Evaluation of prescribing pattern of phosphodiesterase-5 inhibitors and assessing effectiveness of sildenafil and tadalafil in patients with erectile dysfunction

Several factors may affect identification and treatment of erectile dysfunction by health care providers, this study evaluates prescribing pattern of PDE-5 inhibitors and assess effectiveness of Sildenafil and Tadalafil in patients with erectile dysfunction.This is a descriptive and observational study, observed participants without providing any interventions, after fulfilling inclusion and exclusion criteria, patients were enrolled into study and informed written consent was obtained from all patients, data was obtained from medical records, analysed descriptively. International Index of Erectile Function (IIEF) Questionnaire is used in assessment of erectile dysfunction and treatment outcomes.In our study, 80% of patients were prescribed with phosphodiesterase inhibitors and 20% received nutritional supplements. 80 percent of drugs were prescribed under generic name, subjects treated with Sildenafil/Tadalafil were found to be associated with higher mean scores for questions of International Index of Erectile Function (IIEF). Tadalafil scored high in terms of sexual desire domain.PDE5 inhibitors represent major first-line oral therapy option for men with erectile dysfunction, shift of market from brand to generic products allows more freedom of choice, although multiple reports suggest general equivalency of four major PDE5 inhibitors, tadalafil suggested to be preferable.

Erectile dysfunction in men with diabetes (literature review). Part 2

The second part of review article highlights modern views on the diagnosis and treatment of erectile dysfunction (ED) in men with diabetes mellitus (DM). Google Scholar and PubMed databases were used to search for literature sources. The role of comorbid diseases in the development of ED in men with diabetes mellitus has been shown. The generalized data on the main clinical manifestations of erectile dysfunction, methods of its diagnosis and treatment are given. A number of epidemiological studies over the past 20 years have found that erectile dysfunction in men with diabetes may be an early marker of cardiovascular complications. Thus, in the algorithm for the diagnosis of ED in patients with diabetes it is necessary to conduct a thorough examination of the cardiovascular system. The article describes modern therapeutic and surgical methods of ED treatment. Numerous literature sources indicate an important role of the correction of androgen deficiency in men with type 2 diabetes to enhance the effectiveness of phosphodiesterase type 5 (PDE5) inhibitors. The literature review shows the data on the emergence of new PDE5 inhibitors, which have a higher selectivity compared to existing ones that provides a better therapeutic effect and reduces the frequency and severity of side effects. The modern algorithm for the treatment of ED in men involves the sequential stages of using different treatments. The last link of therapy, in case of inefficiency of the previous ones, is penile prosthesis. Implantation of three-piece penile prosthesis is an effective method of ED treatment. The use of this method in patients with severe forms of ED on the background of diabetes, in case of ineffectiveness of PDE5 inhibitors and intracavernous injections of vasoactive drugs, is considered promising.

The Effect of Phosphodiesterase-type 5 Inhibitors on Erectile Function: An Overview of Systematic Reviews

Background: Multiple systematic reviews explore the effect of phosphodiesterase type 5 (PDE5) inhibitors on erectile dysfunction (ED), with each study addressing specific outcomes. However, physicians and policymakers require a holistic approach of this topic.Objective: To summarize the current evidence regarding the efficacy and safety of PDE5 inhibitors for the management of ED through an overview of systematic reviews.Methods: Studies were identified by searching PubMed, Web of Science, Cochrane Library and Scopus databases, as well as sources of grey literature until June 12, 2021 (PROSPERO: CRD42020216754). We considered systematic reviews, meta-analyses or network meta-analyses of randomized trials that provided outcomes about the efficacy and safety of any approved PDE5 inhibitor (avanafil, sildenafil, tadalafil and vardenafil). We constructed forest plots for meta-analytic effects regarding the change in erectile function, adverse events and dropouts after administration of PDE5 inhibitors in the general population and in specific patient groups.Results: We included 23 studies with 154,796 participants and a total of 258 meta-analytic effects. Sildenafil 25 mg [Weighted Mean Difference (WMD): 13.08, 95% Confidence Interval (CI): 10.1-16.06] seemed to be statistically superior to all interventions in improving erectile function compared to placebo, but studies with low-dose sildenafil are lacking. Moreover, comparing among different PDE5 inhibitors, sildenafil 50 mg or sildenafil 100 mg were considered the most effective compounds in the general population. The latter derived, however, predominantly from indirect comparisons among different PDE5 inhibitors. Still, sildenafil 100 mg was associated with more treatment-related adverse events and dropouts. Interestingly, low-dose daily tadalafil may be more effective than high-dose on-demand tadalafil (WMD: 1.24, 95% CI: 0.03-2.44). Furthermore, testosterone and PDE5 inhibitors in patients with ED and hypogonadism seem to further improve symptoms, while the addition of a-blockers in patients with urinary symptoms treated with PDE5 inhibitors does not provide additional benefits (WMD: −0.8, 95% CI: −1.65-0.06).Conclusion: Although the efficacy and safety of PDE5 inhibitors, compared to placebo, is well-documented, the existing evidence comparing different PDE5 inhibitors is low. Therefore, high-quality, head-to-head, trials comparing different PDE5 inhibitors are necessary to determine their ideal dosage and formulation based on their safety and efficacy profile.Systematic Review Registration: PROSPERO, identifier [CRD42020216754].

AB0419 ACCESS TO TREATMENT FOR RAYNAUD’S PHENOMENON AND DIGITAL ULCERS FOR PATIENTS WITH SYSTEMIC SCLEROSIS DOESN’T FOLLOW EULAR/EUSTAR GUIDELINES

Background:Patients with Raynaud’s Phenomenon (RP) from systemic sclerosis (SSc) may experience severe complications. Digital ulcers (DUs), occur in approximately half the patients with SSc, and cause hand dysfunction, severe pain, and decreased quality of life. DUs lead to increased healthcare utilization and systemic economic burden through hospitalizations, ED visits, and ambulatory services (1). However, access to medications such as PDE5 inhibitors and prostacyclins that are within the EULAR/EUSTAR SSc guidelines (2) in a country with global health care but patchy pharmacare such as Canada has not been studied.Objectives:The purpose of this study was to elucidate the access to treatment of medications for RP and DU in patients with SSc in Canadian provinces through identifying the provincial and private insurance coverage of PDE5 inhibitors (PDE5i) and prostanoids, the timelines and procedures of requesting these medications, and the process of administering IV prostanoids if required for patient care.Methods:We designed an online survey and collected data through the Survey Monkey platform. The survey was administered to rheumatologists affiliated with the Canadian Scleroderma Research Group (CSRG) from December 2020 to January 2021. Responders were asked to report if the province or private insurance automatically provided PDE5i for patients with RP and DU or if a dedicated process was required to attain these medications. Additionally, responders were asked to describe the process of administering Iloprost, Epoprostenol and Alprostadil and the barriers inherent to their administration. Of note, there is no DIN number for Iloprost in Canada so every time it is used there must be an application to Health Canada.Results:The survey was completed by 100% of CSRG researchers (17/17), representing 8 provinces in Canada. None of the provincial governments provided coverage for PDE5i without special requests that were adjudicated on a case by case basis with approximately half the provinces paying for PDE5i upon special request if a patient was eligible for provincial drug insurance (ex elderly, youths, low income families). Two provinces, Quebec and Saskatchewan, provided PDE5i “all the time”. Whereas NS, MB, ON, BC, and AB provided them “sometimes”; NFLD provided them “never”. Provincial governments and private insurance fulfilled requests “within 1 month” 62% of the time and the other requests took longer to be answered. Private insurance approved coverage with special request in AB, MB, QC, ON, and NS. Respondents described administration of IV prostanoids as “inconsistent”, requiring “a lot of work”, and that patients in most jurisdictions be admitted as in-patients for provinces to cover these medications.Conclusion:Most jurisdiction within Canada do not provide coverage for PDE5i and the process to obtain access for patients is delayed, non-uniform, and often not approved. Intravenous prostanoid infusions are difficult to obtain and have system barriers. Advocacy and cost effectiveness data should be used to advocate for access to medications that are recommended within SSc recommendations.References:[1]Morrisroe K, et al. Digital ulcers in systemic sclerosis: their epidemiology, clinical characteristics, and associated clinical and economic burden. Arthritis research & therapy. 2019 Dec;21(1):1-2.[2]Kowal-Bielecka O, et al. Update of EULAR recommendations for the treatment of systemic sclerosis. Annals of the rheumatic diseases. 2017 Aug 1;76(8):1327-39.Disclosure of Interests:None declared

New Approaches in Oncology for Repositioning Drugs: The Case of PDE5 Inhibitor Sildenafil

The use of already-approved drugs to treat new or alternative diseases has proved to be beneficial in medicine, because it reduces both drug development costs and timelines. Most drugs can be used to treat different illnesses, due their mechanisms of action are not restricted to one molecular target, organ or illness. Diverging from its original intent offers an opportunity to repurpose previously approved drugs to treat other ailments. This is the case of sildenafil (Viagra), a phosphodiesterase-5 (PDE5) inhibitor, which was originally designed to treat systemic hypertension and angina but is currently commercialized as erectile dysfunction treatment. Sildenafil, tadalafil, and vardenafil are PDE5 inhibitors and potent vasodilators, that extend the physiological effects of nitric oxide and cyclic guanosine monophosphate (cGMP) signaling. Although most of the biological implications of these signaling regulations remain unknown, they offer a large therapeutic potential for several diseases. In addition, some PDE5 inhibitors’ molecular effects seem to play a key role in different illnesses such as kidney disease, diabetes mellitus, and cancer. In this review, we discuss the molecular effects of PDE5 inhibitors and their therapeutic repurposing in different types of cancer.