Cost-Utility Analysis of TNF-α Inhibitors, B Cell Inhibitors, and JAK Inhibitors Versus csDMARDs for Rheumatoid Arthritis Treatment.

INTRODUCTION: Rheumatoid arthritis (RA) is a progressive and debilitating disease, causing persistent joint pain that limits daily activities requiring long-term treatment. Newer targeted therapies expand RA treatment options, but their high cost necessitates a focus on cost effectiveness. To address this, we aim to conduct a cost-utility analysis of these newer RA pharmacotherapies to support evidence-based policy decision-making. METHODS: We analyzed the cost-utility of sequential treatment with TNF-α, B cell and JAK-inhibitors compared with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) for RA treatment in methotrexate (MTX) nonresponders. We used a Markov model with lifetime horizon and 6-month cycles from an Indian health system perspective. Costs (INR 2022) and quality-adjusted life years (QALYs) were used to determine the incremental cost-effectiveness ratios (ICERs) at a cost-effectiveness threshold of India's gross domestic product (GDP) per capita (2022). We assessed uncertainty using univariate, probabilistic sensitivity, and scenario analyses. RESULTS: Despite additional QALYs, TNF-α, B cell, and JAK inhibitors were not cost-effective for treating moderate-to-severe patients with RA unresponsive to csDMARDs (including MTX) in India, as increased costs outweighed their clinical benefits. ICERs ranged from 10,46,206 to 31,09,207 Indian Rupees in the base case analysis, exceeding three times India's GDP per-capita [approximately USD $13,287 to $39,487 and GBP £10,776 to £32,025]. Sensitivity analyses confirmed the results' robustness. Scenario analysis suggested that a cost reduction of over 75% in drug prices could make most of the interventions cost effective compared with csDMARDs. CONCLUSIONS: TNF-α, B cell, and JAK-inhibitors are not cost-effective compared with csDMARDs for patients with RA who have not responded to MTX in India at the current prices. Cost-effectiveness estimates were highly influenced by drug pricing variations. Therefore, reducing the prices of these interventions could enhance affordability, potentially leading to their inclusion in publicly funded health programs.

Outcomes after anti-tumour necrosis factor originator to biosimilar switching in children and young people with juvenile idiopathic arthritis in the UK: a national cohort study.

BACKGROUND: For cost-saving purposes, children and young people with juvenile idiopathic arthritis (JIA) are being switched (for non-medical reasons) from biological originators to biosimilars. Here, we aimed to investigate those who switched from an anti-tumour necrosis factor (TNF) originator to a biosimilar, regarding drug survival and disease activity, compared with a matched cohort who continued the originator. METHODS: This analysis included all patients in the UK JIA Biologics Register switching directly from an anti-TNF originator to a biosimilar of the same product. All patients were matched (age, sex, disease duration, calendar year of when patients started originator therapy, line of therapy, and International League of Associations for Rheumatology [ILAR] category) to patients continuing the originator. For those matched successfully, a Cox proportional hazard model assessed whether drug persistence differed between those who switched compared with those who continued the originator. Overall change in the 71-joint juvenile arthritis disease activity score and the proportion of patients with a clinically important worsening score (by ≥1·7 units) after 6 months was compared between cohorts. This analysis was designed to address a priority research area set by our patient partners. FINDINGS: There were 224 children and young people with non-systemic JIA (139 [62%] were female, and 85 [38%] were male) identified as switching from a biological originator to a biosimilar of the same product from Jan 1, 2017, to July 7, 2023. 143 (64%) patients were originally on adalimumab, 56 (25%) on etanercept, and 25 (11%) on infliximab. Of these, 164 patients were matched successfully to those continuing the originator. There was no evidence that patients switching were more likely to stop treatment compared with those continuing the originator, with a hazard ratio of 1·46 (95% CI 0·93-2·30). Of the 51 patients in the biosimilar group who stopped treatment, 18 (35%) switched back to the originator (14 in the first year), 28 (55%) started a different biological drug, and five (10%) discontinued all treatment by the last follow-up. Of the 87 matched patients with available disease activity, there was no evidence that JADAS-71 worsened more after 6 months, with an odds ratio of 0·71 (95% CI 0·34-1·51; p=0·38). INTERPRETATION: In this matched comparative effectiveness analysis, children and young people with JIA switched from originators to biosimilars. Disease activity was similar between patients switching compared with those continuing the originator. Three quarters of patients were still receiving their biosimilar after 1 year, with switching back to originator uncommon, at only 9% after 1 year, suggesting good tolerability of non-medical switching in this patient population. This information is reassuring to clinicians and patients regarding the effect of non-medical biological switching. FUNDING: British Society for Rheumatology, Versus Arthritis, and National Institutes for Health Research Manchester Biomedical Research Centre.

Enthesitis in a European registry-based cohort of patients with psoriatic arthritis treated with tumour necrosis factor inhibitors: clinical burden, patient-reported outcomes, and treatment response.

OBJECTIVE: To explore the registration of enthesitis among biologic-naïve patients with psoriatic arthritis (PsA) initiating tumour necrosis factor inhibitor (TNFi) treatment across 12 European registries, compare the disease burden and patient-reported outcomes (PROs) between patients with and without enthesitis, and assess the enthesitis treatment response. METHOD: Demographics, clinical characteristics, and PROs at first TNFi (TNFi-1) initiation (baseline) were assessed in patients with PsA, diagnosed by a rheumatologist, with versus without assessment of entheses and between those with versus without enthesitis. Enthesitis scores and resolution frequency were identified at follow-up. RESULTS: Of 10 547 patients in the European Spondyloarthritis (EuroSpA) Research Collaboration Network initiating TNFi, 1357 underwent evaluation for enthesitis. Eight registries included a validated scoring system for enthesitis. At baseline, 874 patients underwent entheses assessment [Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) 485 patients, Spondyloarthritis Research Consortium of Canada (SPARCC) 389 patients]. Enthesitis was detected by MASES in 170/485 (35%, mean score ± sd 3.1 ± 2.4) and by SPARCC in 236/389 (61%, 4 ± 3.4). Achilles enthesitis was most frequent, by both MASES (unilateral/bilateral 28%/9%) and SPARCC (48%/18%). MASES/SPARCC baseline and follow-up scores for TNFi-1 were available for 100/105 patients. Of these, 63 patients (63%) (MASES) and 46 (43.8%) (SPARCC) achieved resolution of enthesitis. The site-specific enthesitis resolution was overall lower at SPARCC sites (peripheral; 63-80%) than at MASES sites (mainly axial; 82-100%) following TNFi-1. Disease activity and PROs were worse in patients with versus without enthesitis. CONCLUSION: Entheseal assessments are only registered in a minority of patients with PsA in routine care. When assessed, enthesitis was common, and a substantial proportion demonstrated resolution following treatment with TNFi-1.

From bench to bedside - is there a role of IL-17 drugs in rheumatoid arthritis?

INTRODUCTION: IL-17 has been described as a pro-inflammatory cytokine that is relevant in the seronegative spondylarthritides with IL-17 targeted therapies being licensed for their treatment.There is evidence to demonstrate that IL-17 is found in RA joints and contributes to the pro-inflammatory cascade. This results in synovial hyperplasia and osteoclastogenesis thus causing joint destruction and bony erosions. AREAS COVERED: This review article summarizes trials that have studied the use of IL-17 targeted therapies in RA patients who have failed conventional synthetic disease-modifying therapy (C-DMARDS) and biologic DMARDS. EXPERT OPINION: The trials that have studied IL-17 inhibitors in RA patients have only shown a modest improvement in disease activity. In several trials, the primary endpoint was not achieved whilst in others, when comparing with existing licensed biologics for RA, did not demonstrate any superiority.Tissue Necrosis Factor-alpha (TNF-α) likely plays more of a pivotal role in the pathogenesis of RA with IL-17 having a synergistic effect. Therefore, in our opinion, IL-17 inhibitors as an independent therapy for RA are less likely to provide a cost-effective benefit. There may be scope to potentially combine it with TNF-α-inhibitors (TNF-i), but this requires further research especially with the potential concerns related to increased immunosuppression.

Quantifying hospital-associated costs, and accompanying travel costs and productivity losses, before and after withdrawing TNF-α inhibitors in juvenile idiopathic arthritis.

OBJECTIVE: To quantify differences in hospital-associated costs, and accompanying travel costs and productivity losses, before and after withdrawing TNF-α inhibitors (TNFi) in JIA patients. METHODS: This was a retrospective analysis of prospectively collected data from electronic medical records of paediatric JIA patients treated with TNFi, which were immediately discontinued, spaced (increased treatment interval) or tapered (reduced subsequent doses). Costs of hospital-associated resource use (consultations, medication, radiology procedures, laboratory testing, procedures under general anaesthesia, hospitalization) and associated travel costs and productivity losses were quantified during clinically inactive disease until TNFi withdrawal (pre-withdrawal period) and compared with costs during the first and second year after withdrawal initiation (first and second year post-withdrawal). RESULTS: Fifty-six patients were included of whom 26 immediately discontinued TNFi, 30 spaced and zero tapered. Mean annual costs were €9165/patient on active treatment (pre-withdrawal) and decreased significantly to €5063/patient (-44.8%) and €6569/patient (-28.3%) in the first and second year post-withdrawal, respectively (P < 0.05). Of these total annual costs, travel costs plus productivity losses were €834/patient, €1180/patient, and €1320/patient in the three periods respectively. Medication comprised 80.7%, 61.5% and 72.4% of total annual costs in the pre-withdrawal, first and second year post-withdrawal period, respectively. CONCLUSION: In the first two years after initiating withdrawal, the total annual costs were decreased compared with the pre-withdrawal period. However, cost reductions were lower in the second year compared with the first year post-withdrawal, primarily due to restarting or intensifying biologics. To support biologic withdrawal decisions, future research should assess the full long-term societal cost impacts, and include all biologics.

Development of a specialty medication clinical dashboard to improve tumor necrosis factor-α inhibitor safety and adherence monitoring.

PURPOSE: To describe the development of a pilot specialty medication clinical dashboard targeting tumor necrosis factor (TNF)-α inhibitor therapy. SUMMARY: This was a quality improvement project conducted between August 2019 and April 2020. The dashboard was designed with collaboration between clinical pharmacists and specialty providers in rheumatology, gastroenterology, and dermatology. Data was queried from the Veterans Affairs Corporate Data Warehouse. Patients with an active prescription or intravenous order for a TNF-α inhibitor were included. Dashboard flag criteria focused on TNF-α inhibitor safety and adherence monitoring. Flag results from the dashboard were characterized from data captured at a single time point. For 431 patients on TNF-α inhibitor treatment at the institution, 304 flags corresponding to 223 unique patients (51.7%) were identified on the dashboard: 3% of patients had a new infection, 9% had overdue monitoring laboratory tests, 5% had a critical laboratory result, 2% were on 2 biologic agents, 27% were overdue for a refill, 6% had an emergency department visit, and 2% had an inpatient admission. No patients were flagged for heart failure exacerbation or new malignancy. Seventeen percent of patients were prescribed high-dose etanercept or adalimumab, representing a potential annual cost savings of $302,497 if 50% of these patients had their dose successfully reduced to labeled dosing. Opportunities for pharmacist intervention utilizing the dashboard were identified and characterized through chart review of flagged patients. CONCLUSION: Pharmacists have the opportunity to improve safety and adherence for TNF-α inhibitor therapy through use of a specialty medication clinical dashboard. The dashboard should be used in conjunction with collaborative practice protocols.

TNF-α: The shape of small molecules to come?

In 2020, the anti-tumor necrosis factor (TNF) monoclonal antibody Humira® generated US$165.8 billion in cumulative sales and snatched the crown for the industry's most successful drug from Lipitor (atorvastatin). TNF-α is a major component in beneficial and disease-related inflammation and TNF-α-inhibitor biologics have gained widespread use in autoimmune diseases, such as rheumatoid arthritis (RA). Many more diseases could benefit from TNF-α inhibitors, such as Alzheimer's disease (AD) or major depression. However, the nature of TNF-α-inhibitor biologics prohibits central nervous system (CNS) applications. Moreover, high drug production costs and pricing, together with antidrug immune reactions and insufficient patient coverage, argue for the development of small-molecule drugs. Recently, drug-like orally available small molecules were described with high activity in animal disease models with activities comparable to those of antibodies.

Eficacia y seguridad de ustekinumab para el tratamiento de pacientes adultos con enfermedad de crohn activa de moderada a severa y falla al tratamiento sistémico convencional e inhibidores del TNF-Alfa / Efficacy and safety of ustekinumab for the treatment of adult patients with moderately to severely active Crohn's disease and failure of conventional systemic treatment and TNF-alpha inhibitors

INTRODUCCIÓN: El presente dictamen expone la evaluación de la eficacia y seguridad de ustekinumab para el tratamiento de pacientes adultos con enfermedad de Crohn activa de moderada a severa y falla al tratamiento sistémico convencional e inhibidores del TNF-alfa. La enfermedad de Crohn (EC) es una enfermedad intestinal, inflamatoria, crónica e infrecuente; asociada a una alta morbilidad y mortalidad. Se estima que la tasa de incidencia es de 3.1 a 20.2 casos por 100,000 personas-año en los Estados Unidos. El tratamiento está dirigido a controlar los síntomas de la EC. La elección de la terapia varía según la ubicación anatómica y la gravedad de la enfermedad. Los fármacos de la terapia sistémica convencional (5-aminosalicilatos, glucocorticoides o inmunomoduladores) se utilizan en los casos leves. En la enfermedad moderada a severa se recomienda el uso de agentes biológicos como inhibidores del TNF-alfa; los cuales se utilizan en monoterapia o en combinación con un agente inmunomodulador. En EsSalud, los pacientes con EC moderada a severa disponen de la terapia sistémica convencional e inhibidores del TNF-alfa (infliximab y adalimumab). Sin embargo, algunos pacientes no responden a estos tratamientos, por lo que reciben solo la mejor terapia de soporte. Esta incluye medicamentos de la terapia convencional, especialmente glucocorticoides. De este modo, los especialistas de la institución señalan que ustekinumab, un anticuerpo anti IL-12 e IL-23, podría ser una alternativa de tratamiento para estos pacientes. METODOLOGÍA: Se llevó a cabo una búsqueda sistemática de la literatura con el objetivo de identificar la mejor evidencia disponible sobre la eficacia y seguridad de ustekinumab para el tratamiento de pacientes adultos con EC activa de moderada a severa y falla al tratamiento sistémico convencional e inhibidores del TNF-alfa. La búsqueda se realizó en las bases de datos: PubMed, The Cochrane Library y LILACS. Adicionalmente, se realizó una búsqueda manual dentro de las páginas web pertenecientes a grupos que realizan evaluación de tecnologías sanitarias (ETS) y guías de práctica clínica (GPC) incluyendo: el National Institute for Health and Care Excellence (NICE), la Canadian Agency for Drugs and Technologies in Health (CADTH), el Scottish Medicines Consortium (SMC), el Scottish Intercollegiate Guidelines Network (SIGN), el Institute for Clinical and Economic Review (ICER), el Institute for Quality and Efficiency in Healthcare (IQWiG por sus siglas en alemán), la Base Regional de Informes de Evaluación de Tecnologías en Salud de las Américas (BRISA), la OMS, el Ministerio de Salud del Perú (MINSA), el Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI), la American Journal of Gastroenterology (ACG), la Canadian Association of Gastroenterology (CAG), y la British Society of Gastroenterology (BSG). Finalmente, se realizó una búsqueda adicional en la página web de registro de ensayos clínicos de ClinicalTrials.gov para identificar ensayos clínicos en curso o con resultados que no hayan sido publicados. RESULTADOS: La presente sinopsis describe la evidencia científica sobre el uso de ustekinumab como tratamiento de pacientes adultos con EC activa de moderada a severa y falla al tratamiento sistémico convencional e inhibidores del TNF-alfa, según el tipo de publicación. CONCLUSIONES: La EC es una enfermedad poco frecuente, por lo tanto, el número de pacientes con EC activa de moderada a severa y falla al tratamiento sistémico convencional e inhibidores del TNF-alfa (población de interés para el presente dictamen) sería aún menor. - En el presente dictamen se evaluó la mejor evidencia científica disponible hasta la actualidad sobre la eficacia y seguridad de ustekinumab para el tratamiento de pacientes adultos con EC activa de moderada a severa y falla al tratamiento sistémico convencional e inhibidores del TNF-alfa. Se identificaron tres GPC desarrolladas por la ACG, la CAG y la BSG; tres ETS desarrolladas por el NICE, el SMC y la CADTH; y un ECA (UNITI-1) presentado en la publicación de Feagan et al. y los resultados de la calidad de vida presentados en la publicación de Sands et al. Las tres GPC recomendaron el uso de ustekinumab como tratamiento de inducción y mantenimiento para los pacientes adultos con EC activa de moderada a severa que fallaron a la terapia convencional o inhibidores del TNF-alfa. Sus recomendaciones se sustentaron en tres ECA: UNITI-1, UNITI-2 e IM-UNITI. No obstante, solo UNITI-1 (fase de inducción) proporciona evidencia específica para la población de interés del presente dictamen. Las tres ETS optaron por recomendar ustekinumab para los pacientes con EC que presentaron falla, recaída o intolerancia a la terapia convencional o a inhibidores del TNF-alfa. Basados en los tres ECA: UNITI-1, UNITI-2 e IM-UNITI, concluyeron que ustekinumab ofrecía un beneficio en la remisión clínica y tenía un perfil de seguridad adecuado; pero, las decisiones finales se dieron en función de los acuerdos de reducción de costos. El ECA UNITI-1, que incluyó a la población de interés del presente dictamen, solo evaluó la fase de inducción con ustekinumab. Se encontró una mayor tasa de remisión clínica (CDAI < 150 puntos) y un perfil de seguridad similar al placebo. Una publicación posterior de UNITI-1 mostró los resultados a favor de ustekinumab en el UNITI-1 sobre la calidad de vida para los puntajes del IBDQ y SF-36 para el componente mental (ambos puntajes definidos como mejoría clínica) representan un posible beneficio adicional; dado que no se han establecido que estos puntos de corte permitan determinar con certeza el beneficio clínico para estos pacientes. En EsSalud, la población de interés no cuenta con alguna alternativa de tratamiento para el control de la enfermedad (vacío terapéutico), por lo tanto, solo recibirían la mejor terapia de soporte (p. ej. con glucocorticoides), que pone en riesgo la seguridad de los pacientes por la elevada incidencia de EA. Asimismo, en caso de optar por la resección quirúrgica como tratamiento paliativo o de emergencia se incrementaría la morbilidad y pondría en riesgo la seguridad de los pacientes. Por lo expuesto, el IETSI aprueba el uso de ustekinumab como tratamiento de inducción para los pacientes con EC activa de moderada a severa y falla al tratamiento sistémico convencional e inhibidores del TNF-alfa. La vigencia del presente dictamen es de un año, según lo establecido en el Anexo N° 1. Así, la continuación de dicha aprobación estará sujeta a la evaluación de los resultados obtenidos y de mayor evidencia que pueda surgir en el tiempo. Asimismo, debido a la escasez de evidencia sobre la eficacia y seguridad del uso de ustekinumab en la fase de mantenimiento, el IETSI no aprueba el uso de ustekinumab como tratamiento de mantenimiento para los pacientes adultos con EC activa de moderada a severa y falla al tratamiento sistémico convencional e inhibidores del TNF-alfa.

Assessment of in vivo bone microarchitecture changes in an anti-TNFα treated psoriatic arthritic patient.

OBJECTIVE: Psoriatic arthritis (PsA) is an inflammatory rheumatic disease, mediated in part by TNFα and associated with bone loss. Anti-TNFα treatment should inhibit this phenomenon and reduce the systemic bone loss. Ultra-high field MRI (UHF MRI) may be used to quantify bone microarchitecture (BM) in-vivo. In this study, we quantified BM using UHF MRI in a PsA patient and followed up the changes related to anti-TNFα treatment. SUBJECTS AND METHODS: A non-treated PsA patient with knee arthritis and 7 gender-matched controls were scanned using a gradient re-echo sequence at UHF MRI. After a year of Adalimumab treatment, the patient underwent a second UHF MRI. A PET-FNa imaging was performed before and after treatment to identify and localize the abnormal metabolic areas. BM was characterized using typical morphological parameters quantified in 32 regions of interest (ROIs) located in the patella, proximal tibia, and distal femur. RESULTS: Before treatment, the BM parameters were statistically different from controls in 24/32 ROIs with differences reaching up to 38%. After treatment, BM parameters were normalized for 15 out of 24 ROIs. The hypermetabolic areas disclosed by PET-FNa before the treatment partly resumed after the treatment. CONCLUSION: Thanks to UHF MRI, we quantified in vivo BM anomalies in a PsA patient and we illustrated a major reversion after one year of treatment. Moreover, BM results highlighted that the abnormalities were not only localized in hypermetabolic regions identified by PET-FNa, suggesting that the bone loss was global and not related to inflammation.

Trends in list prices, net prices, and discounts of self-administered injectable tumor necrosis factor inhibitors.

BACKGROUND: List prices of tumor necrosis factor (TNF) inhibitors drastically increased during the last decade, but previous research has shown that half of these increases were offset by rising manufacturer discounts. It remains unclear to what extent manufacturers' discounts have offset increases in list prices of each self-administered injectable TNF inhibitor. Evaluating trends in net prices and discounts at the product level will be paramount in understanding the role of competition in the biologic market. OBJECTIVES: To (a) describe product-level changes in net prices of each self-administered injectable TNF inhibitor available in 2007-2019 and (b) quantify to what extent manufacturer discounts have offset increases in list prices. METHODS: We obtained 2007-2019 pricing data for etanercept, adalimumab, certolizumab, and golimumab from the investment firm SSR Health, which uses company-reported sales to estimate net prices and discounts for brand products manufactured by publicly traded companies. For each drug and year, we calculated annual costs of treatment for patients with rheumatoid arthritis based on list and net prices and discounts in Medicaid and other payers. RESULTS: From 2007-2019, list prices of etanercept and adalimumab increased by 293% and 295%, respectively; however, discounts offset 47% and 45% of these increases, leading to net price increases of 171% and 203%. List prices of golimumab and certolizumab increased by 183% and 182%, respectively, but with discounts offsetting 58% and 59% of these increases, net prices increased by 103% and 109%. Net prices of golimumab started to decrease after 2016, while net prices of adalimumab and certolizumab experienced their first drop in 2019. Across the study period, discounts in Medicaid and in other payers increased, respectively, from 21% to 85% and 6% to 32% for etanercept; from 26% to 88% and 19% to 35% for adalimumab; from 28% to 63% and 22% to 46% for golimumab; and from 29% to 83% and 27% to 47% for certolizumab. CONCLUSIONS: Despite growing manufacturer discounts, net prices of self-administered injectable TNF inhibitors still increased at a mean annual rate of 9.6% in 2007-2019. This led to net prices tripling for adalimumab and more than doubling for etanercept, golimumab, and certolizumab. DISCLOSURES: This study was funded by the Myers Family Foundation. Hernandez is funded by the National Heart, Lung and Blood Institute (grant number K01HL142847). Funding sources had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. Hernandez has served on Pfizer's scientific advisory board. The other authors have nothing to disclose.

Cost-utility analysis of treatment options after initial tumor necrosis factor inhibitor therapy discontinuation in patients with rheumatoid arthritis.

BACKGROUND: For patients with rheumatoid arthritis (RA) who discontinued initial treatment with tumor necrosis factor inhibitor (TNFi), 2 approaches are commonly used: cycling to another TNFi or switching to a drug with another mechanism of action. Currently, there is no consensus on which approach to use first. A report from the IBM MarketScan Research administrative claims database showed adalimumab (cycling strategy) and abatacept (switching strategy) were more commonly prescribed after the first TNFi discontinuation. OBJECTIVE: To evaluate the cost-utility of adalimumab versus abatacept in patients with RA whose initial TNFi therapy failed. METHODS: A probabilistic cost-utility microsimulation state-transition model was used. Our target population was commercially insured adults with RA, the time horizon was 10 years, and we used a payer perspective. Patients not responding to adalimumab or abatacept were moved to the next drug in a sequence of 3 and, finally, to conventional synthetic therapy. Incremental cost-utility ratios (2016 USD per quality-adjusted-life-year gained [QALY)] were calculated. Utilities were derived from a formula based on the Health Assessment Questionnaire Disability Index and age-adjusted comorbidity score. RESULTS: Switching to abatacept after the first TNFi showed an incremental cost of just more than $11,300 over 10 years and achieved a QALY benefit of 0.16 compared with adalimumab. The incremental cost-effectiveness ratio was $68,950 per QALY. Scenario analysis produced an incremental cost-effectiveness ratio range of $44,573 per QALY to $148,558 per QALY. Probabilistic sensitivity analysis showed that switching to abatacept after TNFi therapy failure had an 80.6% likelihood of being cost-effective at a willingness-to-pay threshold of $100,000 per QALY. CONCLUSIONS: Switching to abatacept is a cost-effective strategy for patients with RA whose discontinue initial therapy with TNFi. DISCLOSURES: Funding for this project was provided by a Rheumatology Research Foundation Investigator Award (principal investigator: Maria A. Lopez-Olivo). Karpes Matusevich's work was supported by a Doctoral Dissertation Research Award from the University of Texas, School of Public Health Office of Research. Lal reports competing interests outside of the submitted work (employed by Optum). Suarez-Almazor reports competing interests outside of the submitted work (consulting fees from Pfizer, AbbVie, Eli Lilly, Agile Therapeutics, Amag Pharmaceuticals, and Gilead). Chan, Swint, and Cantor have nothing to disclose.

Utilization patterns and characteristics of users of biologic anti-inflammatory agents in a large, US commercially insured population.

We report utilization patterns and characteristics of patients treated with biologic anti-inflammatory agents in a large commercially insured patient population in the United States. We identified adult (age ≥18 years) patients receiving biologic anti-inflammatory agents between 1 January 2012 and 31 March 2019 across the five Research Partners in the Biologic and Biosimilars Collective Intelligence Consortium's Distributed Research Network. We examined the number of incident use episodes for each biologic, as well as patient demographic and clinical characteristics. Curated data and analytic tools from the Food and Drug Administration's Sentinel System were used to perform the analyses. We identified 90,360 incident episodes of tumor necrosis factor-alpha inhibitors (TNFi) and 70,506 incident episodes of non-TNFi medications. Adalimumab was the most common TNFi drug (47% of all TNFi episodes) and showed a steady increase in utilization during the study period compared to other TNFi agents. Rituximab was the most commonly initiated non-TNFi medication (44% of non-TNFi episodes). Other non-TNFi agents, namely, ustekinumab, vedolizumab, and secukinumab, demonstrated notable increases in utilization over time. Biosimilar use was limited; we observed 653 incident episodes for infliximab-dyyb and 39 incident episodes for infliximab-abda. As more biologics enter the market, greater variation in the use of biologics with similar indications and between biologic originators and biosimilars is anticipated. Because information on efficacy and safety at the time of drug approval is limited, post-marketing surveillance and research is needed to monitor medication safety and evaluate effectiveness between biologic drugs using real-world data.

Assessment of mustard vesicant lung injury and anti-TNF-α efficacy in rodents using live-animal imaging.

Nitrogen mustard (NM) causes acute lung injury, which progresses to fibrosis. This is associated with a macrophage-dominant inflammatory response and the production of proinflammatory/profibrotic mediators, including tumor necrosis factor alpha (TNF-α). Herein, we refined magnetic resonance imaging (MRI) and computed tomography (CT) imaging methodologies to track the progression of NM-induced lung injury in rodents and assess the efficacy of anti-TNF-α antibody in mitigating toxicity. Anti-TNF-α antibody was administered to rats (15 mg/kg, every 8 days, intravenously) beginning 30 min after treatment with phosphate-buffered saline control or NM (0.125 mg/kg, intratracheally). Animals were imaged by MRI and CT prior to exposure and 1-28 days postexposure. Using MRI, we characterized acute lung injury and fibrosis by quantifying high-signal lung volume, which represents edema, inflammation, and tissue consolidation; these pathologies were found to persist for 28 days following NM exposure. CT scans were used to assess structural components of the lung and to register changes in tissue radiodensities. CT scans showed that in control animals, total lung volume increased with time. Treatment of rats with NM caused loss of lung volume; anti-TNF-α antibody mitigated this decrease. These studies demonstrate that MRI and CT can be used to monitor lung disease and the impact of therapeutic intervention.

Psoriatic arthritis treatment patterns and costs among pharmacologic treatment-naïve patients.

OBJECTIVES: Pharmacologic treatment for psoriatic arthritis (PsA) includes traditional oral small molecules (OSMs), tumor necrosis factor inhibitors (TNFis), and newer oral therapies such as a phosphodiesterase-4 (PDE4) inhibitor and a Janus kinase inhibitor. We aimed to describe treatment patterns and health care costs for treatment-naïve patients with active PsA initiating pharmacologic treatment. STUDY DESIGN: This was an observational, retrospective study. METHODS: We assessed treatment patterns and health care costs from the IBM MarketScan Research databases. We calculated costs during the 12-month follow-up period for inpatient and outpatient medical health care, including outpatient prescription costs. RESULTS: A total of 3491 patients were identified for the study. Incident therapies included OSMs methotrexate (58.3%), sulfasalazine (9.8%), hydroxychloroquine (2.3%), and other OSMs (1.9%); TNFis adalimumab (12.3%), etanercept (8.6%), infliximab (1.9%), and other TNFis (1.4%); and the PDE4 inhibitor apremilast (2.6%). Persistence ranged from 15.2% to 34.6% with OSM monotherapy and from 42.9% to 58.2% with TNFi monotherapy. Percentage of patients with a gap of at least 60 days in therapy ranged from 42.9% to 48.5% with OSMs and from 17.9% to 29.9% with TNFis. Mean first-line unadjusted per-patient per-month total health care costs for OSMs ranged from $1029 to $1456 and mean total health care costs ranged from $19,173 to $25,013. Mean unadjusted per-patient per-month total health care costs for TNFis ranged from $4203 to $7063 and mean total health care costs ranged from $45,635 to $60,933. CONCLUSIONS: Although patients using OSMs had generally lower total health care costs, they also had the highest rates of treatment modifications such as low persistence and medication gaps of at least 60 days.

Assessment of pain and structure after an intra-articular injection of adalimumab in osteoarthritis of the knee: A case report.

INTRODUCTION: Tumor necrosis factor alpha (TNF-α) mediated inflammation has been implicated, in knee osteoarthritis, despite being a predominantly degenerative condition. PATIENT CONCERNS: A 56-year old female, a case of left knee pain not responding to conventional conservative strategies. DIAGNOSIS: A diagnosis of primary osteoarthritis of the left knee, grade 3 osteoarthritis as per the Kellgren-Lawrence Scale was established. INTERVENTIONS: She was administered an intra-articular injection of 10 mg of Adalimumab, a commonly used anti-TNF agent. OUTCOMES: The patient was evaluated at baseline, 1 month, 3 months, and at 6 months. There was a marked improvement in pain intensity (visual analog scale) and quality of life, despite no objective change on the parameters seen on ultrasound of the knee. CONCLUSION: Injection of adalimumab via the intra-articular route into the knee joint in primary osteoarthritis yields promising results.

Laparoscopic ileocaecal resection versus infliximab for terminal ileitis in Crohn's disease: retrospective long-term follow-up of the LIR!C trial.

BACKGROUND: The LIR!C trial showed that laparoscopic ileocaecal resection is a cost-effective treatment that has similar quality-of-life outcomes to treatment with infliximab, an anti-tumour necrosis factor (TNF) drug. We aimed to compare long-term outcomes of both interventions and identify baseline factors associated with the duration of treatment effect in each group. METHODS: In this retrospective follow-up study, we collected data from patients who participated in the LIR!C trial, a multicentre randomised controlled trial that compared quality of life after surgical resection versus infliximab in adult patients with non-stricturing and immunomodulator-refractory ileocaecal Crohn's disease. From Jan 1 to May 1, 2018, we collected follow-up data from the time from enrolment in the LIR!C trial until the last visit at either the gastrointestinal surgeon or gastroenterologist. In this study, outcomes of interest were need for surgery or repeat surgery or anti-TNF therapy, duration of treatment effect, and identification of factors associated with the duration of treatment effect. Duration of treatment effect was defined as the time without need for additional Crohn's disease-related treatment (corticosteroids, immunomodulators, biologics, or surgery). FINDINGS: We collected long-term follow-up data for 134 (94%) of 143 patients included in the LIR!C trial, of whom 69 were in the resection group and 65 were in the infliximab group. Median follow-up was 63·5 months (IQR 39·0-94·5). In the resection group, 18 (26%) of 69 patients started anti-TNF therapy and none required a second resection. 29 (42%) patients in the resection group did not require additional Crohn's disease-related medication, although 14 (48%) of these patients were given prophylactic immunomodulator therapy. In the infliximab group, 31 (48%) of 65 patients had a Crohn's disease-related resection, and the remaining 34 patients maintained, switched, or escalated their anti-TNF therapy. Duration of treatment effect was similar in both groups, with a median time without additional Crohn's disease-related treatment of 33·0 months (95% CI 15·1-50·9) in the resection group and 34·0 months (0·0-69·3) in the infliximab group (log-rank p=0·52). In both groups, therapy with an immunomodulator, in addition to the allocated treatment, was associated with duration of treatment effect (hazard ratio for resection group 0·34 [95% CI 0·16-0·69] and for infliximab group 0·49 [0·26-0·93]). INTERPRETATION: These findings further support laparoscopic ileocaecal resection as a treatment option in patients with Crohn's disease with limited (affected segment ≤40 cm) and predominantly inflammatory terminal ileitis for whom conventional treatment is not successful. FUNDING: None.

TNF-α inhibitors biosimilars as first line systemic treatment for moderate-to-severe chronic plaque psoriasis.

INTRODUCTION: Biologics have revolutionized the therapy of moderate-to-severe plaque psoriasis. Despite their greater efficacy over conventional systemic therapies their high cost has represented a burden for health-care systems, which limited their use. The availability of biosimilars at low cost is changing the place in therapy of biologics for psoriasis. AREAS COVERED: The role of TNF- α inhibitors in the management of plaque psoriasis, their efficacy and safety profile are presented. Phase 3 clinical trials and real-life data from the use of TNF- α inhibitor biosimilars in the treatment of plaque psoriasis are also reviewed in detail. Furthermore, arguments in favor of the use of TNF- α inhibitor biosimilars as a first-line therapy in moderate-to-severe plaque psoriasis are discussed. EXPERT OPINION: An increasing amount of data show that biosimilars represent a safe and effective alternative to the originator biologics. In the face of ever-increasing health-care costs, switching to biosimilars and starting naïve patients on the best-value biologic can reduce expenditure for patients and payers while maintaining a high-quality care. Moreover, as the cost of biosimilars is approaching the cost of conventional systemic treatments, TNF-α inhibitors biosimilars may represent a first-line systemic treatment for psoriasis patients because they are effective and safe.