In-Depth Assessment of Endoscopic Remission in Inflammatory Bowel Disease Treated by Anti-TNF or Vedolizumab.

BACKGROUND AND AIMS: Confocal endomicroscopy is a technique allowing the in vivo assessment of the superficial layers of the mucosa. Preliminary studies have already suggested its added value in the assessment of endoscopic remission in inflammatory bowel disease. However, most of these studies were performed on patients still having incomplete mucosal healing. Our aim was to disclose persisting endomicroscopic anomalies in patients with full endoscopic remission and to compare them between vedolizumab- and anti-tumor necrosis factor-treated patients. METHODS: We screened patients with Crohn's disease (CD) or ulcerative colitis (UC) treated for more than 6 months with biologic therapy, and being in steroid-free clinical and biological remission. White light endoscopy and probe-based confocal laser endomicroscopy (pCLE) analysis were performed in the ileum, right colon, transverse colon, left colon, and rectum. Full endoscopic remission was defined by a Mayo endoscopic score of 0 in UC and no remaining ulcer or erosion in CD. Patients were prospectively followed up and clinical relapses were recorded. RESULTS: Seventy-two CD and UC patients treated by biologic therapy and in clinical and biological remission were screened. A total of 37 were also in full endoscopic remission and were included in our study; 183 intestinal segments were analyzed. We found residual pCLE anomalies in most of the patients. These anomalies were not significantly associated with any demographic or clinical characteristic including the treatment received, nor were they associated with histological parameters, levels of C-reactive protein or fecal calprotectin. Among the 37 patients, 7 (18.9%) relapsed over a median follow-up of 33.7 months. The risk of relapse was not associated with any clinical, biological, histologic, or pCLE feature at baseline. CONCLUSION: Despite endoscopic, biological, and even histological remission, we found a high prevalence of endomicroscopic abnormalities, which were not different between anti-tumor necrosis factor- and vedolizumab-treated patients. The clinical significance of these anomalies remains to be clarified.

We studied the abnormalities found by confocal endomicroscopy in patients with chronic inflammatory disease in deep endoscopic remission under immunosuppressive treatment. Relapse was not associated with the abnormalities found, which, although numerous, remain of unknown significance.

Cost-effectiveness of tumor necrosis factor-alpha inhibitors: a systematic review and meta-analysis of cost-utility studies.

OBJECTIVE: To systematically review the cost-utility evidence of TNF-a-i treatment for rheumatoid arthritis (RA) and to estimate the pooled incremental net benefit (INBp). METHODS: We selected economic evaluation studies reporting the cost-utility of TNF-a-i compared to other disease-modifying anti-rheumatic drugs (DMARDs) after a systematic search in PubMed, Embase, Scopus, and Tufts Medical Centers' cost-effective analysis registry. The results were reported as pooled INB in purchasing power parity-adjusted US dollars, along with 95% confidence intervals. We used GRADE quality assessment to present summaries of evidence and random-effects meta-analysis to synthesize cost-utility of TNF-a-i. RESULTS: We included 86 studies for systematic review, of which 27 for meta-analysis. TNF-a-i is not cost-effective [$ -4,129(-6,789 to -1,469)] compared to other DMARDs but with high heterogeneity. There was no evidence of publication bias (p = 0.447). On separate analysis, TNF-a-i is not cost-effective [$ -4,805(-7,882 to -1,728)] compared to conventional synthetic DMARDs for RA treatment. GRADE assessment indicated very low confidence in pooled cost-utility results and likely presence of risk of bias on the overall ECOBIAS checklist in studies. CONCLUSION: Based on the available evidence during the study period, TNF-a-i is not a cost-effective option for treating RA compared to other DMARDs. However, high heterogeneity and low confidence in GRADE quality assessment preclude the results from being generalizable.

Risk of cancer, cardiovascular disease, thromboembolism, and mortality in patients with rheumatoid arthritis receiving Janus kinase inhibitors: a real-world retrospective observational study using Korean health insurance data.

OBJECTIVES: This study investigated whether Janus kinase inhibitors (JAKis) raise the risk of cardiovascular disease (CVD), venous thromboembolism (VTE), and cancer in patients with rheumatoid arthritis (RA). METHODS: We conducted a real-world retrospective observational study using data obtained from the Korean National Health Insurance Service database. Two data sets were analyzed: tumor necrosis factor inhibitor (TNFi)/JAKi-naive RA patients (set 1) and all RA patients who used TNFis or JAKis (set 2). The incidence rate ratios (IRRs) and hazard ratios (HRs) for acute myocardial infarction (AMI), stroke, cardiovascular (CV)-related mortality, major adverse cardiovascular events (MACE), VTE, arterial thromboembolism (ATE), cancer, and all-cause mortality were compared between the JAKi and TNFi groups. RESULTS: Set 1 included 1,596 RA patients (JAKi group: 645; TNFi group: 951), and set 2 included 11,765 RA patients (JAKi group: 2,498; TNFi group: 9,267). No adverse events (AEs) showed significantly higher IRRs in the JAKi groups than in the TNFi groups of sets 1 and 2. The HRs for MACE in the JAKi groups of sets 1 and 2 were 0.59 (95% confidence [CI], 0.35 to 0.99) and 0.80 (95% CI, 0.67 to 0.97), respectively. The JAKi group of set 2 showed a significantly higher risk of all-cause mortality (HR, 1.71; 95% CI, 1.32 to 2.20), but the other AEs did not demonstrate increased risks in the JAKi groups. CONCLUSIONS: In this study, JAKis did not increase the risk of AMI, stroke, CV-related mortality, MACE, VTE, ATE, or cancer in Korean RA patients relative to TNFis.

Assessment of clinical, biochemical, and radiological outcomes following intra-articular injection of Wharton jelly-derived mesenchymal stromal cells in patients with knee osteoarthritis: A prospective clinical study.

The aim of the present study was to perform clinical, biochemical, and radiological evaluation of the efficacy of mesenchymal stem cells derived from Wharton jelly (WJ) present within the human umbilical cord in the treatment of knee osteoarthritis. Between 2018 and 2019, 10 patients with knee osteoarthritis for whom the conservative treatment was not beneficial were included in the study. Patients were clinically, radiologically, and biochemically evaluated before treatment initiation. Thereafter, the patients were intra-articularly injected using a solution containing 1 × 108 WJ-derived MSCs. Evaluations were performed on day 21 (V1) and 42 (V2) and month 3 (V3), 6 (V4), and 12 (V5) after the procedure. At 1-year post-injection, visual analogue scale, Western Ontario and McMaster Universities Osteoarthritis Index, and Lequesne scores of patients were lower than those observed during the initial evaluation, whereas the mean 36-Item Short Form Health Survey score was higher. Cartilage thicknesses were found to be increased in all regions except in the medial femur, medial posterior femur, lateral posterior femur, and lateral posterior tibia regions in magnetic resonance imaging. A significant increase was observed in tumor necrosis factor-alpha, interleukin-1ß, adiponectin, resistin, and interleukin-6 levels compared with pre-injection values. The leptin levels at 6-month and 1-year controls were lower than the pre-injection levels, and the decrease observed at 6 months was significant. In patients with knee osteoarthritis, intra-articular WJ-derived MSC injection causes significant pain reduction, satisfactory functional improvement, and increased patient satisfaction following a 1-year follow-up. These clinical improvements were supported by magnetic resonance images, along with changes in adiponectin and leptin levels in synovial fluid. Level of evidence: IV.

The economic burden of biologic disease-modifying antirheumatic drugs in rheumatoid arthritis patients in the United States.

BACKGROUND: Previous U.S. economic burden estimates for rheumatoid arthritis (RA) varied from $85.6 to $148.1 billion annually. However, these estimates do not reflect comparative amounts spent on RA treatment options in addition to other medical expenditures. Therefore, this study's goal was to comparatively analyze the overall economic burden of U.S. patients treated for RA using conventional disease-modifying antirheumatic drugs (DMARDs) versus TNF alpha biologic DMARDs. RESEARCH DESIGN AND METHODS: This retrospective observational study analyzed Medical Expenditure Panel Survey Household Component data from 2016 to 2018. Healthcare utilization, total medical expenditures, and out-of-pocket expenditures were compared between RA medication groups. RESULTS: Three hundred twenty-five adult RA patients experiencing 603 RA-related events, including at least one medical visit, were identified. Rheumatic arthritis-attributable medical expenditures among patients prescribed DMARDs were $11.4 billion. Average total medical expenditures were significantly higher for the TNF alpha biologic group $26,216.67 (95% CI: $19,502.84-$32,930.5) versus $5,388.52 (95% CI: $2,768.25-$8,008.79) for the conventional DMARD group (p < 0.001). CONCLUSIONS: RA patients receiving TNF alpha biologics experienced significantly higher total medical and out-of-pocket expenditures; however, they experienced fewer or no occurrences of high-cost drivers of healthcare utilization compared to patients receiving conventional DMARDs.

This study shows that rheumatoid arthritis (RA) patients with biologic-containing disease-modifying antirheumatic drugs (DMARDs) encountered significantly higher total medical expenditures as well as out-of-pocket (OOP) expenditures versus those with conventional DMARDs. The average total medical expenditures were $26,216.67 in the tumor necrosis factor (TNF) alpha biologic group and $5,388.52 in the conventional DMARD group. However, even with higher total medical expenditures, data suggests the TNF alpha biologic group experienced fewer emergency room visits, less home health services, and no hospitalizations compared to the conventional DMARD group.

Vedolizumab Is Associated With a Lower Risk of Serious Infections Than Anti-Tumor Necrosis Factor Agents in Older Adults.

BACKGROUND & AIMS: Despite the increased numbers of older adults with inflammatory bowel diseases (IBDs), there are few studies regarding the safety and effectiveness of IBD treatments in older adults. The aim of this study was to compare the safety and effectiveness of anti-tumor necrosis factor (TNF)-α agents and vedolizumab in older adults with IBD. METHODS: We conducted a retrospective cohort study using an active comparator, new-user design for adults age 65 years and older with IBD initiating anti-TNF-α agents and vedolizumab in the Medicare claims database from 2014 to 2017. The primary safety outcome was infection-related hospitalization (excluding intra-abdominal and perianal abscesses). Co-primary outcomes to estimate effectiveness were IBD-related hospitalization, IBD-related surgery, and new corticosteroid use 60 days or more after biologic initiation. We performed propensity score weighting to control for confounding and estimated adjusted hazard ratios and 95% confidence intervals using standardized morbidity ratio-weighted variables. RESULTS: We identified 1152 anti-TNF-α new users and 480 vedolizumab new users. The median age was 71 years in both cohorts and 11% were age 80 years or older. Crohn's disease patients comprised 54% of the anti-TNF-α cohort and 57% of the vedolizumab cohort. There was no significant difference in demographics, health care utilization, or frailty in both cohorts. More than half of both cohorts had a Charlson comorbidity index of 2 or higher. Vedolizumab users had a decreased risk of infection-related hospitalization (adjusted hazard ratio, 0.47; 95% confidence interval, 0.25-0.86). There was no significant difference in the outcomes approximating effectiveness. CONCLUSIONS: Older IBD patients treated with vedolizumab had a lower risk of infection-related hospitalization compared with those initiating anti-TNFs. We observed no difference in effectiveness defined by hospitalizations, surgery, or new corticosteroid use.

Risk and cost of infection-related hospitalizations in medicare beneficiaries with comorbid rheumatoid arthritis treated with abatacept versus other targeted disease-modifying anti-rheumatic drugs.

OBJECTIVE: This study evaluated infection-related hospitalization risk and cost in tumor necrosis factor inhibitor (TNFi)-experienced and targeted DMARD (tDMARD) naïve rheumatoid arthritis (RA) patients that were treated with abatacept, TNFi, or other non-TNFi. METHODS: This retrospective study used 100% Medicare Fee-for-Service claims to identify patients ≥65 age, diagnosed with RA, and were either 1) TNFi-experienced, who switched from a TNFi to another tDMARD (subsequent tDMARD claim served as index), or 2) tDMARD naïve (first therapy claim served as index), who initiated either abatacept, TNFi, or non-TNFi as their first tDMARD, between 2010 and 2017. Follow-up ended at the date of disenrollment, death, end of study period, or end of index treatment, whichever occurred first. Infection-related hospitalizations included pneumonia, bacterial respiratory, sepsis, skin and soft tissue, joint or genitourinary infections. A Cox proportional hazard model and two part generalized linear model were developed to estimate adjusted infection-related hospitalization risk and costs. Costs were normalized to per-patient-per-month (PPPM) and inflated to 2019 US$. RESULTS: The infection-related hospitalizations rate was lower during follow-up than during baseline periods for abatacept users, but was reversed for both TNFi and other non-TNFi users in both TNFi-experience and tDMARD naïve (p value < .001 based on Breslow-Day test for homogeneity of odds ratios). Infection-related hospitalization PPPM cost was significantly lower in abatacept treated patients compared to TNFi (TNFi-experienced: by $74; tDMARD naïve: $42) and other non-TNFi (TNFi-experienced: by $68; tDMARD naïve: $60). The adjusted infection-related hospitalization risk was significantly higher for RA patients treated with TNFi (TNFi-experienced HR: 1.48; 95% CI: 1.26-1.75, p < .0001; tDMARD naïve HR:1.59; 95% CI: 1.43-1.77, p < .0001) and other non-TNFi (TNFi-experienced HR:1.46; CI:1.28-1.66; tDMARD naïve HR:1.63; 95% CI: 1.44-1.83) than with abatacept. CONCLUSION: RA Medicare Fee-For-Service beneficiaries who either switched or initiated abatacept have a lower infection-related hospitalization risk and cost compared to patients who switched to or initiated other tDMARDs.

Reduced risk of mortality associated with systemic psoriasis treatment in the Psoriasis Longitudinal Assessment and Registry (PSOLAR): A nested case-control analysis.

BACKGROUND: The effects of systemic therapy on mortality risk among patients with psoriasis are not fully understood. OBJECTIVE: To evaluate the impact of systemic treatment on mortality risk in patients enrolled in the Psoriasis Longitudinal Assessment and Registry. METHODS: Nested case-control analyses were performed to estimate mortality risk. Cases were defined as patients who died while participating in the Psoriasis Longitudinal Assessment and Registry. Cases were matched (1:4) with controls by age, race, sex, and geographic region. Evaluated treatments included methotrexate, ustekinumab, and tumor necrosis factor α inhibitors. Exposure was defined as at least 1 dose of treatment within 3 months before death and was stratified by duration of therapy. RESULTS: Among 12,090 patients, 341 deaths occurred, matched to 1364 controls. Biologic treatment within the preceding 3 months was protective against mortality versus no exposure: odds ratio (OR) for exposure of less than 1 year, 0.08 (95% confidence interval [CI], 0.03-0.23); OR for exposure of 1 year or longer, 0.09 (95% CI, 0.06-0.13). Methotrexate was protective against mortality only with exposure for 1 year or longer (OR, 0.08; 95% CI, 0.02-0.28). LIMITATIONS: Observational studies are subject to unmeasured confounding. CONCLUSIONS: Biologic therapy was associated with reduced mortality risk in patients with moderate to severe psoriasis, regardless of treatment duration; methotrexate reduced risk only with exposure for 1 year or longer.

Healthcare use, work loss and total costs in incident and prevalent Crohn's disease and ulcerative colitis: results from a nationwide study in Sweden.

BACKGROUND: There are limited data on population-wide assessment of cost in Crohn's disease (CD) and ulcerative colitis (UC). AIM: To estimate the societal cost of actively treated CD and UC in Sweden. METHODS: We identified 10 117 prevalent CD and 19 762 prevalent UC patients, aged ≥18 years on 1 January 2014 and 4028 adult incident CD cases and 8659 adult incident UC cases (2010-2013) from Swedish Patient Register. Each case was matched to five population comparators. Healthcare costs were calculated from medications, outpatient visits, hospitalisations and surgery. Cost of productivity losses was derived from disability pension and sick leave. RESULTS: The mean annual societal costs per working-age patient (18-64 years) with CD and UC were $22 813 (vs $7533 per comparator) and $14 136 (vs $7351 per comparator), respectively. In patients aged ≥65 years, the mean annual costs of CD and UC were $9726 and $8072 vs $3875 and $4016 per comparator, respectively. The majority of cost for both CD (56%) and UC (59%) patients originated from productivity losses. Higher societal cost of working-age CD patients as compared to UC patients was related to greater utilisation of anti-TNF (22.2% vs 7.4%) and increased annual disability pension (44 days vs 25 days). Among incident CD and UC patients, the mean total cost over the first year per patient was over three times higher than comparators. CONCLUSION: In Sweden, the societal cost of incident and prevalent CD and UC patients was consistently two to three times higher than the general population.

Healthcare-Related Costs Associated with Switching Subcutaneous Tumor Necrosis Factor-α Inhibitor in the Treatment of Inflammatory Arthritis: a Retrospective Study.

INTRODUCTION: Subsequent lines of subcutaneous tumor necrosis factor alpha inhibitor (SC-TNFi) treatment may be well motivated in the management of rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA)-collectively named inflammatory arthritis (IA). However, the costs associated with switching SC-TNFis are largely unknown. The objective of this retrospective observational study was to explore costs of healthcare resource utilization (HCRU) associated with switching SC-TNFi treatment among biologic-naïve Swedish patients with IA. METHODS: Using population-based register data, adult patients filling prescriptions between May 6, 2010 and December 31, 2014 for an SC-TNFi (adalimumab, etanercept, certolizumab, and golimumab) were included. Patients switching treatment (cyclers) were matched to treatment persistent patients on the basis of propensity score and follow-up time. HCRU-associated costs were captured and compared 12 months before and 12 months after the index date (defined as the date of the switch). RESULTS: A balanced cohort of 594 matched pairs was derived. Prior to the index date, cyclers had significantly higher non-treatment HCRU costs compared to persistent patients ($3815 [3498-4147] vs. $2900; 95%CI [2565-3256]). However, 12 months after the index date, cyclers had significantly increased their non-treatment HCRU costs while persistent patients lowered theirs ($822 [232-1490] vs. $- 313 [- 664-36]). This resulted in a statistically significant difference in difference of $1135 between the groups. CONCLUSIONS: In biologic-naïve patients treated with SC-TNFi for IA, cyclers significantly increased their non-treatment HCRU costs 12 months after switching treatment while persistent patients lowered their costs during the same time period. As these findings indicate that differences in treatment persistence may have an impact on costs, further research utilizing more comprehensive data sources in alternate settings is warranted.

Stories of Patient Involvement Impact in Health Technology Assessments: A Discussion Paper.

OBJECTIVES: As more health technology assessment (HTA) bodies seek to implement patient involvement, there is a desire to learn from other HTA bodies about their experiences and understand what approaches can be used and which ones make a real difference to HTA. This is difficult, as the impact of patient involvement in HTA is not well documented. This study aims to promote further discussion about the ways in which patient involvement can impact HTAs by studying stories of impact. METHODS: In a multi-stakeholder workshop, experts leading patient involvement in four HTA bodies shared examples of HTAs where they believed patient involvement made a difference, then they reflected on these impact stories within the wider context of impact evaluation. RESULTS: The HTA bodies drew on patient input and patient-based evidence to inform their HTAs. The patient involvement was observed to elucidate patients' experiences, needs and preferences which, in turn, was observed to influence the HTA recommendations about optimal use of technologies, including taking account of issues for sub-groups, outcomes that matter to patients and educational needs. CONCLUSIONS: Personal stories of patient involvement may enable a wider understanding of different approaches to and impact of patient involvement. The examples relate to both patient input and patient-based evidence and highlight the role that patient involvement can play in reducing uncertainties and complementing the clinical and economic evidence in HTA. They suggest that impact can be seen in recommendations about how and when a technology is used.

The economic burden of switching targeted disease-modifying anti-rheumatic drugs among rheumatoid arthritis patients.

AIMS: To estimate real world healthcare costs and resource utilization of rheumatoid arthritis (RA) patients associated with targeted disease modifying anti-rheumatic drugs (tDMARD) switching in general and switching to abatacept specifically. MATERIALS AND METHODS: RA patients initiating a tDMARD were identified in IMS PharMetrics Plus health insurance claims data (2010-2016), and outcomes measured included monthly healthcare costs per patient (all-cause, RA-related) and resource utilization (inpatient stays, outpatient visits, emergency department [ED] visits). Generalized linear models were used to assess (i) average monthly costs per patient associated with tDMARD switching, and (ii) among switchers only, costs of switching to abatacept vs tumor necrosis factor inhibitors (TNFi) or other non-TNFi. Negative binomial regressions were used to determine incident rate ratios of resource utilization associated with switching to abatacept. RESULTS: Among 11,856 RA patients who initiated a tDMARD, 2,708 switched tDMARDs once and 814 switched twice (to a third tDMARD). Adjusted average monthly costs were higher among patients who switched to a second tDMARD vs non-switchers (all-cause: $4,785 vs $3,491, p < .001; RA-related: $3,364 vs $2,297, p < .001). Monthly RA-related costs were higher for patients switching to a third tDMARD compared to non-switchers remaining on their second tDMARD ($3,835 vs $3,383, p < .001). Switchers to abatacept had significantly lower RA-related monthly costs vs switchers to TNFi ($3,129 vs $3,436, p = .021), and numerically lower all-cause costs ($4,444 vs $4,741, p = 0.188). Switchers to TNFi relative to abatacept had more frequent inpatient stays after switch (incidence rate ratio (IRR) = 1.85, p = .031), and numerically higher ED visits (IRR = 1.32, p = .093). Outpatient visits were less frequent for TNFi switchers (IRR = 0.83, p < .001) compared to switchers to abatacept. LIMITATIONS AND CONCLUSIONS: Switching to another tDMARD was associated with higher healthcare costs. Switching to abatacept, however, was associated with lower RA-related costs, fewer inpatient stays, but more frequent outpatient visits compared to switching to a TNFi.

Ustekinumab in psoriatic arthritis: need for studies from real-world evidence.

Ustekinumab (UST) is a recently approved drug for the treatment of psoriatic arthritis (PsA). The ACR response rates in randomized clinical trials (RCTs) with this drug have been slightly lower than that reported in RCTs of anti-TNF and anti-IL17 therapies. Therefore, the position that this drug may occupy in the treatment algorithms of PsA is not clear. More information is needed on the true efficacy of this agent under real clinical practice conditions. In this review of real-world evidence studies, it is shown that UST is effective and safe to treat PsA; nevertheless, it is necessary to homogenize the way in which the main outcomes and treatment objectives of these studies are presented.

Secuquinumabe para o tratamento de artrite psoriásica em pacientes adultos com resposta inadequada a medicamentos modificadores do curso da doença sintéticos ou biológicos da classe anti-TNF / Secuquinumabe for or treatment of psoriatic arthritis in adult patients with inadequate response to drugs modifying the synthetic or biological course of anti-TNF drugs

CONTEXTO: A artrite psoriásica (AP) é uma artrite inflamatória crônica, autoimune, que acomete entre 0,06 e 0,25% da população. O tratamento envolve medidas não farmacológicas e o uso de anti-inflamatórios não esteroidais (AINEs), glicocorticoides e medicamentos modificadores do curso da doenças (MMCD) sintéticos e biológicos, segundo o tipo de acometimento predominate (AP periférica ou axial). Os medicamentos biológicos são indicados em caso de falha ao tratamento prévio com os AINES e MMCD sintéticos (AP periférica) ou AINES (AP axial), constituindo a última linha de tratamento da doença. TECNOLOGIA: SECUQUINUMABE (COSENTYX®). INDICAÇÃO: ARTRITE PSORIÁSICA. PERGUNTA: Secuquinumabe é eficaz e seguro para o tratamento da artrite psoriásica ativa, quando a resposta à terapia prévia com medicamentos modificadores do curso da doença (MMCD), sintéticos ou biológicos, for inadequada? EVIDÊNCIAS CIENTÍFICAS: Foram incluídos três ensaios clínicos e quatro revisões sistemáticas de comparação direta de secuquinumabe contra placebo e indireta com relação aos demais biológicos disponíveis no SUS. Comparações indiretas demonstraram eficácia equivalente entre secuquinumabe e os medicamentos anti-TNF disponíveis no SUS, porém estes estudos apresentaram baixa qualidade metodológica. Dados dos ensaios clínicos randomizados FUTURE 1 e FUTURE 2 demonstraram que secuquinumabe 150 mg é eficaz em 24 semanas, comparado a placebo, para os desfechos de AP periféricos (ACR20, ACR50, ACR 70, DAS28 e entesite), de pele (PASI75, PASI 90), e para redução da progressão radiográfica. Para pacientes com falha ao anti-TNF, apenas sequinumabe 300 mg foi mais eficaz que placebo (FUTURE II). Para pacientes com psoríase e artrite psoriásica concomitante, sequinumabe 300 mg foi mais eficaz que placebo e que etanercepte (ERASURE e FIXTURE). Com relação aos resultados de segurança, as taxas de eventos adversos, eventos adversos sérios e descontinuação por eventos adversos foram semelhantes entre os grupos secuquinumabe e placebo até 16 semanas de acompanhamento, porém a ocorrência de infecções ou infestações foi maior entre pacientes que receberam secuquinumabe. Ao final de 104 semanas, 84,5% dos pacientes que utilizaram secuquinumabe relataram pelo menos um evento adverso, sendo a ocorrência de infecções ou infestações os mais comuns. AVALIAÇÃO ECONÔMICA: A análise de custo minização sugere que secuquinumabe na dose de 150 mg é mais barato em comparação com os medicamentos anti-TNF disponíveis no SUS em todos os cenários propostos. Secuquinumabe 300 mg é mais caro que adalimumabe, etanercepte e golimumabe no primeiro ano de uso e mais caro que golimumabe a partir do segundo ano. Esta análise foi sensível à redução de 10% no preço de aquisição dos medicamentos disponíveis no SUS, favorecendo os medicamentos já incorporados. AVALIAÇÃO DE IMPACTO ORÇAMENTÁRIO: A análise de impacto orçamentário apresentada sugere economia de até R$ 60 milhões de reais com a incorporação de secuquinumabe em cinco anos, o que representa 4% do total gasto com AP. Entretanto, parâmetros estimados no modelo estão inadequados e podem influenciar o resultado final, tais como: baixo índice de troca entre os medicamentos biológicos; constante e elevado market share para o secuquinumabe; taxa de descontinuação sem troca de 0%. Decisão: Incorporar incorporar o secuquinumabe para o tratamento de artrite psoriásica em pacientes adultos com resposta inadequada a medicamentos modificadores do curso da doença sintéticos ou biológicos da classe anti-TNF no âmbito do Sistema Único de Saúde ­ SUS, dada pela Portaria nº 3, publicada no DOU nº 18, do dia 25 de janeiro de 2018, seção 1, pág. 123.(AU)

[OPTIMIZATION OF TREATMENT BY ANTIBODIES AGAINST TNF-α IN INFLAMMATORY BOWEL DISEASE].

INTRODUCTION: Treatment selection for inflammatory bowel disease involves many considerations. Anti-TNF - α agents are one of the major available therapeutic tools for these diseases. Loss of response to anti- TNF - α agents is relatively common and results mostly, but not exclusively, from the development of immunogenicity against the drug. Assessment of disease activity in parallel to measurement of drug levels and anti-drug antibodies allows for treatment optimization in patients who develop clinical loss of response. For patients in remission, treatment optimization can be performed by the evaluation of risk factors for disease flare assisted by assessment of drug levels and the presence of antibodies. Various algorithms can be used to make a decision that will lead to better clinical outcomes and a better cost-effectiveness ratio. Professor Yehuda Chowers has received consultancy fees from Abbot and Schering-Plough.

Second-line treatment persistence and costs among patients with immune-mediated rheumatic diseases treated with subcutaneous TNF-alpha inhibitors.

The objective of this study was to describe treatment persistence with second-line subcutaneous tumor necrosis factor-alpha inhibitors (SC-TNFis) in patients with immune-mediated rheumatic diseases (IMRDs) in Sweden, and the impact of non-persistence on healthcare costs. This retrospective observational study was based on Swedish national health register data. Adults were identified through filled prescriptions for adalimumab (ADA), etanercept (ETA), certolizumab pegol (CZP) and golimumab (GLM). Persistence was estimated over 3 years for propensity score-matched (PSM) cohorts using non-parametric survival analysis. Unadjusted comparisons of costs comprised specialized outpatient care, inpatient care, and medication. In total, N = 845 patients were identified and three PSM cohorts were generated (GLM vs. ADA, ETA, and CZP, respectively). GLM exhibited higher persistence than ADA over the study period (p = 0.040), and numerically higher persistence than ETA and CZP for 36 and 30 months, respectively. Persistent and non-persistent patients had similar mean total cost at 12 month pre-treatment ($5185 vs. $5064, p = 0.750). During the 12 month post-treatment initiation, persistent patients had lower mean total costs ($4377 vs. $6605), corresponding to a cost difference of $2228 (p < 0.001). In second-line treatment with SC-TNFis for IMRDs in Sweden, GLM exhibited significantly higher persistence than ADA over the course of the study. Similarly, GLM showed numerically higher persistence than ETA and CZP, which is concurrent with results observed in first-line SC-TNFi treatment. Considering the lower healthcare costs for persistent patients, the choice of second-line SC-TNFi among eligible patients may merit careful consideration given its impact on patients and payers.

Risk of malignancy with systemic psoriasis treatment in the Psoriasis Longitudinal Assessment Registry.

BACKGROUND: The effect of systemic therapy on malignancy risk among patients with psoriasis is not fully understood. OBJECTIVE: Evaluate the impact of systemic treatment on malignancy risk among patients with psoriasis in the Psoriasis Longitudinal Assessment and Registry (PSOLAR). METHODS: Nested case-control analyses were performed among patients with no history of malignancy. Cases were defined as first malignancy (other than nonmelanoma skin cancer) in the Psoriasis Longitudinal Assessment and Registry, and controls were matched by age, sex, geographic region, and time on registry. Study therapies included methotrexate, ustekinumab, and tumor necrosis factor-α (TNF-α) inhibitors. Exposure was defined as 1 or more doses of study therapy within 12 months of malignancy onset and further stratified by duration of therapy. Multivariate conditional logistic regression, adjusted for potential confounders, was used to estimate odds ratios of malignancies associated with therapy. RESULTS: Among 12,090 patients, 252 malignancy cases were identified and 1008 controls were matched. Treatment with methotrexate or ustekinumab for more than 0 months to less than 3 months, 3 months to less than 12 months, or 12 months or longer was not associated with increased malignancy risk versus no exposure. Longer-term (≥12 months) (odds ratio, 1.54; 95% confidence interval, 1.10-2.15; P = .01), but not shorter-term treatment, with a TNF-α inhibitor was associated with increased malignancy risk. LIMITATIONS: Cases and controls could belong to 1 or more therapy categories. CONCLUSIONS: Long-term (≥12 months) treatment with a TNF-α inhibitor, but not methotrexate and ustekinumab, may increase risk for malignancy in patients with psoriasis.

Histological response assessment following neoadjuvant isolated limb perfusion in patients with primary, localised, high-grade soft tissue sarcoma.

PURPOSE: Histological response assessment following neoadjuvant treatment can help identify patients at a higher risk for systemic disease progression. Our goal was to evaluate whether mitotic count and the amount of viable tumour following neoadjuvant isolated limb perfusion (ILP) for primary, locally advanced, non-metastatic, high-grade extremity soft tissue sarcoma correlate with prognosis. PATIENTS AND METHODS: This study is a retrospective analysis of 61 patients who underwent neoadjuvant ILP followed by surgical resection with curative intent between 2001 and 2011. Non-parametric analyses were carried out with the Mann-Whitney U and the Wilcoxon signed-rank test. Survival curves were calculated with the Kaplan-Meier method and compared with the log-rank test. RESULTS: The median follow-up was 44 months for all patients and 55 months for survivors. The amount of viable tumour after ILP had no correlation with overall (OS) (P = 0.227) or event-free (EFS) (P = 0.238) survival probability. Patients with a low mitotic count after ILP had a significantly higher OS (P < 0.001), EFS (P = 0.002) and post-relapse survival probability (P = 0.030) compared to patients with an intermediate or high mitotic count. CONCLUSIONS: The mitotic count following ILP for primary, high-grade, locally advanced, non-metastatic soft tissue sarcoma appears to significantly correlate with prognosis. If these results are validated in a prospective setting, they could provide a rationale for the design of adjuvant systemic chemotherapy trials with the goal of improving the prognosis of patients with an intermediate or high mitotic count after ILP.

Ulcerative colitis: epidemiology, diagnosis, and management.

Ulcerative colitis is a chronic idiopathic inflammatory bowel disease characterized by continuous mucosal inflammation that starts in the rectum and extends proximally. Typical presenting symptoms include bloody diarrhea, abdominal pain, urgency, and tenesmus. In some cases, extraintestinal manifestations may be present as well. In the right clinical setting, the diagnosis of ulcerative colitis is based primarily on endoscopy, which typically reveals evidence of continuous colonic inflammation, with confirmatory biopsy specimens having signs of chronic colitis. The goals of therapy are to induce and maintain remission, decrease the risk of complications, and improve quality of life. Treatment is determined on the basis of the severity of symptoms and is classically a step-up approach. 5-Aminosalycilates are the mainstay of treatment for mild to moderate disease. Patients with failed 5-aminosalycilate therapy or who present with more moderate to severe disease are typically treated with corticosteroids followed by transition to a steroid-sparing agent with a thiopurine, anti-tumor necrosis factor agent, or adhesion molecule inhibitor. Despite medical therapies, approximately 15% of patients still require proctocolectomy. In addition, given the potential risks of complications from the disease itself and the medications used to treat the disease, primary care physicians play a key role in optimizing the preventive care to reduce the risk of complications.

Review article: a clinician's guide for therapeutic drug monitoring of infliximab in inflammatory bowel disease.

BACKGROUND: Tumour necrosis factor (TNF)-antagonists have an established role in the treatment of inflammatory bowel diseases (IBDs), however, subtherapeutic drug levels and the formation of anti-drug antibodies (ADAs) may decrease their efficacy. AIM: The evidence supporting the use of therapeutic drug monitoring (TDM) based clinical algorithms for infliximab (IFX) and their role in clinical practice will be discussed. METHODS: The literature was reviewed to identify relevant articles on the measurement of IFX levels and antibodies-to-infliximab. RESULTS: Treatment algorithms for IBD have evolved from episodic monotherapy used in patients refractory to all other treatments, to long-term combination therapy initiated early in the disease course. Improved remission rates have been observed with this paradigm shift, nevertheless many patients ultimately lose response to therapy. Although empiric dose optimization or switching agents constitute the current standard of care for secondary failure, these interventions have not been applied in an evidence-based manner and are probably not cost-effective. Multiple TDM-based algorithms have been developed to identify patients that may benefit from measurement of IFX and ADA levels to guide adjustments to therapy. CONCLUSIONS: Therapeutic drug monitoring offers a rational approach to the management of secondary failure to IFX. This concept has gained momentum based on evidence from case series, cohort studies and post-hoc analyses of randomised controlled trials.