Market Access Analysis of Biologics and Small-Molecule Inhibitors for Inflammatory Bowel Disease Among US Health Insurance Policies.

BACKGROUND AND AIMS:Treatment pathways for ulcerative colitis (UC) and Crohn's disease (CD) are shifting to a more individualized, risk-stratified approach. The perception is that insurance policies may not have implemented this paradigm shift, particularly regarding access to newer agents. We evaluated patient access to advanced therapies by analyzing policy information from the Managed Markets Insight and Technology database. METHODS:Coverage status as of December 2018 for all US lives was queried for adalimumab, infliximab, infliximab-dyyb, tofacitinib, ustekinumab, and vedolizumab by indication (UC and/or CD) and medical or pharmacy coverage benefit. Coverage status was classified by the number of biologic steps before access to specified drug as "No Biologic," "1 Prior Biologic," "2+ Prior Biologics," "Not Covered." Unknown lives were excluded from the analyses. RESULTS:Coverage analysis was available for approximately 302 million lives under each medical and pharmacy benefit. Our analysis indicates that approximately half of covered lives had access to all agents (except tofacitinib) as first-line therapy; two-thirds had access after one biologic exposure. Among newer agents, vedolizumab had the widest coverage. For indications of UC and CD, 81% of known lives had access to vedolizumab with no prior biologic exposure required ("No Biologic"), 95% after "No Biologic" + "1 prior Biologic." Geographic variations were identified for coverage patterns. CONCLUSIONS:This US-based healthcare policy analysis points to an increased access to advanced therapies for UC and CD. An individualized, risk-stratified treatment approach integrating advanced therapies, including those recently approved, into treatment pathways for UC and CD is feasible

A systematic review of cost-effectiveness studies comparing conventional, biological and surgical interventions for inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic disease placing a large health and economic burden on health systems worldwide. The treatment landscape is complex with multiple strategies to induce and maintain remission while avoiding long-term complications. The extent to which rising treatment costs, due to expensive biologic agents, are offset by improved outcomes and fewer hospitalisations and surgeries needs to be evaluated. This systematic review aimed to assess the cost-effectiveness of treatment strategies for IBD. A systematic literature search was performed in March 2017 to identify economic evaluations of pharmacological and surgical interventions, for adults diagnosed with Crohn's disease (CD) or ulcerative colitis (UC). Costs and incremental cost-effectiveness ratios (ICERs) were adjusted to reflect 2015 purchasing power parity (PPP). Risk of bias assessments and a narrative synthesis of individual study findings are presented. Forty-nine articles were included; 24 on CD and 25 on UC. Infliximab and adalimumab induction and maintenance treatments were cost-effective compared to standard care in patients with moderate or severe CD; however, in patients with conventional-drug refractory CD, fistulising CD and for maintenance of surgically-induced remission ICERs were above acceptable cost-effectiveness thresholds. In mild UC, induction of remission using high dose mesalazine was dominant compared to standard dose. In UC refractory to conventional treatments, infliximab and adalimumab induction and maintenance treatment were not cost-effective compared to standard care; however, ICERs for treatment with vedolizumab and surgery were favourable. We found that, in general, while biologic agents helped improve outcomes, they incurred high costs and therefore were not cost-effective, particularly for use as maintenance therapy. The cost-effectiveness of biologic agents may improve as market prices fall and with the introduction of biosimilars. Future research should identify optimal treatment strategies reflecting routine clinical practice, incorporate indirect costs and evaluate lifetime costs and benefits

ECCO Topical Review on Biological Treatment Cycles in Crohn’s Disease

There are now a growing number of licensed biological therapies for patients with Crohn’s disease. However, there can be significant costs associated with long-term maintenance treatment, as well as some concerns about potential side-effects. As a result, there has been increasing interest in elective biological treatment discontinuation in selected patients, after a sustained period of remission. Following discontinuation, in cases of relapse, evidence to date has suggested that remission may often be regained by re-treatment with the same biological agent. Therefore, a concept has emerged in which cycles of biological therapy might be used. If this treatment strategy were to be applied in a subgroup of patients at low risk of relapse, cycling might allow a substantial number of patients to have a lower, overall therapeutic burden—ensuring decreased exposure to biological therapy but still enabling appropriate disease control.Currently, there remains uncertainty about the benefit–risk balance for using cycles of biological treatment for patients with Crohn’s disease. Accordingly, an expert panel was convened by the European Crohn’s and Colitis Organisation [ECCO] to review the published literature and agree a series of consensus practice points. The panel aimed to provide evidence-based guidance on multiple aspects of biological treatment discontinuation and cycling, including the risk of relapse after elective treatment discontinuation, predictors of probable relapse or remission, safety, patient preferences, and pharmacoeconomic aspects. Crucially, discussions about biological treatment discontinuation and cycling should be individualized, to enable shared decision-making by patients with their clinicians

Challenges in Therapeutic Drug Monitoring: Optimizing Biological Treatments in Patients With Inflammatory Bowel Disease and Other Immune-Mediated Inflammatory Diseases

Background: Therapeutic drug monitoring (TDM) is a decision-making tool for optimizing the use of certain therapies. In this article, the authors review the role of proactive TDM of biological agents in patients with inflammatory bowel disease (IBD) and other immune-mediated inflammatory diseases (IMID). They also discuss the future of TDM as a component of personalized medicine from the clinical laboratory perspective. Methods: This narrative review originated from proceedings of the fifth biannual Challenges in Therapeutic Drug Monitoring seminar and was supplemented by additional literature identified at various stages of critical review. Results: Proactive TDM aims to achieve adequate concentrations of biological drugs, such that patients attain and maintain an optimal treatment response. Proactive TDM may also have a role in de-escalating anti-tumor necrosis factor therapy in patients in clinical remission and in optimizing infliximab monotherapy as an alternative to combination therapy with an immunomodulator. A major proactive TDM application is in pediatric patients with IBD. Achieving mucosal healing in children with IBD requires that infliximab or adalimumab concentrations are monitored early during induction therapy, with dose modifications guided by the timing (week) of measurement. Recent innovations in biological therapy include international standards for infliximab and adalimumab for the global harmonization of bioactivity and monotest devices with an accuracy equivalent to that of conventional enzyme-linked immunosorbent assays and quicker turnaround times. Conclusions: Despite several knowledge gaps regarding proactive TDM of anti-tumor necrosis factor therapy in patients with IMID, growing evidence suggests that it is associated with better outcomes than empiric optimization and/or reactive TDM in IBD. Enhanced pharmacokinetic modeling to predict drug exposure and patient genotyping for the precise application of proactive TDM are considered key elements to optimize biological therapy in the future

Treatment of psoriasis with biologic agents in Malta

Introduction: Biologic therapy has revolutionalised the treatment of moderate to severe psoriasis leading to improved clinical outcomes and quality of life scores. This study aims to determine current biologic use in psoriatic patients at our Dermatology department at Sir Paul Boffa hospital, Malta. Method: All patients who were administered biologic therapy for psoriasis in Malta until the end of 2014 were included. Data included demographic details, disease duration and severity, biologic use and duration, previously attempted treatments, side effects, early and late response to biologic using Psoriasis Area Severity Index (PASI) scores and Dermatology Life Quality index (DLQI) scores. Results: A total of 36 patients were started on a biologic between 2009 and 2014 for psoriasis (M:25, F:11) with a mean age of 46.9 years. These included etanercept (n=22), infliximab (n=8), adalimumab (n=4) and ustekinumab (n=2). Secondary failure was the main reason why biologics were stopped and switched. Most patients had an improvement in their PASI scores after 2 to 4 weeks of starting the biologic and had a PASI 90 score improvement. All patients had more than a 5 point improvement in DLQI score. Discussion: Biologic use in our department is on the increase. Our patients had considerable improvements in their PASI and DLQI scores. Secondary failures have occurred usually after 2 to 4 years and switching has yielded positive results. Biologics are expensive drugs and recently we have switched to cheaper biosimilars. Doctors should be aware of the treatment options available for psoriasis patients, their possible side effects and when to refer to our department. In most cases a satisfactory response can be achieved.peer-reviewe

Cost-Effectiveness of Therapeutic Drug Monitoring of Anti-TNF Therapy in Inflammatory Bowel Disease: A Systematic Review

Infliximab and adalimumab are monoclonal antibodies against tumor necrosis factor (anti-TNF) used to manage inflammatory bowel disease (IBD). Therapeutic Drug Monitoring (TDM) has been proven to prevent immunogenicity, to achieve better long-term clinical results and to save costs in IBD treatment. The aim of this study was to conduct a systematic review on cost-effectiveness analyses of studies that apply TDM of anti-TNF in IBD and to provide a critical analysis of the best scientific knowledge available in the literature. The quality of the included studies was assessed using Consolidated Health Economic Evaluation Reporting Standards (CHEERS). Cost-effectiveness of the TDM strategies was presented as total costs, cost savings, quality-adjusted life-years (QALY) and incremental cost-effectiveness ratio (ICER). Thirteen studies that examined the health economics of TDM of anti-TNF in IBD from 2013 to 2021 were included. Eight of them (61.5%) achieved a score between 17 and 23 on the CHEERS checklist. The comparison between the TDM strategy and an empirical strategy was cost saving. The ICER between reactive TDM and an empirical strategy was dominated (favorable) by reactive TDM, whereas the ICER value for proactive TDM compared to an empirical strategy ranged from EUR 56,845 to 3,901,554. This systematic review demonstrated that a TDM strategy is cost-effective or cost-saving in IBD.S.M.-M. received a predoctoral fellowship from Miguel Hernandez University (“Ayudas a la contratación de personal investigador en formación 2021”).S

Enhancing treatment success in inflammatory bowel disease: Optimising the use of anti-TNF agents and utilising their biosimilars in clinical practice.

Abstract Anti-tumour necrosis factor (TNF) agents such as infliximab and adalimumab have greatly altered the treatment landscape in inflammatory bowel disease (IBD). However, there are remaining unmet needs and opportunities to optimise their use. Recent data suggest that proactive therapeutic drug monitoring may lead to more efficient usage of these agents, with potential for higher rates of corticosteroid-free clinical remission than with reactive monitoring. Expanded application of faecal calprotectin measurements may also be valuable, given the ease of use of the assay and its proven effectiveness as a diagnostic tool and predictor of relapse risk. From a practical viewpoint, improved multidisciplinary working may be essential to optimise patient care, with IBD nurse specialists playing an increasingly central role within this model. Finally, the availability of biosimilars of the anti-TNF agents allow drug costs to be reduced without compromising safety or efficacy – thereby providing opportunities to improve accessibility. Alongside extensive data on originator to biosimilar infliximab switch, new studies are beginning to demonstrate the safety of biosimilar to biosimilar switch, as well as adalimumab biosimilar transitions. The risk of a nocebo effect when switching to a biosimilar can be reduced through improved patient education and preparation

Anti‑TNF agents and new biological agents (Vedolizumab and Ustekinumab) in the prevention and treatment of postoperative recurrence after surgery in crohn’s disease

Surgery for Crohn’s disease (CD) is not curative, as postoperative recurrence (POR) after ileocolonic resection is the rule in the absence of prophylactic treatment. In the present article, we critically review available data on the role of anti-tumour necrosis factor (TNF) agents and new biologics (including vedolizumab and ustekinumab) in the prevention and treatment of POR after surgery in CD. Several studies (summarised in various meta-analyses) have confrmed the efcacy of anti-TNFs in the prevention of POR. We identifed 37 studies, including 1863 CD patients, with mean endoscopic POR at 6–12 months of 29%. Only few randomised controlled trials (RCTs) have directly compared thiopurines and anti-TNFs, with controversial results, although the superiority of the latter is supported by several meta-analyses. Infiximab and adalimumab seem equally efective. The combination of anti-TNFs and immunosuppressives should be considered in patients previously exposed to anti-TNFs. Several studies have shown that anti-TNFs remain an efective option to prevent POR also in patients with anti-TNF failure before surgery. In fact, the use of the same anti-TNF before and after surgery might be efective for the prevention of POR. Prophylactic anti-TNF treatment, once started, should be continued long term. Anti-TNFs are also efective for the treatment of established POR. Retreatment with anti-TNFs for POR is a valid strategy even after their preoperative failure. In six studies (including 156 patients) evaluating vedolizumab, mean endoscopic POR at 6–12 months was 41%. The non-randomised comparison of anti-TNFs and vedolizumab has provided controversial results. One placebo-controlled RCT confrmed that vedolizumab is quite efective in preventing POR in CD patients with increased risk of recurrence. Seven studies (including 162 patients) evaluated ustekinumab, with a mean endoscopic POR at 6–12 months of 41%. The comparative efcacy of ustekinumab and anti-TNFs is still unclear. Ustekinumab and vedolizumab seem to be equally efective, although the experience is very limited. In conclusion, to date, anti-TNFs are the most efective agents in preventing and treating POR in CD. Anti-TNFs remain an efective option to prevent POR also in patients with anti-TNF failure before surgery. Vedolizumab seems to be quite efective in the prevention of POR in patients with increased risk of recurrence. Ustekinumab is probably also efective in the postoperative setting, although the comparative efcacy with anti-TNFs or vedolizumab is still unclea

Lengthening adalimumab dosing interval in quiescent Crohn's disease patients: Protocol for the pragmatic randomised non-inferiority LADI study

Introduction Adalimumab is effective for maintenance of remission in patients with Crohn's disease (CD) at a dose of 40 mg subcutaneously every 2 weeks. However, adalimumab is associated with (long-term) adverse events and is costly. The aim of this study is to demonstrate non-inferiority and cost-effectiveness of disease activity guided adalimumab interval lengthening compared to standard dosing of every other week (EOW). Methods and analysis The Lengthening Adalimumab Dosing Interval (LADI) study is a pragmatic, multicentre, open label, randomised controlled non-inferiority trial. Non-inferiority is reached if the difference in cumulative incidence of persistent (>8 weeks) flares does not exceed the non-inferiority margin of 15%. 174 CD patients on adalimumab maintenance therapy in long-term (>9 months) clinical and biochemical remission will be included (C-reactive protein (CRP) 250 μg/g, CRP≥10 mg/l, HBI≥5. Secondary outcomes include cumulative incidence of transient flares, adverse events, predictors for successful dose reduction and cost-effectiveness. Ethics and dissemination The study is approved by the Medical Ethics Committee Arnhem-Nijmegen, the Netherlands (registration number NL58948.091.16). Results will be published in peer-reviewed journals and presented at international conferences. Trial registration numbers EudraCT registry (2016-003321-42); Clinicaltrials.gov registry (NCT03172377); Dutch trial registry (NTRID6417)