Real-world clinical outcomes and healthcare costs in patients with Crohn's disease treated with vedolizumab versus ustekinumab in the United States.

OBJECTIVE: To compare real-world treatment persistence, dose escalation, rates of opportunistic or serious infections, and healthcare costs in patients with Crohn's disease (CD) receiving vedolizumab (VDZ) vs ustekinumab (UST) in the United States. METHODS: A retrospective observational study in adults with CD initiated on VDZ or UST on/after 26 September 2016, was performed using the IBM Truven Health MarketScan databases (1 January 2009-30 September 2018). Rates of treatment persistence, dose escalation, opportunistic or serious infection-related encounters, and healthcare costs per patient per month (PPPM) were evaluated. Entropy balancing was used to balance patient characteristics between cohorts. Event rates were assessed using weighted Kaplan-Meier analyses and compared between cohorts using log-rank tests. Healthcare costs were compared between cohorts using weighted 2-part models. RESULTS: 589 VDZ and 599 UST patients were included (172 [29.2%] and 117 [19.5%] were bio-naïve, respectively). After weighting, baseline characteristics were comparable between cohorts. No significant difference in rates of treatment persistence (12-month: VDZ, 76.5%; UST, 82.1%; p = .17), dose escalation (12-month: VDZ, 29.3%; UST, 32.7%; p = .97), or opportunistic or serious infection-related encounters were observed between VDZ and UST. Total mean healthcare costs were significantly lower for patients treated with VDZ vs UST (mean cost difference = -$5051 PPPM; p < .01). Findings were consistent in bio-naïve patients. CONCLUSIONS: In this real-world study, similar treatment persistence, dose escalation, and rates of opportunistic or serious infections were observed with VDZ- and UST-treated patients with CD. However, VDZ was associated with a significantly lower cost outlay for healthcare systems.

Crohn's disease (CD) causes inflammation in the digestive system. Vedolizumab (VDZ) and ustekinumab (UST) are therapies for patients with CD. Little is known about the clinical outcomes and healthcare costs of VDZ versus UST in the real world in the United States. We used health claims data and found that VDZ and UST had comparable real-world clinical outcomes. After 12 months of treatment, the proportions of patients with CD who stayed on treatment and those who needed to increase therapy dose were similar with VDZ and UST. The rate of infection was also similar between the two groups of patients. However, the monthly healthcare costs were $5051 less for patients treated with VDZ than with UST. This was mainly due to the lower cost of VDZ, which was almost half of that of UST. The lower treatment costs with VDZ may provide substantial savings for the healthcare system and patients specifically. Future cost-effectiveness studies on VDZ and UST are needed to aid treatment selection for patients with CD.

Risk of serious infection associated with different classes of targeted therapies used in psoriatic arthritis: a nationwide cohort study from the French Health Insurance Database (SNDS).

OBJECTIVE: To assess the risk of serious infection associated with different targeted therapies for psoriatic arthritis (PsA) in real-world settings. METHODS: This nationwide cohort study used the administrative healthcare database of the French health insurance scheme linked to the hospital discharge database to identify all adults with PsA who were new users of targeted therapies (adalimumab, etanercept, golimumab, certolizumab pegol, infliximab, secukinumab, ixekizumab, ustekinumab, and tofacitinib) from 1 January 2015 to 30 June 2021. The primary outcome was a serious infection (ie, requiring hospitalisation), in a time-to-event analysis using propensity score-weighted Cox models, with adalimumab as the comparator, estimating weighted HRs (wHRs) and their 95% CIs. RESULTS: A total of 12 071 patients were included (mean age 48.7±12.7 years; 6965 (57.7%) women). We identified 367 serious infections (3.0% of patients), with a crude incidence rate of 17.0 per 1000 person-years (95% CI, 15.2 to 18.7). After inverse propensity score weighting and adjustment for time-dependent covariates and calendar year, risk of serious infection was significantly lower for new users of etanercept (wHR 0.72; 95% CI, 0.53 to 0.97) or ustekinumab (wHR, 0.57; 95% CI, 0.35 to 0.93) than adalimumab new users. This risk was not statistically modified with the other targeted therapies. CONCLUSIONS: The incidence of serious infection was low for PsA patients who were new users of targeted therapies in real-world settings. Relative to adalimumab new users, this risk was lower among new users of etanercept and ustekinumab and unmodified for the other molecules.

Higher Ustekinumab Levels in Maintenance Therapy are Associated with Greater Mucosal Healing and Mucosal Response in Crohn's Disease: An Experience of 2 IBD Centers.

BACKGROUND: Ustekinumab (UST), a human monoclonal antibody that binds the p40 subunit of interleukin 12 (IL-12) and IL-23, is licensed for induction and maintenance therapy of moderate to severe inflammatory bowel disease (IBD). To date, there is limited data published on any potential association between ustekinumab serum trough levels and mucosal healing in order to guide treatment strategies and appropriate dosing. AIM: This study aims to identify a relationship between maintenance ustekinumab serum trough levels and mucosal healing and/or response in patients with Crohn's disease in an observational cohort study. METHODS: Ustekinumab serum trough levels and antibody titres were analyzed in patients on maintenance drug using an ELISA drug-tolerant assay. Mucosal response (MR) was defined as ≥50% reduction in fecal calprotectin level (FC) and/or ≥50% reduction in the Simple Endoscopic Score for Crohn's Disease (SES-CD score). Mucosal healing (MH) was defined as FC ≤150 µg/mL and/or global SES-CD score ≤5. Median trough levels were analyzed using the Kruskal-Wallis test, and logistic regression was used to determine sensitivity and specificity of levels predicting mucosal response. RESULTS: Forty-seven patients on maintenance ustekinumab for Crohn's disease were included in this study. The majority were female (66%), with a median age of 40 years (21-78 years). The majority of patients were biologic-experienced (89.4%, n = 42). Patients with histologically confirmed Crohn's disease represented 100% (n = 47) of the cohort. Over one-third of patients (n = 18, 38.3%) were on higher than standard dosing of 90 mg every 8 weeks. Patients with mucosal healing (n = 30) had significantly higher mean serum ustekinumab levels (5.7 µg/mL, SD 6.4) compared with those with no response (1.1 µg/mL, SD 0.52; n = 7, P < .0001). A serum ustekinumab trough level greater than 2.3 µg/mL was associated with MH, with a sensitivity of 100% and specificity of 90.6% (likelihood ratio 10.7). Similarly, for patients with MR (n = 40), we observed a higher mean serum ustekinumab trough level (5.1 µg/mL, SD 6.1) compared with those with no response (1.1 µg/mL, SD 0.52; n = 7, P < .0001). Furthermore, a serum ustekinumab trough level greater than 2.3 µg/mL was associated with a 10-fold increased likelihood of mucosal response vs mucosal nonresponse (sensitivity 100%, specificity 90.5%, likelihood ratio 10.5). CONCLUSION: This study demonstrates that higher ustekinumab serum trough levels are associated with a greater likelihood of achieving mucosal healing and mucosal response in patients with Crohn's disease regardless of prior biologic exposure. Further prospective studies are required to correlate target maintenance trough levels and the optimal time to dose-escalate in order to improve patient outcomes.

An indirect comparison of efficacy including histologic assessment and safety in biologic therapy in ulcerative colitis: Systemic review and network meta-analysis.

BACKGROUNDS AND AIMS: There are currently no studies comparing histologic remission of FDA-approved biologics for moderate to severe ulcerative colitis (UC), except for one head-to-head VARSITY trial. The current study employs a network meta-analysis to compare the efficacy, including histologic remission and safety of biologic agents for UC. METHODS: Using four electronic databases, including Pubmed, EMBASE, The Cochrane Library, and ClinicalTrials.gov, a search was conducted of all literature published until September 2022. Included were studies of randomized controlled trials with adult patients with moderate to severe UC using biologics approved by the FDA. An odd ratio with a 95 percent credible interval and ranking information was calculated for each endpoint. RESULTS: The results of the network meta-analysis did not reveal statistically significant differences among biological agents. However, the ranking information for each biological agent exhibited the following patterns. Vedolizumab was ranked first for overall efficacy endpoints in the maintenance phase, including histologic remission. Except for histologic remission, Ustekinumab was identified as the top-ranked drug for induction phase efficacy endpoints other than histologic remission. Adalimumab was identified as the top-ranked drug for maintenance phase corticosteroid-free remission. Vedolizumab was identified as the top-ranked drug in the induction phase for Treatment Emergent Adverse Events (TEAE). Adalimumab was identified as the top-ranked drug in the induction phase for infection. For TEAE and infection in the maintenance phase and Treatment Emergent Severe Adverse Events (TESAE) in both the induction and maintenance phases, Ustekinumab was determined to be the top-ranked medication. CONCLUSIONS: Including histologic remission, for the overall efficacy endpoints in the maintenance phase, VDZ was identified as the first rank drug, but there was no statistically significant difference between biologics. Therefore, the generalization of the results of this study is bounded due to the intrinsic limitations of the study provided.

Cost per responder of biologic drugs used in the treatment of moderate-to-severe plaque psoriasis in France and Germany.

OBJECTIVE: The treatment of moderate-to-severe plaque psoriasis has seen significant improvements in recent years with the advent of biologic drugs. The aim of this study was to assess the cost-effectiveness of anti-IL17 drugs and other biologic therapies used to treat moderate-to-severe plaque psoriasis in France and Germany over a one-year time horizon. METHODS: We developed a cost per responder model for biologic drugs used in psoriasis treatment. The model included anti-IL17s (brodalumab, secukinumab, ixekizumab and bimekizumab), anti-TNFs (adalimumab, etanercept, certolizumab and infliximab), an anti-IL12/23 (ustekinumab), and anti-IL23s (risankizumab, guselkumab and tildrakizumab). Efficacy estimates were collected through a systematic literature review of network meta-analyses on long-term Psoriasis Area and Severity Index (PASI) measures. Dose recommendations and country-specific prices were used to calculate drug costs. Biosimilar drug prices were used when available as a substitute for the originator drugs. RESULTS: After one year, brodalumab had the lowest cost per PASI100-responder in both France (€20,220) and Germany (€26,807) across all available biologic treatments. Among the anti-IL17s, brodalumab had a 23% lower cost per PASI100-responder vs. the nearest comparator in France (bimekizumab, €26,369), and 30% lower vs. nearest comparator in Germany (ixekizumab, €38,027). Brodalumab also had the lowest cost per PASI75- and PASI90-responder among the anti-IL17s in both France and Germany after one year. Adalimumab had the lowest cost per PASI100-responder among the anti-TNFs in both France (€23,418) and Germany (€38,264). Among the anti-IL-23s, risankizumab had the lowest cost per PASI100-responder in both France (€20,969) and Germany (€26,994). CONCLUSION: Driven by its lower costs and high response rates, brodalumab was the most cost-effective treatment option for moderate-to-severe plaque psoriasis over a one-year time-horizon within the anti-IL17 class and when compared to all other biologics in France and Germany.

A retrospective analysis of treatment patterns, drug discontinuation and healthcare costs in Crohn's disease patients treated with biologics.

BACKGROUND/AIMS: This real-world analysis evaluated the persistence and direct healthcare costs of Crohn's Disease (CD) patients treated with biologics in Italy. METHODS: A retrospective analysis on administrative databases of Italian healthcare entities, covering 10.4 million residents, was performed. Adult CD patients under biologics between 2015 and 2020 were included and attributed to first/second treatment line based on absence/presence of biologic prescriptions 5-years before index-date (first biologic prescription). RESULTS: Of 16,374 CD patients identified, 1,398 (8.5%) were biologic-treated: 1,256 (89.8%) in first line and 135 (9.7%) in second line. Kaplan-Meier curves estimated a higher persistence for ustekinumab-treated patients followed by vedolizumab, infliximab and adalimumab, in both lines. Considering baseline variables and adalimumab as reference, infliximab in first line (HR: 0.537) and ustekinumab in first (HR: 0.057) and second line (HR: 0.213) were associated with significantly reduced risk of drug-discontinuation. First line total/average healthcare direct-costs were €13,637, €11,201, €17,104 and €18,340 in patients persistent on adalimumab, infliximab, ustekinumab and vedolizumab, respectively. CONCLUSIONS: This real-world analysis showed differences in persistence over 12-months between biologic treatments, being higher in ustekinumab-treated group, followed by vedolizumab, infliximab and adalimumab. Patients' management was associated with comparable direct healthcare costs among treatment lines, mainly driven by drug-related expenses.

Cost-Effectiveness Analysis of Tofacitinib Compared with Biologics in Biologic-Naïve Patients with Moderate-to-Severe Ulcerative Colitis in Japan.

OBJECTIVE: Tofacitinib is an oral Janus kinase inhibitor approved for the treatment of ulcerative colitis (UC). The objective of this study was to evaluate the long-term cost-effectiveness of tofacitinib versus current biologics, considering combinations of first-line (1L) and second-line (2L) therapies, from a Japanese payer's perspective in patients with moderate-to-severe active UC following an inadequate response to conventional therapy and in those who were naïve to biologics. METHODS: A cost-effectiveness analysis was conducted during the time horizon specified in the Markov model, which considers a patient's lifetime as 60 years and an annual discount rate of 2% on costs and effects. The model compared tofacitinib with vedolizumab, infliximab, adalimumab, golimumab, and ustekinumab. The time of active treatment was divided into induction and maintenance phases. Patients not responding to their biologic treatment after induction or during the maintenance phase were switched to a subsequent line of therapy. Treatment response and remission probabilities (for induction and maintenance phases) were obtained through a systematic literature review and a network meta-analysis that employed a multinomial analysis with fixed effects. Patient characteristics were sourced from the OCTAVE Induction trials. Mean utilities associated with UC health states and adverse events (AEs) were obtained from published sources. Direct medical costs related to drug acquisition, administration, surgery, patient management, and AEs were derived from the JMDC database analysis, which corresponded with the medical procedure fees from 2021. The drug prices were adjusted to April 2021. Further validation through all processes by clinical experts in Japan was conducted to fit the costs to real-world practices. Scenario and sensitivity analyses were also performed to confirm the accuracy and robustness of the base-case results. RESULTS: In the base-case, the treatment pattern including 1L tofacitinib was more cost-effective than vedolizumab, infliximab, golimumab, and ustekinumab for 1L therapies in terms of cost per quality-adjusted life year (QALY) gained (based on the Japanese threshold of 5,000,000 yen/QALY [38,023 United States dollars {USD}/QALY]). The base-case results demonstrated that the incremental costs would be reduced for all biologics, and decreases in incremental QALYs were observed for all biologics other than adalimumab. The incremental cost-effectiveness ratio (ICER) was found to be dominant for adalimumab; for the other biologics, it was found to be less costly and less efficacious. The efficiency frontier on the cost-effectiveness plane indicated that tofacitinib-infliximab and infliximab-tofacitinib were more cost-effective than the other treatment patterns. When infliximab-tofacitinib was compared with tofacitinib-infliximab, the ICER was 282,609,856 yen/QALY (2,149,157 USD/QALY) and the net monetary benefit (NMB) was -12,741,342 yen (-96,894 USD) with a threshold of 5,000,000 yen (38,023 USD) in Japan. Therefore, infliximab-tofacitinib was not acceptable by this threshold, and tofacitinib-infliximab was the cost-effective treatment pattern. CONCLUSION: The current analysis suggests that the treatment pattern including 1L tofacitinib is a cost-effective alternative to the biologics for patients with moderate-to-severe UC from a Japanese payer's perspective.

Illustrating Emerging Good Practices for Quantitative Benefit-Risk Assessment: A Hypothetical Case Study of Systemic Biologic Treatments for Plaque Psoriasis.

OBJECTIVES: Quantitative benefit-risk assessment (qBRA) is a structured process to evaluate the benefit-risk balance of treatment options to support decision making. The ISPOR qBRA Task Force was recently established to provide recommendations for the design, conduct, and reporting of qBRA. This report presents a hypothetical case study illustrating how to apply the Task Force's recommendations toward a qBRA to inform the benefit-risk assessment of brodalumab at the time of initial marketing approval. The qBRA evaluated 2 dosing regimens of brodalumab (210 mg or 140 mg twice weekly) compared with weight-based dosing of ustekinumab and placebo. METHODS: We followed the 5 steps recommended by the Task Force. Attributes included treatment response (≥75% improvement in Psoriasis Area and Severity Index), suicidal ideation and behavior, and infections. Performance data were drawn from pivotal clinical trials of brodalumab. The qBRA used multicriteria decision analysis and preference weights from a hypothetical discrete choice experiment. Sensitivity analyses examined the robustness of benefit-risk ranking to uncertainty in clinical effect and preference estimates, consideration of a subgroup (nail psoriasis), and the maintenance phase of treatment (52 weeks instead of 12). RESULTS: Results from this hypothetical qBRA suggest that brodalumab 210 mg had a more favorable benefit-risk profile compared with ustekinumab and placebo. Ranking of brodalumab compared with ustekinumab was dependent on brodalumab's dose. Sensitivity analyses demonstrated robustness of benefit-risk ranking to uncertainty in clinical effect and preference estimates, as well as choice of attributes and length of follow-up. CONCLUSION: This case study demonstrates how to implement the ISPOR Task Force's good practice recommendations on qBRA.

Real-world dose adjustments of biologic treatments in psoriasis and their economic impact: a Swedish national population study.

BACKGROUND: To date, evidence on the dose adjustments of biologics in the real-world treatment of psoriasis is limited. However, dose adjustments may have important clinical and economic implications. AIMS: To study the dose adjustments of individual biologics over time in real-world practice in Sweden. METHODS: A retrospective observational study of adults with moderate to severe psoriasis was conducted based on Swedish national registry data from 2010 to 2018. Treatment episodes were identified for individual patients from the date of drug dispensation to the end of the supply of the drug. Dosing data were expressed as the proportion of treatment episodes with accumulated syringes/vials equal to, above or below the recommended guidelines. Real-world costs were calculated and compared with costs predicted from dosing guidelines. RESULTS: The mean dose was above recommended levels for all biologics investigated. Weighted mean dose adjustments for adalimumab, etanercept, secukinumab and ustekinumab were 13%, 23%, 8% and 3%, respectively, over the entire treatment period. Higher doses translate to higher costs, including notable increases over time vs. expected costs for secukinumab. CONCLUSIONS: Dose adjustments of biologics are frequent in clinical practice but differ for the various biologics. The mean observed increases in dose above guideline recommendations might indicate perceptions of suboptimal efficacy for biologics, with implications for the cost and cost-effectiveness of these treatments. Further research is warranted to understand the reasons for dose adjustments in clinical practice.

Cost-effectiveness of tildrakizumab for the treatment of moderate-to-severe psoriasis in the United States.

OBJECTIVE: To evaluate the relative cost-effectiveness of tildrakizumab and other biologic and targeted systemic treatments compared with a mix of topical therapies, phototherapies, and other conventional systemic therapies as first-line treatment for moderate-to-severe plaque psoriasis from a United States payer's perspective. METHODS: A Markov model consisting of health states based on Psoriasis Area Severity Index (PASI) response rate categories and death was developed. The probabilities of achieving PASI responses were derived from a network meta-analysis based on published efficacy data. Health care costs and effectiveness measured in quality-adjusted life-years (QALYs) were estimated. Incremental costs per QALY gained of each biologic/targeted first-line treatment versus a mix of conventional treatments were compared to provide relative cost-effectiveness among biologic and targeted first-line treatments. RESULTS: Over 10 years, the incremental cost per QALY gained compared with a mix of topical therapies, phototherapies, and other oral systemic therapies was lowest for brodalumab, infliximab, apremilast, and tildrakizumab, followed by secukinumab, ixekizumab, guselkumab, adalimumab, ustekinumab, and etanercept. The position of tildrakizumab relative to the other treatments remained the same across multiple scenarios. CONCLUSIONS: Tildrakizumab is among the most cost-effective first-line therapies for moderate-to-severe plaque psoriasis and is more cost-effective than secukinumab, ixekizumab, guselkumab, adalimumab, ustekinumab, and etanercept.

Impact of PASI response on work productivity and the effect of risankizumab on indirect costs using machine learning in patients with moderate-to-severe psoriasis.

OBJECTIVES: To compare the impact of Psoriasis Area and Severity Index (PASI) response on total work productivity impairment (TWPI) in patients with moderate-to-severe psoriasis; to compare TWPI and associated indirect costs among patients treated with risankizumab, adalimumab, ustekinumab, and placebo. METHODS: Data from REVEAL (adalimumab phase III trial) were used to assess differences in trial-observed TWPI across PASI response cohorts. A machine learning model used REVEAL data to predict TWPI for patients in the risankizumab trials. These values were used to estimate work loss hours and work impairment-related indirect costs for each treatment cohort. RESULTS: Among REVEAL patients (N = 741), TWPI in the PASI 100, 90-99, 75-89 cohorts was lower than the PASI <75 cohort (p < .05); mean TWPI was lowest with PASI 100 (1.7%) vs. 90-99 (2.5%) vs. 75-89 (4.8%) vs. <75 (14.3%). There was a significant (p < .0001) monotonic relationship between higher PASI response and lower TWPI. In the risankizumab trials (N = 2046), incremental TWPI relative to risankizumab was 3.4%/week for ustekinumab/adalimumab, and 17.1%/week for placebo; incremental indirect cost savings for risankizumab were $2179/year vs. adalimumab, $2321/year vs. ustekinumab, and $11,284/year vs. placebo. CONCLUSIONS: Higher PASI responses were associated with reduced TWPI. Risankizumab was associated with less work impairment/indirect costs vs. ustekinumab/adalimumab/placebo.

Health Economic Assessment of Optimal Biological Treatment for Moderate-to-Severe Psoriasis.

BACKGROUND: There is limited guidance on which biologic therapies should be prioritised for the treatment of moderate-to-severe psoriasis, amongst the many available options. New mode-of-action biologics, as well as recently available biosimilars for existing biologics, continue to be developed making the choice of treatment sequence increasingly complex. OBJECTIVES: The aim of this analysis was to develop a cost-effectiveness model to determine the optimal placement of biologic therapies on the treatment pathway for psoriasis in the UK. METHODS: A cohort-based Markov model was developed in Microsoft Excel, from the perspective of the National Health Service and Personal and Social Services in the UK. The model followed a hypothetical cohort of patients over a lifetime. The health states in the model were defined by Psoriasis Area and Severity Index response. In the model, patients could receive a total of four separate treatments, including three active interventions and best supportive care. RESULTS: A fully incremental analysis was undertaken on a subset of commonly used treatment sequences. The results of the list price analyses determined the most cost-effective sequence to be adalimumab biosimilar followed by ustekinumab, secukinumab, then best supportive care. This sequence is associated with total costs of £78,731 and total quality-adjusted life-years of 14.74 over a patient's lifetime. CONCLUSIONS: This research suggests that the optimal first-line treatment in the UK is adalimumab biosimilar. The optimal second-line and third-line treatments depend on the magnitude of confidential discounts applied to the biologic treatments.

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.

Ustekinumab en enfermedad de crohn / Ustekinumab in Crohn's disease

INTRODUCCIÓN: La enfermedad de Crohn (EC), al igual que la colitis ulcerosa (CU), es una enfermedad inflamatoria intestinal (EII), de curso crónico, que afecta principalmente al colon y al intestino delgado.La EC se caracteriza por episodios recurrentes y remisiones, manifestándose con diarrea, dolor abdominal, sangrado gastrointestinal y pérdida de peso, dependiendo de la gravedad y de la localización. Al exámen pueden encontrarse signos de deshidratación, desnutrición, anemia y malabsorción, como también la presencia de masas abdominales y, hasta en un tercio de los pacientes, compromiso perianal. También puede tener Manifestaciones extraintestinales como las reumatológicas, dermatológicas, oftalmológicas, colangitis esclerosante primaria, tromboembolismo venoso. Los hallazgos de laboratorio más frecuentes son la anemia, trombocitosis, ipoalbuminemia y elevación de la proteína C-reactiva. Los biomarcadores fecales como la calprotectina se correlacionan con actividad inflamatoria por neut

Cost-effectiveness of tofacitinib compared with infliximab, adalimumab, golimumab, vedolizumab and ustekinumab for the treatment of moderate to severe ulcerative colitis in Germany.

OBJECTIVES: Tofacitinib is an oral, small molecule Janus kinase (JAK) inhibitor for the treatment of ulcerative colitis (UC). This study assessed the cost-effectiveness of tofacitinib versus other available treatments for patients with moderate to severe UC following an inadequate response to conventional treatment and who are either naïve to or have failed previous biologics in Germany. METHODS: A Markov cohort model was developed to evaluate the differences in long-term costs and outcomes between tofacitinib and its comparators from the perspective of German statutory health insurance (SHI) for patients either naïve or exposed to biologics. Tofacitinib was compared to infliximab, infliximab biosimilar, adalimumab, adalimumab biosimilar, golimumab, vedolizumab, ustekinumab, and conventional therapy. Health states modeled were remission, treatment response, active UC, and post-colectomy. Patients not responding to treatment could switch to a different treatment. Treatment efficacy for induction and maintenance phases were assessed by a systematic literature review (SLR) and network meta-analysis (NMA). The model included costs associated with drug administration, adverse events, and medical resource use. Extensive deterministic and probabilistic sensitivity analyses (DSA and PSA) were conducted. RESULTS: Over a life-time horizon, patients treated with tofacitinib gained 0.035-0.083 quality-adjusted life-years (QALYs) and had direct cost savings to the SHI of €4,228-€17,184 compared to biologic treatments other than adalimumab biosimilar. When compared to adalimumab biosimilar, treatment with tofacitinib resulted in an incremental cost-effectiveness ratio (ICER) of €17,497 per QALY gained and can be considered a cost-effective alternative. Compared with conventional therapy, tofacitinib resulted in a lower ICER than all other biologics. The DSA showed that the model results were most influenced by differences in treatment efficacy. The PSA suggested confidence in the base-case results considering uncertainty around parameters. CONCLUSIONS: The results of this economic model suggest tofacitinib is a cost-effective treatment option for patients with moderate to severe UC in Germany.

Comparative cost-effectiveness of tildrakizumab and other commonly used treatments for moderate-to-severe psoriasis.

OBJECTIVES: To compare the cost-effectiveness of tildrakizumab with other commonly used biologics and apremilast as the first-line treatment for moderate-to-severe plaque psoriasis from a US health plan's perspective. METHODS: A 10-year cost-effectiveness model was developed to compare the incremental cost per extra month with a Psoriasis Area and Severity Index (PASI) 75 response. Patients were assumed to receive one of the treatments evaluated as their first-line treatment at the outset of the analysis. Nonresponders (PASI <75) discontinued their current treatment; 25% went on to receive a mix of topical therapies, phototherapies, and other systemic therapies, while 75% received a second-line therapy before receiving a mix of topical therapies, phototherapies, and other systemic therapies. Direct medical costs were calculated based on drug acquisition, administration, and monitoring costs. RESULTS: The incremental cost per extra month a patient had a PASI 75 response was lowest for brodalumab ($3,685), infliximab ($4,102), apremilast ($4,770), and tildrakizumab ($5,150), followed by risankizumab ($5,319), secukinumab ($5,675), guselkumab ($5,784), ixekizumab ($5,900), adalimumab ($5,943), ustekinumab ($6,131), etanercept ($6,618), and certolizumab pegol ($13,476). CONCLUSION: Tildrakizumab was among the most cost-effective first-line treatments for moderate-to-severe psoriasis and was more cost-effective than risankizumab, secukinumab, guselkumab, ixekizumab, adalimumab, ustekinumab, etanercept, and certolizumab pegol.

Real-world treatment patterns and healthcare costs of biologics and apremilast among patients with moderate-to-severe plaque psoriasis by metabolic condition status.

OBJECTIVES: To compare treatment patterns and costs among psoriasis patients with and without metabolic conditions newly initiating a biologic or apremilast. METHODS: Adult patients included had ≥1 prescription for secukinumab, adalimumab, ustekinumab, etanercept, or apremilast between 01/01/2015 and 08/31/2018 (date of first prescription was index date) and no index drug use in the 12-months pre-index, and continuous enrollment in the 12-month pre-index and 24-month post-index periods. Patients were divided into mutually exclusive treatment cohorts and stratified by their pre-index metabolic condition status. Treatment patterns (adherence, non-persistence, switching, discontinuation, use of combination therapy, and re-initiation) and healthcare costs were compared. RESULTS: Overall, 7773 patients were included; 47.5-56.7% had a metabolic condition. Except for the apremilast group, patients with metabolic conditions had higher discontinuation (secukinumab: 50.6% vs. 43.7%; adalimumab*: 53.9% vs. 48.7%; ustekinumab*: 41.9% vs. 35.1%; etanercept: 42.8% vs. 41.2%; apremilast: 43.1% vs. 46.1%) and switching (secukinumab: 48.1% vs. 41.2%; adalimumab*: 47.8% vs. 41.9%; ustekinumab*: 34.5% vs. 25.3%; etanercept*: 53.6% vs. 51.5%; apremilast: 45.8% vs. 44.6%) than patients without (*p < .05). Patients with metabolic conditions incurred significantly higher costs. CONCLUSION: Many psoriasis patients initiating biologics or apremilast had metabolic conditions. These patients had higher discontinuation and switching, and significantly higher healthcare costs.