclesonide, a nonhalogenated corticosteroid that demonstrates potent anti-inflammatory
activity with similar efficacy to other ICS in asthma and did not elicit unfavorable
side effects at dosages used in clinical trials. This knowledge may enhance the management
of this prevalent condition in which poor compliance to prescribed medication is common.
The number of liver transplants secondary to hepatitis viruses has risen substantially
over the past 20 years in Europe and the US. Approximately 50% are due to infection
with hepatitis C virus (HCV) and projections suggest that the impact on public health
will continue to increase. Picciotto reviews the natural history of HCV patients following
transplant and the available therapeutic options, for which there is as yet no consensus.
Post-transplant clinical sequelae are characterized in most patients by HCV reinfection
and development of chronic hepatitis. Therapeutic strategies for the management of
HCV during the peri-transplant phase include pretransplant prophylaxis to prevent
the transplanted organ becoming infected; post-transplant prophylaxis to attenuate
risk of acute hepatitis; and management of the stablized chronic disease state.
Musculoskeletal conditions, including rheumatoid arthritis (RA) and osteoarthritis
(OA) amongst others, represent a significant burden in terms of socioeconomic cost
and morbidity. Although nonsteroidal antiinflammatory drugs (NSAIDs) play an important
role in the management of RA and OA, their longer-term use is associated with considerable
upper gastrointestinal symptoms that contribute to poor compliance and inadequate
control of inflammation and pain. Etoricoxib is a selective COX-2 inhibitor, a subclass
of NSAIDs that demonstrate comparable clinical efficacy to traditional NSAIDs together
with significantly reduced gastrointestinal toxicity. The timely evaluation from Brooks
and Kubler reviews the pharmacology of etoricoxib and summarizes the current clinical
data on its efficacy, tolerability, and patient acceptability.
Zhanel and colleagues examine the role of telithromycin, the first ketolide antibiotic
to gain US Food and Drug Administration (FDA)-approval for the treatment of acute
bacterial sinusitis, acute exacerbations of chronic bronchitis, and community-acquired
pneumonia in adult outpatients. Collectively, these three conditions are responsible
for significant morbidity and substantial socioeconomic costs. The authors present
a review of the mechanisms by which telithromycin exerts its antibacterial activity
and also assess the pharmacokinetic and pharmacodynamic properties, clinical efficacy,
and tolerability-safety profiles.
The increasing prevalence of osteoporosis worldwide contributes significantly to morbidity
and mortality amongst our aging populations with considerable attendant health and
financial implications. In the first of two complementary reviews examining the primary
role of the bisphosphonates in the management of osteoporosis, Bauss and Schimmer
comprehensively review the efficacy and safety of ibandronate, a highly potent N-containing
bisphosphonate that combines the known efficacy of this drug class with enhanced safety
and tolerability profiles. Grey and Reid use the limited available data to critically
evaluate the differences between agents of this expanding class of drugs in terms
of potency, administration route, duration of action, and efficacy. Bisphosphonates
demonstrate a high antiresorptive potency that allows lower doses and extended dosing
intervals and has recently been approved as the first once-monthly oral drug for the
treatment and prevention of postmenopausal osteoporosis in the US.
Larkin and Eisen report that incidence of renal cell carcinoma (RCC) in the UK increased
by almost 20% between 1991 and 2000. In cases of metastatic RCC, whilst immunotherapy
may offer a small overall increase in survival, it does not benefit the majority of
patients and there is thus a need to elucidate new therapeutic approaches. Sorafenib
is an orally administered, novel member of the kinase inhibitor class of drugs. In
phase 2 studies amongst patients with RCC pretreated with immunotherapy, it has demonstrated
significant activity with manageable toxicity while a phase 3 study has shown prolonged
progression-free survival when compared with placebo.
In the second of our two complementary reviews, Tadicherla and Berman examine the
role of noninvasive percutaneous drug delivery systems used in the local control of
pain. They outline the mechanisms of percutaneous absorption of these products and
address their composition, duration of onset of anesthetic effect, and uses and side
effects. The authors also discuss novel advances in the use of heat to enhance anesthetic
penetration, as provided by the SyneraTM patch, and use of a peel method to deliver
anesthesia, such as that provided by S-Caine patch, a product that is currently awaiting
FDA approval. The opioid class of analgesics has proven efficacy and a long history
of use in the management of both acute and chronic pain; however, concerns over their
safety, tolerability and longer-term acceptance to patients have prevented them from
realising their therapeutic promise. Rudolf Likar presents a review of the safety
aspects of the transdermal semisynthetic opioid buprenorphine and highlights the results
of two decades’ work that indicates its superior therapeutic benefits and safety profile.