The impact of biologic response modifiers on hepatitis B virus infection

Introduction: The biologic response modifiers are a diverse group of medications that have emerged over the last decade. They target pro-inflammatory cytokines or cell surface molecules that drive illnesses such as rheumatoid arthritis. Despite the greater control afforded they have also ushered in a new spectrum of side effects. As the same immunologic machinery that helps control infections such as HBV contributes to the pathogenesis of rheumatologic diseases, persistence or reactivation of the virus remains an evolving concern.

Areas covered: A systemic literature review was performed using the PubMed and Medline databases (1996 to January 2010) searching for the index term ‘Hepatitis B’ combined with the terms ‘tumor necrosis factor’, ‘B cell’, ‘rituximab’, ‘IL-1’, ‘anakinra’, ‘IL-6’, ‘tocilizumab’, ‘CTLA-4’, and ‘abatacept’. All relevant articles in English were reviewed and secondary references of interest were also retrieved. This paper addresses the role of the various cytokines and cluster of differentiation molecules in controlling HBVinfection and the currently known effect that the biologic response modifiers have on viral control by the host immune response.

Expert opinion: The risk of HBV reactivation is greatest in HBsAg positive patients. These patients should start antiviral therapy one week before receiving a biologic response modifier. The risk of HBV reactivation in HBsAg negative patients appears very low but when HBsAb titers are low use of rituximab or TNF-α antagonists may increase the risk of reactivation.     

Update on biologicals for treatment of juvenile idiopathic arthritis

Introduction: The development of biologics has markedly changed the treatment of JIA. Complete control of the disease and remission has today become the main goal of treatment preventing long-term damage and disability.

Areas covered: This review gives an overview of the current treatment options using biologics in JIA. The biologic drugs are discussed on the basis of recent clinical trials.

Expert opinion: While JIA is a group of heterogeneous diseases, differences in their biology turned out to influence treatment success with different biologics. TNF inhibitors emerged to be the most commonly used biologics for the treatment of JIA. First they were successful for the treatment of rheumatoid factor positive and negative polyarticular JIA. TNF inhibitors have also been studied in patients with enthesitis-related arthritis, psoriatic arthritis, and extended olioarthritis, and approval of at least etanercept is expected. Second-line biologics are abatacept and tocilizumab. For systemic onset JIA, tocilizumab, and the IL-1 inhibitors anakinra and canakinumab have been successfully studied. In the treatment of JIA, biologics have emerged as potent drugs to control the disease. New advancements will be crucial for further improvement of treatment options in JIA.     

siRNA therapy for cancer and non-lethal diseases such as arthritis and osteoporosis

Importance of the field: Gene silencing mediated by siRNA has been widely investigated as a potential therapeutic approach. The success of these therapies depends on effective systems capable of selectively and efficiently conveying siRNA to targeted cells/organs with minimal toxicity.

Areas covered in this review: This review discusses current experimental approaches to siRNA delivery strategies available for arthritis treatment and the management of other musculoskeletal disorders. The review covers literature on the subject from 2000 to 2010.

What the reader will gain: In the last decade, extensive improvements have been made to optimize siRNA-based gene therapy and have been tested on several arthritis and orthopedic conditions. However, except for Phase I – II DNA-based gene therapy trials on arthritis, no clinical studies have reported siRNA application in these domains.

Take home message: Most musculoskeletal disorders, such as rheumatoid arthritis, osteoarthritis, fracture, aseptic loosening, cartilage and intervertebral disc degeneration are non-fatal and age-related chronic inflammatory conditions, but represent significant morbidity and a socio-economic burden. siRNA-based gene therapy offers treatment opportunities that are less invasive, more effective and less expensive than existing modalities. Future directions for siRNA therapy include the development of safe and more efficient delivery systems and the selection of optimal gene targets for disease control.     

HER2 as a target for breast cancer therapy

Importance of the field: Differential levels of HER2 expression in normal versus HER2-overexpressing breast carcinomas, together with the demonstration of a key role for HER2 in tumor progression, make HER2 an ideal target for specific therapeutic approaches.

Areas covered in this review: This review considers the clinical value of trastuzumab and lapatinib, the two HER2-targeted therapies approved for clinical practice. References were chosen by searching the PubMed and MEDLINE datasets using as search term: ‘HER2’, in association with ‘prognosis’, ‘response’, ‘trastuzumab’, ‘lapatinib’ and ‘resistance’.

What the reader will gain: This review deals with HER2 as a target for breast carcinoma treatment, focusing on anti-HER2 therapies used in clinical practice, their merits and shortcomings.

Take home message: The benefit of anti-HER2 therapies demonstrated in clinical trials indicates that HER2 is, to date, one of the most promising molecules for targeted therapy. Nevertheless, since tumor cells utilizing alternative growth signaling pathways through transmembrane receptors as well as intracellular signaling transduction molecules can bypass HER2 blockade, a future ambitious aim is the successful combination of anti-HER2 strategies with drugs directed to molecules that contribute to anti-HER2 resistance.     

Treatment of Pneumocystis jirovecii pneumonia in HIV-infected patients: a review

Introduction: Pneumocystis pneumonia is a potentially life-threatening pulmonary infection that occurs in immunocompromised individuals and HIV-infected patients with a low CD4 cell count. Trimethoprim-sulfamethoxazole has been used as the first-line agent for treatment, but mutations within dihydropteroate synthase gene render potential resistance to sulfamide. Despite advances of combination antiretroviral therapy (cART), Pneumocystis pneumonia continues to occur in HIV-infected patients with late presentation for cART or virological and immunological failure after receiving cART.

Areas covered: This review summarizes the diagnosis and first-line and alternative treatment and prophylaxis for Pneumocystis pneumonia in HIV-infected patients. Articles for this review were identified through searching PubMed. Search terms included: ‘Pneumocystis pneumonia’, ‘Pneumocystis jirovecii pneumonia’, ‘Pneumocystis carinii pneumonia’, ‘trimethoprim-sulfamethoxazole’, ‘primaquine’, ‘trimetrexate’, ‘dapsone’, ‘pentamidine’, ‘atovaquone’, ‘echinocandins’, ‘human immunodeficiency virus infection’, ‘acquired immunodeficiency syndrome’, ‘resistance to sulfamide’ and combinations of these terms. We limited the search to English language papers that were published between 1981 and March 2017. We screened all identified articles and cross-referenced studies from retrieved articles.

Expert commentary: Trimethoprim-sulfamethoxazole will continue to be the first-line agent for Pneumocystis pneumonia given its cost, availability of both oral and parenteral formulations, and effectiveness or efficacy in both treatment and prophylaxis. Whether resistance due to mutations within dihydropteroate synthase gene compromises treatment effectiveness remains controversial. Continued search for effective alternatives with better safety profiles for Pneumocystis pneumonia is warranted.     

Brodalumab-an IL-17RA monoclonal antibody for psoriasis and psoriatic arthritis

Introduction: IL-17 is a growing target for autoimmune and inflammatory diseases. Brodalumab is a fully human anti-IL-17RA monoclonal antibody that has been investigated in a range of disease including psoriasis, psoriatic arthritis, rheumatoid arthritis, inflammatory bowel disease and asthma.

Areas covered: This review aims to summarize up-to-date pharmacological properties of brodalumab and the clinical efficacy and safety data presented in clinical trials. The focus of this review will be on psoriasis, psoriatic arthritis and rheumatoid arthritis although we will briefly touch on the other indications in which the drug has been studied as we feel it adds to our understanding of the IL-17 pathway and highlights areas where research is still needed.

Expert opinion: Brodalumab has shown good efficacy in psoriasis in small but extended studies with a moderate effect on psoriatic arthritis. Brodalumab studies are clearly negative in rheumatoid arthritis and inflammatory bowel disease. The data are equivocal in asthma; however, further studies in this disease are justifiable. The safety profile of this drug thus far is not worrisome although longer studies in more patients are needed.     

Tumour necrosis factor inhibitors in the treatment of psoriatic arthritis: a view on effectiveness,clinical practice and toxicity

Introduction: Psoriatic arthritis is a common and often severe chronic joint disorder associated with the skin disease psoriasis (PsO). Treatment options for psoriatic arthritis patients have changed considerably over the last decade with the widespread use of biological therapies, in particular tumour necrosis factor inhibitors. Current clinical experience based on large registries and careful observations now allows us to understand the true value of these interventions in daily clinical practice.

Areas covered: Literature searches were performed targeting effectiveness, drug survival, toxicity and safety of biological therapies as well as treatment strategies specifically focused on patients with psoriatic arthritis.

Expert opinion: Tumour necrosis factor inhibition is a powerful and effective option for the treatment of severe psoriatic arthritis. The different available drugs have good survival rates and show an excellent balance between effectiveness and toxicity. Switching of inhibitor is feasible, but treatment changes should be carefully considered. Novel biological therapies are introduced into the market and will further provide better perspectives for the patient. New questions are also emerging: How to handle long-term remission, can biological therapies be successfully stopped and are co-morbidities sufficiently managed? These questions should be addressed for optimal long-term management of a severe chronic disease.     

The use of ustekinumab in autoimmune disease

Importance of the field: The advent of biologic therapies has revolutionized the treatment of autoimmune diseases including psoriasis, autoimmune arthritides and inflammatory bowel disease. With recent advances in our understanding of the immunogenetic pathways involved in the pathogenesis of these conditions, newer, more targeted biologic therapies have been developed. Ustekinumab is an antibody to the common p40 subunit of IL-12 and IL-23, which has been studied in the treatment of psoriasis, psoriatic arthritis, Crohn's disease and multiple sclerosis.

Areas covered in this review: This review details the efficacy and safety of ustekinumab in all clinical studies to date, using PubMed listed publications and official product websites.

What the reader will gain: Readers will gain a comprehensive understanding of the mechanism of action of ustekinuamb, its pharmacodynamic and pharmacokinetic profile, and its clinical efficacy and safety in the treatment of psoriasis, psoriatic arthritis, Crohn's disease and multiple sclerosis.

Take home message: Ustekinumab has shown significant efficacy in the treatment of chronic plaque psoriasis in Phase III studies, and promising results in Phase II studies in psoriatic arthritis. Efficacy has been shown in Crohn's disease only in non-responders to infliximab. Ustekinumab did not show benefit in the treatment of multiple sclerosis.     

Team-based rehabilitation improves long-term aerobic capacity and health-related quality of life in patients with chronic inflammatory arthritis

Purpose.?To examine the effect of an interdisciplinary, out-patient rehabilitation programme for patients with chronic inflammatory arthritis on aerobic capacity and health-related quality of life (HRQOL).

Method.?One hundred and seventy-four patients, 115 with peripheral arthritis (PA) (91 women, mean age 53 years, disease duration 16 years) and 59 with spondylarthropathies (SpA), (27 women, mean age 46 years, disease duration 14 years) were consecutively enrolled in 18 days of interdisciplinary rehabilitation. We report data from evaluations at inclusion, at discharge, and at 4 and 12 months using a sub-maximal treadmill test of aerobic capacity and the Nottingham Health Profile (NHP) (t-test).

Results.?At inclusion, less than 20% of all patients tested had aerobic capacity classified as ‘average’ or better. At discharge, 41% (PA) and 54% (SpA) reached the ‘average’ level or better with improvements maintained for 12 months. The total NHP scores improved in both groups (mean change??12 (99%CI –15, –9) for PA; mean change –13 (99%CI –19, –8) for SpA) and were maintained.

Conclusion.?Aerobic capacity and HRQOL improved significantly in this interdisciplinary out-patient rehabilitation study, and improvements were maintained for 12 months. The preserved level of aerobic capacity after 12 months indicated a change to a more physically active lifestyle among the participants.     

Educational session as a tool to increase patient satisfaction of switching etanercept from the prefilled syringe to the autoinjection pen

Objective: To assess patients' acceptability of switching etanercept from the prefilled syringe to the autoinjection pen in rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis patients.

Methods: A two-phase cross-sectional study was designed. First phase: consisted of a 2 h information/education session to present the pen and learning its use. At the end of the session, patients completed a self-administered questionnaire regarding the meeting usefulness. Second phase: eight single-use prefilled Enbrel® Pen Myclic were provided.

Results: The number of patients included were 104 (rheumatoid arthritis 58, psoriatic arthritis 31, ankylosing spondylitis 15). Attendees showed a high satisfaction degree with the meeting. A high percentage of patients (74.4 – 95.1%) rated the items of the questionnaire as ‘very much'. Patients reported > 95% adherence to etanercept autoinjection pen. The percentage of patients self-administering etanercept increased from 66 to 94% and the percentage of those attending primary care for injection decreased from 23 to 2%. It produced important cost savings, in our study represents > 22.000 euros/year. Pain at the injection site was significantly reduced with the use of autoinjection pen. Ninty seven (93%) patients considered that the use of the autoinjection pen was easier than the syringe and 94.2% chose the pen as their preferred delivery system.

Conclusions: The autoinjection pen is an advantageous delivery option for etanercept. This study provides further evidence to support that the education strategy is a valid method for switching anti-TNF-α drugs from syringe to pen in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis.     

Long-term safety,efficacy, and immunogenicity of adalimumab biosimilar BI 695501 and adalimumab reference product in patients with moderately-to-severely active rheumatoid arthritis: results from a phase 3b extension study (VOLTAIRE-RAext)

ABSTRACT

Objective: To evaluate long-term safety, efficacy, and immunogenicity of BI 695501 in patients with moderately-to-severely active rheumatoid arthritis (RA) who have completed VOLTAIRE-RA.

Methods: Eligible patients for this phase 3b open-label extension study (VOLTAIRE-RAext), who had completed 48 weeks’ treatment with BI 695501 (Group A), 24 weeks each of adalimumab RP then BI 695501 (Group B), or 48 weeks of adalimumab RP (Group C) in VOLTAIRE-RA, were enrolled.

Results: Altogether, 430 patients received BI 695501 fortnightly for 48 weeks: Group A, n = 225; Group B, n = 103; Group C, n = 102. The proportion of patients with drug-related adverse events (AEs; overall 20.2%) was similar across Groups A, B, and C: 21.3%, 20.4%, and 17.6%, respectively. The majority of treatment-emergent AEs were non-serious and of mild/moderate intensity. Consistent with adalimumab RP’s safety profile, most drug-related AEs were in the system organ class infections and infestations. BI 695501 and adalimumab RP responses at the end of VOLTAIRE-RA were sustained during VOLTAIRE-RAext and all efficacy and immunogenicity endpoints were similar across groups.

Conclusion: Over 2 years, BI 695501 showed similar safety, efficacy, and immunogenicity to adalimumab RP, independent of initial treatment in VOLTAIRE-RA. No previously unknown adalimumab side effects were identified.

Clinical trial registration: NCT02640612.     

The importance of optimal drug sequencing in metastatic colorectal cancer: biological rationales for the observed survival benefit conferred by first-line treatment with EGFR inhibitors

Introduction: Use of both the vascular endothelial growth factor (VEGF) inhibitor bevacizumab and the epidermal growth factor receptor (EGFR) inhibitors cetuximab and panitumumab as potential first-line therapies for patients with RAS-wild-type metastatic colorectal cancer presents clinicians with an important decision. We review clinical data evaluating first-line treatment with EGFR inhibitors. Additionally, by undertaking an integrated ‘bench-to-bedside’ approach, we provide potential models, testable hypotheses and biological rationales that might account for these clinical observations.

Areas covered: A literature search encompassing PubMed and the ASCO/ESMO websites was undertaken in October 2014. Search terms included ‘colorectal cancer’, ‘cetuximab’, ‘panitumumab’ and ‘bevacizumab’.

Expert opinion: A number of clinical studies indicate a survival benefit for patients receiving EGFR inhibitors in combination with chemotherapy in the first-line setting, relative to both chemotherapy alone and VEGF inhibitors plus chemotherapy. Existing preclinical and clinical data suggest that a biological basis exists for providing RAS-wild-type patients with first-line EGFR inhibitors, followed by second-line VEGF inhibitors. More specifically, first-line treatment with EGFR inhibitors may elicit unique biological changes that sensitize tumors to subsequent lines of therapy; conversely, first-line treatment with VEGF inhibitors may elicit biological changes that desensitize tumors to subsequent lines of therapy.     

Measurement properties of patient-reported hand function measures in rheumatoid arthritis: a systematic review protocol

Background: Patient-reported outcome measures (PROMs) are commonly used to evaluate hand function in people with rheumatoid arthritis (RA). A decision will always need to be made about which appropriate PROMs to use. The present review therefore aims to describe the available hand function PROMs for use in people with RA by appraising their methodological quality and psychometric properties using a contemporaneous method.

Methods/design: The proposed systematic review will include published studies written in English, which report evidence for psychometric properties and/or practical properties of hand function PROMs in RA. Four major databases (MEDLINE, Embase, PsycINFO, and CINAHL) will be searched from inception to May 2019. A three-staged search strategy will be applied: (1) electronic bibliographic databases for published studies, (2) ‘named measures’ searching approach, and (3) reference lists of studies with included PROMs. The proposed systematic review will be conducted in compliance with the consensus-based standards for the selection of health measurement instruments (COSMIN) guideline for systematic review of PROMs. Accordingly, the methodological quality of the included studies will be assessed against the updated COSMIN risk of bias checklist, and each study’s results will be assessed for their psychometric quality.

Conclusion: The proposed systematic review seeks to provide rigour, and transparent evaluation of PROMs used to evaluate hand function in the RA population. The findings will provide clarity for healthcare professionals and researchers on the appropriate PROMs for hand function assessment. It will also provide a summary of hand function PROM recommendations for RA.     

Modulation of toll-like receptor function has therapeutic potential in autoimmune disease

Importance of the field: The role of toll-like receptors (TLRs) in the immune response to exogenous pathogens is well characterized. These receptors have been suggested to be involved in the initiation and/or perpetuation of many inflammatory autoimmune diseases and have become attractive candidates for the modulation of inflammation.

Areas covered in this review: This review discusses the evidence to support a potential role for TLRs in inflammatory diseases, focusing on rheumatoid arthritis, multiple sclerosis and systemic lupus erythematosus. The approaches to targeting TLR activation are outlined.

What the reader will gain: An appreciation for the role of TLRs in inflammatory diseases and in particular the contribution of specific TLRs in rheumatoid arthritis, multiple sclerosis and systemic lupus erythematosus. This review focuses on recent developments in targeting TLR activity from ligand binding through to the resultant signaling.

Take home message: As initiators of immune responses, TLRs have previously been targeted to increase the immune response with some success. However, targeting TLRs to attenuate immune responses for the treatment of chronic inflammatory diseases will require further evidence of the mechanisms of TLR involvement in the pathophysiology and a better understanding of the potential effects of modulating TLR physiology over a sustained period.     

Pharmacotherapy of haemophilia A

Introduction: Haemophilia A is due to factor VIII (FVIII) deficiency. The main treatment is replacement therapy with FVIII concentrates. However, these concentrates carried a high risk of blood-borne viral infections and still have a high risk of inducing anti-FVIII inhibitors.

Areas covered: An overview of products available and therapeutic options for haemophilia A management in order to help in decision making. A literature search using Medline with the keywords: ‘haemophilia’, ‘factor VIII’, ‘therapy’, ‘inhibitor’, ‘concentrate’, ‘bleeding’, ‘prophylaxis’, ‘on demand’, ‘plasma-derived’, ‘recombinant’, ‘coagulation factors’, ‘immunotolerance’ was performed. The years 1960 – 2010 are included.

Expert opinion: Progress in management of patients with haemophilia A has allowed increased life expectancy and quality of life. There is evidence that prophylaxis prevents or, at least, slows down arthropathy development when started early in childhood. FVIII concentrates have achieved high levels of blood-borne pathogen safety. However, treatment is frequently complicated by development of FVIII-neutralizing inhibitors, which prevent control of bleeding and predispose to a high morbidity and mortality risk. Bypassing agents are effective in bleeding treatment in a high percentage of cases. Prophylaxis with bypassing agents and their use in combination are offering opportunities in management of inhibitor patients. More evidence is necessary to understand how to prevent and manage this complication.     

Development and clinimetric testing of willingness to pay tool for physiotherapy

Background: Lack of technical knowledge on Willingness to Pay (WTP) for health services may have contributed to paucity of WTP studies in physiotherapy.

Objective: To develop and establish clinimetric properties of WTP tool for physiotherapy.

Methods: A WTP tool with five sections exploring information on socio-demographics, physiotherapy experience, satisfaction with physiotherapy, cost of physiotherapy services and patients’ preferences for physiotherapy was developed. The WTP tool was tested for content validity, readability and thereafter completed on test–retest after one-week interval by 97 consenting physiotherapy outpatients. Intra-class correlation coefficient (ICC) with 95% confidence intervals and Cronbach’s alpha (α) were used to assess the data for reliability and internal consistency.

Results: The tool's readability indicated a Flesch-Kincaid Grade Level and Reading Ease scores of 5.6 and 66.7 respectively. ICC for aggregate score of ‘patients’ satisfaction’ was ‘moderate’ (0.644, p?<?0.05), while the ‘cost of physiotherapy services’ section was ‘excellent’ (0.837, p?<?0.05). The internal consistency of the ‘satisfaction with physiotherapy’ (0.783, p?<?0.05) and ‘cost of physiotherapy services’ (0.911, p?<?0.05) sections were ‘excellent’. The stability of the different sections of the instrument over one week period, as reflected by the ICC, ranged from ‘poor’ to ‘excellent’. Also, the Cronbach’s alpha and the ICC for the WTP characteristics were ‘poor’ to ‘excellent’, respectively.

Conclusion: The WTP tool for physiotherapy appears comprehensible and reliable among patients with chronic conditions attending the physiotherapy clinic. Availability of this WTP tool will promote studies examining the demand for physiotherapy services.     

Association of rheumatoid arthritis disease activity and antibodies to periodontal bacteria with serum lipoprotein profile in drug naive patients

Abstract

Objective: We investigated lipid concentrations, particle sizes and antibodies binding to periodontal bacteria Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis and to malondialdehyde-acetaldehyde (MAA) modified low-density lipoprotein in immunoglobulin (Ig) class A, G and M among patients with newly diagnosed rheumatoid arthritis (RA) in a population-based cohort.

Methods: Concentrations and sizes of lipoprotein particles analysed by proton nuclear magnetic resonance spectroscopy and antibody levels to MAA modified low-density lipoprotein were studied at baseline and after one-year of follow-up. Serum Ig A and G class antibodies to periodontal bacteria were determined at baseline.

Results: Sixty-three patients were divided into tertiles according to disease activity by disease activity score with 28 joint count and erythrocyte sedimentation rate (ESR) (<3.9, 3.9–4.7, >4.7). Small low-density lipoprotein concentration was lowest in the tertile with the highest disease activity. In high-density lipoprotein, the concentrations of total, medium and small particles decreased with disease activity. The particle size in low-density lipoprotein associated with disease activity and the presence of antibodies to P. gingivalis. Ig G and M antibodies to MAA modified low-density lipoprotein correlated with disease activity. Inflammation associated changes faded by one year.

Conclusions: Drug naive RA patients had proatherogenic changes in lipid profiles, but they were reversible, when inflammation diminished.

• Key messages

• Patients with drug naive rheumatoid arthritis showed proatherogenic lipid profiles.

• Reversible changes in lipid profiles can be achieved as response to inflammation suppression.

• Active therapy aimed at remission is essential in all patients with rheumatoid arthritis.

     

Botulinum toxin in urology: a review of clinical potential in the treatment of urologic and sexual conditions

Introduction: In recent years, there has been an increased interest in the use of botulinum neurotoxin (BoNT) to treat medical conditions refractory to conventional treatment. The following article provides an overview of the clinical use and efficacy of BoNT in the treatment of various urologic and sexual conditions.

Areas covered: BoNT has been accepted and/or explored as novel treatment for various lower urinary tract and sexual dysfunctions such as overactive bladder/detrusor overactivity (DO), detrusor-sphincter dyssynergia (DSD), benign prostatic hyperplasia, interstitial cystitis/painful bladder syndrome, chronic pelvic pain and more recently premature ejaculation. The following terms ‘botulinum toxin’, ‘BoNT’, ‘botulinum toxin A’, ‘Botox’, ‘Dysport’, ‘Xeomin’, ‘botulinum toxin B’, ‘Myobloc’, ‘OnabotulinumA’, ‘RimabotulinumA’, ‘IncobotulinumA’ and ‘AbobotulinumA’ were used to search several databases including MEDLINE, Pubmed, EMBASE, CINAHL and clinicaltrials.gov for inclusion in this review article. Only English language articles were considered and all studies were limited to BoNT therapy in urological conditions in the adult population.

Expert opinion: BoNT-A has received regulatory approval for use in neurogenic DO and overactive bladder, but its use remains unlicensed in other lower urinary tract conditions such as non-neurogenic lower urinary tract symptoms in men with benign prostatic hyperplasia, bladder pain syndrome and DSD. Published literature shows that BoNT can be effective in carefully selected patient groups, has minimal adverse event profile and is generally well tolerated by many patients. However, many questions remain unanswered and larger scale multi-institutional studies are required to determine the key factors in BoNT treatment success.