Ixekizumab for the treatment of psoriasis: up-to-date

ABSTRACT

Introduction: Ixekizumab (an IL-17A antagonist) is a biologic therapeutic licensed for use in moderate-to-severe plaque psoriasis and psoriatic arthritis. IL-17 antagonists (also including Secukinumab and Brodalumab) represent a new generation of biologic therapy with rapid and high response rates, quickly becoming a crucial part of the psoriasis treatment armamentarium.

Areas covered: In this review, we describe how IL-17A antagonists disrupt inflammatory cascades in psoriasis and summarize results from clinical trials examining the safety and efficacy of ixekizumab against placebo and comparators.

Expert opinion: Ixekizumab induces a 75% reduction in psoriasis area severity index (PASI 75) in 89% of patients after 12 weeks and after 1 year, PASI 75 is maintained in 80% of patients. Ixekizumab is superior to both etanercept and ustekinumab, however, further comparator trials are needed to determine superiority between newer agents. Network meta-analysis suggests that ixekizumab is one of the most rapid and efficacious agents for treating psoriasis, but ideally more long-term real-world data are needed to determine the persistence of response. Candida may be commonly encountered during treatment and IL-17 agents should be avoided in patients with inflammatory bowel disease. Overall, ixekizumab represents an efficacious and well-studied therapeutic that can offer biologic-naïve and bio-failure patients durable disease control.     

Bimekizumab for the treatment of psoriatic disease

ABSTRACT

Introduction: Psoriasis and psoriatic arthritis are common diseases with significant physical and emotional burden. Several biologics are FDA-approved to treat psoriasis and psoriatic arthritis, though some patients remain refractory to, or have lost response to, therapy and/or cannot tolerate the associated risks and side effects. Bimekizumab is a new biologic that inhibits both IL-17A and IL-17F. It is currently in phase III clinical trials. To date, phase II studies show promise in its ability to rapidly resolve symptoms while remaining safe and well-tolerated.

Areas covered: This review serves to summarize the literature regarding the use of bimekizumab for psoriasis and psoriatic arthritis. Bimekizumab has undergone phase I and phase II clinical trials with results showing significant disease improvement or resolution, as well as safety and tolerability. Phase III studies are now actively enrolling.

Expert opinion: Bimekizumab is a burgeoning biologic offering significant promise through its unique bispecific targeting of both IL-17A and IL-17F. Clinical trials have shown the potential of rapid symptom improvement after treatment with bimekizumab, with some patients seeing improvement after only two weeks. To date, bimekizumab has been shown to be safe and well-tolerated by patients, without any associated significant adverse events.     

Ixekizumab: an anti- IL-17A monoclonal antibody for the treatment of psoriatic arthritis

Introduction: Psoriatic arthritis (PsA) is an inflammatory rheumatic disease that manifests itself with synovitis, dactylitis, enthesitis and also axial involvement. Interleukin-17A has been identified as a master cytokine in the inflammatory response and pathogenesis of PsA and spondyloarthritis in general. Ixekizumab is a new humanized monoclonal antibody that blocks the biological activity of IL-17A. This biological agent has previously demonstrated a high level of efficacy in psoriasis.

Areas covered: This review discusses the basic immunology of the IL-17 cytokine family, the contribution of IL-17A to the immunopathogenesis of PsA, the clinical trials that evaluated ixekizumab in patients with PsA (SPIRIT program) and the safety of this agent.

Expert opinion: Ixekizumab demonstrated its efficacy in different aspects of PsA including peripheral joint involvement, dactylitis, skin symptoms and patient reported outcomes in the 2 phase III trials from the SPIRIT program. Its safety profile was consistent with previous observations in patients with psoriasis. The role of IL-17A in the management of patients with PsA needs further clarification. According to EULAR recommendations for the management of PsA, IL-17A inhibitors may be used as second line biological DMARDs after TNF inhibitors.     

Targeting the IL-23/IL-17 axis for the treatment of psoriasis and psoriatic arthritis

Introduction: A growing amount of data supporting the pathogenic role of the IL-23/IL-17 axis in inflammatory/autoimmune disorders has provided the rationale to target the system for therapeutic purpose. Several compounds have been and are currently under intense investigation in psoriasis and psoriatic arthritis (PsA) yielding impressive results.

Areas covered: In this review article, we provide an overview of currently available data on the IL-23/IL-17 system as a target for treatment for psoriasis and PsA. We searched MEDLINE for articles on drug therapy for psoriasis and PsA published between 1 January 2010 and 31 May 2015. One of these agents, ustekinumab, has been recently approved for the treatment of psoriasis and PsA, and a number of IL-23/IL-17-targeted compounds under investigation in these diseases.

Expert opinion: As our knowledge of the role of the IL-23/IL-17 axis in the pathogenesis of psoriasis and PsA deepens, it enables the development of more targeted therapies in the management of these conditions. Early data on IL-23/IL-17 targeting drugs appear promising, although incomplete. Given the key role IL-23/IL-17 in host defence, the safety profile of targeted drugs should be thoroughly assessed in future studies.     

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.     

Anti-IL17 therapies for psoriasis

Introduction: Interleukin-17 (IL-17) is a proinflammatory cytokine considered to play a significant role in the immunopathogenesis of plaque psoriasis. As a result, focus in clinical trials has undergone a shift towards disease specific targets, with the goals of more effective treatment and reduction in the incidence of serious adverse events.

Areas covered: Two monoclonal antibodies targeting IL-17A (secukinumab, ixekizumab) and one against the IL-17 receptor (brodalumab) are approved for the treatment of moderate-to-severe plaque psoriasis. Herein, the clinical efficacy, safety and tolerability of each is reviewed by summarizing the existing literature (found via PubMed database).

Expert commentary: The development and approval of the IL-17 inhibitor agents secukinumab, ixekizumab, and brodalumab has expanded psoriatic treatment with effective options, validating the importance of the pro-inflammatory role of IL-17 psoriatic pathophysiology. Biologic treatment options for psoriasis will continue to grow, especially IL-17 and IL-23 related agents, with an increasing specificity of agents to be available in the future.     

Biologics that inhibit the Th17 pathway and related cytokines to treat inflammatory disorders

Introduction: Advances in the understanding of TNF-α and IL-17 synergistic functions have recently led to the concept that patients who do not respond or who respond inadequately to TNF-α inhibitors may have IL-17-driven diseases, opening up the way for a new class of therapeutic development: Th17-inhibitors.

Areas covered: In this review, the authors discuss the central role that the IL-23/Th17 axis plays in the pathogenesis of several inflammatory diseases, such as psoriasis, highlighting its position as a relevant therapeutic target. In particular, the authors start by giving a brief historical excursus on biologic agent development up until the success of TNF-α inhibitors, and continue with an overview of IL12/23 pathway inhibition. Next, they describe Th17 cell biology, focusing on the role of IL-17 in host defense and in human immune-inflammatory diseases, discussing the use and side effects of IL-17 inhibitors.

Expert opinion: The IL-23/Th17 signaling pathway plays a central role in the pathogenesis of several inflammatory diseases, such as psoriasis. Recent data has demonstrated that biologics neutralizing IL-17 (ixekizumab, secukinumab) or its receptor (brodalumab) are highly effective with a positive safety profile in treating moderate to severe psoriasis, offering new treatment possibilities, especially for patients who do not respond adequately to anti-TNF-α therapies.     

Biological therapies for psoriasis

Introduction: Biological therapies have revolutionized moderate-to-severe psoriasis treatment. Increased understanding of disease pathogenesis has yielded multiple therapeutic targets involving the IL-23/Th17 pathway, while current therapies continue to be monitored for long-term efficacy and safety.

Areas covered: This review details current understanding of psoriasis immunopathogenesis specifically related to therapeutic targets. Approved and emerging biological psoriasis therapies targeting TNF-α, IL-12/23p40, IL-17 and IL-23p19 are covered. Biological agent uses in special circumstances are reviewed together with the emerging debate on biosimilar therapies and their potential future role in psoriasis and other inflammatory diseases.

Expert opinion: Psoriasis treatment has expanded and has become more effective due to increased understanding of disease pathogenesis. However, lack of efficacy in select psoriasis patients, safety concerns and limited treatment efficacy in psoriasis variants (e.g., pustular) are areas which still need improvement. As such, pharmacogenomics will be of vital importance in future for individualized psoriasis care. Further, a better understanding of the multiple psoriasis comorbidities, especially cardiovascular disease, continues to be of significant interest in the psoriasis community. Last, the emergence of biosimilar agents has the potential to change psoriasis treatment, especially as it relates to better access for the psoriasis community worldwide.     

Ustekinumab for the treatment of psoriasis and psoriatic arthritis: a drug evaluation and literature review

Introduction: Psoriasis (PsO) is an inflammatory disorder characterized by proliferation of keratinocytes, and it may be associated with a systemic inflammatory articular disorder, psoriatic arthritis (PsA). The presentations of PsO and PsA are heterogeneous, and our understanding of pathogenesis has led to a better understanding of the role of the interleukin (IL)-23/T-helper 17 (Th17) axis.

Areas covered: Ustekinumab is a monoclonal antibody against IL-12 and IL-23. The pathogenesis of PsO and PsA is a multifactorial process involving genetic, environmental, and lifestyle factors. IL-23 signaling and activation of Th17 cells leads to a self-perpetuating inflammatory loop resulting in continuous keratinocyte proliferation and synovitis. Treatment options are varied, ranging from topical therapy to injection of targeted biologic disease-modifying antirheumatic drugs (bDMARDs). Evidence on the use of ustekinumab in the management of PsO is strong, but it is not as impressive in management of PsA.

Expert opinion: IL-12/23 inhibition appears to be a good first-line option for plaque PsO, but efficacy in PsA does not compare favorably to IL-17 inhibition. In general, poorer responses to therapy with any bDMARD in PsA cohorts highlight psoriatic disease heterogeneity. Until new knowledge can remedy the failure of monotherapy, synergistic methods may have to be explored, including combination biologic therapy.     

Novel approaches to biological therapy for psoriatic arthritis

ABSTRACT

Introduction: Improved understanding of the immunopathogenic mechanisms in psoriatic arthritis (PsA) has led to the development of targeted biological therapies, which demonstrate superior clinical efficacy to traditional disease-modifying antirheumatic drugs (DMARDs). There are currently 3 classes of biological agents that are approved for the treatment of psoriatic disease: tumor necrosis factor alpha inhibitors (TNFi), including etanercept, infliximab, adalimumab, golimumab, and certolizumab pegol; ustekinumab, a monoclonal antibody (mAb) directed against interleukin (IL)-12 and IL-23; and secukinumab, a human anti-IL-17A mAb. Other agents are in development. Our growing experience with these medications has revolutionized the approach to disease management in PsA.

Areas covered: This article discusses the rationale for using biological therapies in PsA, highlighting clinical trial evidence that supports the use of these agents. We summarize novel treatment approaches using biological therapies in the management of PsA, including early intervention, targeted therapy, TNFi switching, combination therapy, and tapering or discontinuation of biological therapy. We conclude with a discussion of the importance comorbidities have on selection of therapy.

Expert opinion: The advent of highly effective biological therapies has revolutionized the management of patients with PsA. Growing experience with these agents has led to novel treatment approaches that may improve clinical outcomes for PsA patients.     

Secukinumab in moderate-to-severe plaque psoriasis: a multi-center,retrospective, real-life study up to 52 weeks observation

Objectives: To evaluate efficacy and safety of the anti-IL-17 drug secukinumab in a real-life large cohort of patients with moderate-to-severe plaque psoriasis in Central Italy.

Methods: Multicenter, retrospective study with an observation period of up to 52 weeks. Efficacy was assessed by Psoriasis Area and Severity Index (PASI) score; clinical and laboratory examinations were performed at baseline and at weeks 4, 12, 24, 36, and 52.

Results: A 90% and a 100% PASI score reduction (PASI90 and PASI100) were reported in 67.5% and 55% of patients at week 12, respectively. A rapid improvement of skin lesions was observed particularly in young patients and in patients naïve to biologics: at week 4, the achievement of PASI90 and PASI100 was higher in younger patients (odds ratio [OR] 0.95, and 0.95; p = 0.003, and 0.005, respectively); PASI90 was achieved by 42.0% of patients naïve to biologics and by 17.0% of patients with prior exposure to biologics (PBT) (OR 0.24; p = 0.001); and PASI100 was reached by 25.5% of naïve patients and 9.8% of PBT (OR 0.28; p = 0.015).The drug was well tolerated.

Conclusion: Secukinumab was effective in this real-life analysis, with rapid clinical improvement and long-term maintenance of results.     

Biologics for treating axial spondyloarthritis

Introduction: Spondyloarthritis (SpA) encompasses a heterogeneous group of diseases sharing genetic, immunological, clinical and imaging features. Axial spondyloarthritis (axSpA) refers to a subgroup characterised predominately by inflammation of the axial skeleton with subsequent symptoms of chronic (often inflammatory) back pain and sacroiliitis. There is a strong association with the major histocompatibility complex (MHC) class I allele human leukocyte antigen (HLA) B27. In the last decade, there has been significant progress in earlier detection of the disease and the molecular mechanisms involved in its pathogenesis. The subsequent introduction of anti-tumour necrosis factor (TNF) has revolutionised the treatment of patients with axSpA.

Areas covered: In this article, we review the current biologic therapies for axSpA, the emergence of biosimilars, predictors of response, primary and secondary failure and new biologics on the horizon.

Expert opinion: There have been significant advances in the treatment of axSpA. Beyond the clear efficacy of anti-TNF inhibition, IL-17 offers an alternative therapeutic target and there is promise from inhibition of the IL-17/IL-23 pathway and small molecules, such as Janus kinase (JAK) inhibitors. Biosimilars have offered greater affordability and choice within this increasingly growing field of therapeutics.     

Relationships of interleukin-17 polymorphisms with recurrent aphthous ulcer risk in a Han Chinese population

ObjectiveInterleukin (IL)-17 is a multifunctional cytokine with important roles in inflammatory and autoimmune diseases. This case–control study explored the relationships of IL-17A rs2275913 and IL-17F rs763780 single-nucleotide polymorphisms (SNPs) with recurrent aphthous ulcer (RAU) morbidity and severity.MethodsIL-17A rs2275913 and IL-17F rs763780 SNPs were measured in 125 patients with RAU and 116 healthy control participants. The genotype distributions, disease risks, and relationships with RAU severity were analyzed.ResultsRAU risk was associated with rs2275913 after adjustment for age, body mass index, sex, smoking status, and drinking status (AA vs. GG: odds ratio [OR], 2.759; 95% confidence interval [CI], 1.381–5.512; A allele vs. G allele: OR, 1.783; 95% CI, 1.242–2.560). TC and CC genotypes in rs763780, and the corresponding C allele, demonstrated greater prevalence among patients with RAU, compared with the TT genotype (TC vs. TT, OR: 1.895; 95% CI: 1.088–3.301; CC vs. TT, OR: 4.080, 95% CI: 1.079–15.425; C allele vs. T allele, OR: 1.969, 95% CI: 1.257–3.083). Serum IL-17 concentrations were also higher in patients with RAU than in control participants. These concentrations were associated with IL-17 polymorphisms.ConclusionsIL-17 polymorphisms might be associated with greater risk of RAU pathogenesis.     

Presentation and impact of catheter-associated thrombosis in patients with infected long-term central venous catheters: a prospective bicentric observational study

Background: Catheter-associated thrombosis (CAT) in patients with infected long-term central venous catheter (LTCVC) has been poorly studied. Methods: We prospectively included patients with infected LTCVC and collected clinical data. Doppler ultrasound was systematically performed to screen for CAT. Outcome (death or infection relapse) was evaluated 12 weeks after infection diagnosis. Results: 90 patients were included and CAT was diagnosed in 27 (30%). Local signs suggesting infection were more frequent in patients with CAT than without (11/27 versus 8/63, p?=?0.03). Outcome was similar in patients with and without CAT. However, median duration of antimicrobials was longer (18 versus 14 days, p?=?0.02), catheter removal tended to be more frequent (24/27 versus 46/63, p?=?0.08), and anticoagulant therapy more often prescribed (17/27 versus 6/63, p?Staphylococcus aureus infections (4/7 versus 1/17, p?=?0.02) and prolonged positivity of blood-cultures (3/7 versus 1/15, p?=?0.02), than patients with non-occlusive thrombosis. Conclusion: CAT is associated with local signs suggesting infection. A more aggressive treatment in CAT cases allowed a similar outcome at 12 weeks between patients with and without CAT. Occlusive thrombosis represented a subgroup of patients at risk of delayed clearance of bacteremia.

• KEY MESSAGES

• 30% of patients with infected long-term central venous catheter had catheter-associated thrombosis (CAT) and 89% of patients with CAT had no symptom specifically suggestive of thrombosis.

• More aggressive treatment (catheter removal, anticoagulant therapy and prolonged antimicrobial therapy) in patients with CAT allowed a similar outcome at 12 weeks than in patients without CAT.

• Occlusive thrombosis represented a subgroup of patients at risk of delayed bacteremia clearance.

     

Biological therapy targeting the IL-23/IL-17 axis in inflammatory bowel disease

Introduction: As many inflammatory bowel disease (IBD) patients do not benefit from long-term anti-tumour necrosis factor treatment, new anti-inflammatories are urgently needed. After the discovery of the interleukin (IL) 23/17 axis being pivotal in IBD pathogenesis, many different compounds were developed, targeting different components within this pathway.

Areas covered: A literature search to March 2016 was performed to identify the most relevant reports on the role of the IL-23/IL-17 axis in IBD and on the different molecules targeting this pathway. First, the authors briefly summarize the immunology of the IL-23/IL-17 pathway to elucidate the mode of action of all different agents. Second, they describe all different molecules targeting this pathway. Besides discussing efficacy and safety data, they also explore immunogenicity, exposure during pregnancy and pharmacokinetics.

Expert opinion: A new era in IBD treatment has recently been initiated: besides immunomodulators and TNF-antagonists, anti-adhesion molecules and monoclonal antibodies targeting the IL-23/IL-17 pathway have been developed. Biomarkers for personalized medicine are urgently needed. This therapeutic (r)evolution will further improve disease-related and patient-reported outcome, though a lot of questions should still be addressed in future years.     

Zalutumumab in head and neck cancer

Introduction: Plaque psoriasis is a chronic inflammatory disease that can result in significant physical, psychological and quality of life impairments. Until recently, biologic treatment for psoriasis was limited to tumor necrosis factor-α inhibitors and an interleukin (IL)-12/23 p40 subunit inhibitor. Newly developed biologics targeting the pro-inflammatory IL-17A cytokine have shown success in providing higher levels of clinical efficacy in patients with psoriasis. Secukinumab, a member of this novel class of IL-17 inhibitors, is the latest biologic to receive US FDA approval for the treatment of moderate-to-severe plaque psoriasis.

Areas covered: This comprehensive review will cover the pharmacology, efficacy, safety and future role of secukinumab and other IL-17 blockers in the treatment of plaque psoriasis.

Expert opinion: While biologics have revolutionized patient care for chronic plaque psoriasis, they are associated with loss of response over time. When treatment failure occurs with existing biologics, physicians are left with few alternative treatment options to offer patients. The introduction of secukinumab has provided an additional therapeutic agent that offers improved skin clearance, better health related quality of life and a favorable side-effect profile.     

A novel electromechanical autoinjector,AutoTouch™, for self-injection of etanercept: real-world use and benefits

Objectives: We assessed the ability of patients with autoimmune inflammatory diseases to successfully use the investigational AutoTouch? reusable autoinjector as well as patient preference for AutoTouch? versus the currently marketed single-use prefilled etanercept SureClick® autoinjector.

Methods: Two multicenter studies were performed: a Home Use Study and a Patient Preference Study. In the Home Use Study, 77 patients with rheumatoid arthritis (RA) or psoriatic arthritis self-administered etanercept once weekly for 5 weeks. The primary end point was successful self-injection of etanercept via AutoTouch?. The Patient Preference Study was an open-label, randomized, 8-week crossover trial (4 weeks for each device) in 216 patients with RA or psoriasis (PsO). The primary end point was preference for AutoTouch? versus SureClick®.

Results: In the Home Use Study, the proportion of successful self-injections with AutoTouch? during weeks 1 through 5 was 97.8% (95% CI, 96.3?99.3). In the Patient Preference Study, patients had a preference rate for AutoTouch? of 41.7% (95% CI, 34.9–48.4) overall, 43.5% (95% CI, 35.5?51.6) for patients with RA, and 36.8% (95% CI, 24.3?49.4) for patients with PsO. Needle apprehension was not different at initiation of the autoinjectors, nor was there a difference between the injectors after 4 weeks. Overall, patients preferred AutoTouch? for ease of self-injecting, ease of pressing the start button, ease of following injection progress, and certainty of knowing when the injection was completed. SureClick® was preferred for fewer steps and experiencing less injection site discomfort or pain.

Conclusion: The introduction of the AutoTouch? will give patients a choice between two different autoinjectors for self-administration of etanercept.     

Effectiveness and safety of secukinumab in Italian patients with psoriasis: an 84 week,multicenter, retrospective real-world study

Background: Long term data on the real-life use of secukinumab are scant. The aim of this study was to investigate the real-life effectiveness, safety and treatment persistence of secukinumab in patients with moderate-to-severe psoriasis.

Research design and methods: This 84-week, multicenter (n = 7) retrospective study analyzed data from patients who initiated and received at least 6 months of secukinumab treatment between June 2016 and June 2018 in the Campania region of Italy. Patient demographic and treatment characteristics, duration of treatment and reasons for discontinuation as well as Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA), and Dermatology Life Quality Index (DLQI) scores were assessed.

Results: 324 patients (63% male, mean age 50.2 years) were enrolled and received a mean 11.7 months of secukinumab treatment. Overall, 9.5% discontinued secukinumab, including 5.2% who discontinued due to secondary inefficacy and 1.8% due to adverse events. PASI, BSA and DLQI scores were significantly improved from baseline at every follow-up visit (p < 0.001) and mean PASI decreased from 15.3 ± 6.3 at baseline to 0.5 ± 1.0 at week 84. Secukinumab had comparable effectiveness in biologic naïve and non-naïve patients.

Conclusions: This study confirmed the effectiveness and safety of secukinumab in real-world patients with psoriasis.     

Positioning ustekinumab in moderate-to-severe ulcerative colitis: new kid on the block

ABSTRACT

Introduction: Ulcerative colitis (UC) is a chronic relapsing disorder of the colonic tract. Dysregulated innate and adaptive immune pathways contribute to intestinal inflammation in IBD, and cytokines, including IL-12 and IL-23, play a key role. The blockade of both IL-12 and IL-23 may have an impact on different pathways of inflammation and could be effective for the treatment of inflammatory bowel diseases.

Ustekinumab is a fully human IgG1κ monoclonal antibody which binds to the shared p40 protein subunit of IL-12 and ?23. It is currently approved for several immune-mediated diseases such as moderate to severe plaque psoriasis, psoriatic arthritis, and Crohn’s disease, and has shown promising results in UC.

Areas covered: A review of the literature was performed to understand several aspects including the role of IL-12 and ?23 in UC, the potential therapeutic role of ustekinumab in inflammatory bowel disease, and the positioning of ustekinumab in the therapeutic algorithm of UC, based on extrapolated data from available randomized clinical trials.

Expert opinion: Ustekinumab is effective and safe in UC, and shows potential advantages compared to other drugs in moderate-to-severe UC.     

Predictors of future exacerbation risk in patients with asthma

Objectives: Although modern treatment of asthma improves asthma control, some patients still experience exacerbations. The aim of the present study was to detect predictors of asthmatic exacerbations

Methods: We included patients with asthma followed up in asthma clinics of 2 tertiary University hospitals. Demographic and functional characteristics, levels of exhaled NO, and inflammatory biomarkers (IL-13, ΕCP και IL-8) and cell counts in induced sputum were recorded at baseline. Measurements were performed with the patients in stability and were considered as their personal best. Patients received optimal treatment with good compliance and were followed up for 1 year for asthma exacerbations occurrence. Evaluation of the effect of recorded parameters on asthma exacerbations was performed with univariate and multivariate Poisson regression analysis.

Results: 171 patients (118 female) with bronchial asthma (mean age 51.6 ± 13.2 years) were included in the study. The mean number of exacerbations in 1 year of follow up was 0.4 ± 0.8 while the majority of patients (71.9%) did not experience any exacerbation. In multivariate Poisson Regression analysis only 3 characteristics were predictors of future exacerbations: FEV₁ [IRR(95% CI)], [0.970(0.954–0.987)], p = 0.001, high BMI [1.078(1.030–1.129)], p = 0.001, and the need for permanent treatment with oral corticosteroids for asthma control maintenance [2.542(1.083–5.964)], p = 0.032

Conclusion: Optimal guideline-based asthma management results in minimal occurrence of exacerbations in the majority of patients. Predictors of exacerbations are low FEV₁ levels in stability, high BMI and the need for permanent treatment with oral corticosteroids.