Sustaining competition for biosimilars on the pharmacy benefit: Use it or lose it.

Congress passed the Biologic Price Competition and Innovation Act of 2009, specifically to offer market competition as a counterweight to the rising costs of biologic medicines. As of April 15, 2024, 49 biosimilars have been approved by the US Food and Drug Administration in 15 biologic categories. Biosimilar competition has been undeniably successful: Through 2022, biosimilars have saved the US health system $23.6 billion, without significant care disruption or reduced quality. Through 2023, adalimumab biosimilar competition has added an additional $6.5 billion to this total, primarily through greater rebates from the reference manufacturer. Despite launching at discounts as great as 85%, adalimumab biosimilars have not been given preferred formulary positioning in the vast majority of cases and have thus gained only 3% of market share through 2023, largely because of payers' and pharmacy benefit managers' preference for rebates over discounts. This situation may negatively influence future biosimilar development, posing a threat to a biosimilar pipeline that represents hundreds of billions in savings over the next 10 years.

Effectiveness and safety of biological and target synthetic drugs treatment for psoriatic arthritis: a systematic review with network meta-analysis.

BACKGROUND: Psoriatic arthritis (PA) is a chronic inflammatory systemic arthritis that can result in loss of functional capacity and joint deformation. This systematic review assessed the effectiveness and safety of biological and target synthetic drugs for treating PA. METHODS: We searched for randomized clinical trials (RCTs) that evaluated the use of Adalimumab, Etanercept, Infliximab, Golimumab, Secukinumab, Certolizumab Pegol and Tofacitinib in the main general databases and clinical trial registers databases. The primary outcomes were ACR 50, PsARC, and serious adverse events. Two independent reviewers performed study selection and data extraction. Network meta-analyses were conducted using a random effects model and frequentist approach. The CINeMA software was used to assess the certainty of evidence. RESULTS: We included 33 RCTs (n = 11,034). The results from the network meta-analysis for the ACR 50 at 6-months follow-up showed that all drugs were superior to placebo, with Secukinumab (high certainty of evidence), Infliximab (very low certainty of evidence) and Adalimumab (high certainty of evidence) ranking the highest. Regarding the PsARC (at 6-months follow-up), all drugs, except for Golimumab (very low certainty of evidence), were superior to placebo, with Etanercept (low certainty of evidence), Infliximab (low certainty of evidence) and Certolizumab Pegol (low certainty of evidence) being the most effective drugs. There were no significant differences in the risk of serious adverse events between the drugs and placebo. Golimumab (very low certainty of evidence), Secukinumab (low certainty of evidence), and Adalimumab (very low certainty of evidence) ranked the highest for safety. CONCLUSIONS: In conclusion, based on the balance between efficacy and safety, Secukinumab and Adalimumab may be the preferred options among the evaluated drugs for treating patients with PsA. However, caution is necessary when interpreting the safety findings, as they are supported by evidence of low to very low certainty. Consequently, the balance between benefits and potential risks may change as new safety evaluation studies become available. PROTOCOL REGISTRATION: PROSPERO: CRD42022315577.

Extensive and deep granulomatous ulcers as an atypical manifestation of cartilage-hair hypoplasia syndrome: A diagnostic and therapeutic challenge.

Cartilage hypoplasia syndrome is a primary immunodeficiency disease characterized by short stature, hypoplastic hair and a variable degree of immunodeficiency. Noninfectious cutaneous granulomas represent an uncommon yet well-recognized manifestation within the spectrum of primary immunodeficiency diseases. However, cutaneous granulomas as a manifestation of cartilage-hair hypoplasia syndrome, are extremely rare. We present a case of a middle-aged man with cartilage hypoplasia syndrome featuring cutaneous granulomas, manifesting as chronic, extensive and deep cutaneous ulcers. The patient was treated with anti-TNF-alpha adalimumab with partial improvement. Our case underscores the broad spectrum of clinical manifestations associated with cartilage hypoplasia syndrome and adds new evidence to the potential therapeutic efficacy of anti-TNF-alpha drugs in its treatment.

Expenditure of biological drugs for rheumatoid arthritis treatment in the Brazilian public health system.

OBJECTIVE: This work aims to analyze the quantity and expenses related to biological drugs used for the treatment of rheumatoid arthritis (RA) in outpatient public care within the Brazilian Unified Health System (SUS). METHODS: It is a cross-sectional descriptive study based on secondary data from a historical series, referring to the purchase, volume, and the number of patients treated with different biological drugs (infliximabe, etanercept, adalimumab, rituximab, abatacept, tocilizumab, golimumab, and certolizumab pegol) for RA treatment in outpatient care from 2012 to 2017. The data were extracted from the SUS Outpatient Information System database-SIA/SUS and included ten drugs used for RA treatment. The study assessed the quantity and expenditure of these drugs, the number of RA patients treated, and the expenditure by RA subtypes. The National Broad Consumer Price Index was used to adjust the expenditures for December 2017. RESULTS: The Ministry of Health allocated approximately $500 million to provide about 2 million units of biological drugs for RA patients from 2012 to 2017. The supply of adalimumab 40 mg and etanercept 50 mg accounted for 68.3% of the total expenditure. The subtypes "other rheumatoid arthritis with rheumatoid factor" (ICD-10 M05.8), "rheumatoid arthritis without rheumatoid factor" (ICD-10 M06.0), and "Felty's syndrome" (M05. 0) represented 84.5% of the total expenditures. The proportion of patients treated with biological drugs increased by 33.0%. There was a significant 83.0% increase in the number of patients using biological drugs compared to the overall number of RA patients treated during the study period. CONCLUSIONS: The results obtained allow us to draw a more recent profile of expenditure on RA treatment and indicate trends in the use of biological drugs for this condition, generating data that can support management decisions in public health policies.

Monocyte to high-density lipoprotein cholesterol ratio decreased in patients with psoriasis treated with ixekizumab.

Background: Monocyte to high-density lipoprotein cholesterol ratio (MHR) is a novel inflammatory biomarker which has been associated with cardiovascular diseases. Objective: To study MHR in patients with psoriasis treated with biological agents. Methods: Between April 2019 and August 2022, MHR was retrospectively evaluated in patients with psoriasis before and 3 months after treatment with infliximab, adalimumab, etanercept, ixekizumab, secukinumab, and ustekinumab in a university hospital in Ankara, Turkey. Results: This study included 128 patients, 53 females and 75 males. 39 (30.5%) patients were treated with infliximab, 26 (20.3%) with adalimumab, 8 (6.3%) with etanercept, 18 (14.1%) with ixekizumab, 12 (9.4%) with secukinumab, and 25 (19.5%) with ustekinumab. The median MHR was 0.0127 (0.0086-0.0165) in females and 0.0146 (0.0119-0.0200) in males (p = 0.011). The median MHR decreased after treatment with adalimumab, ixekizumab, secukinumab, and ustekinumab, whereas it increased after treatment with infliximab and etanercept (p = 0.790, p = 0.015, p = 0.754, p = 0.221, p = 0.276, p = 0.889, respectively). Conclusion: MHR significantly decreased in patients with psoriasis after treatment with ixekizumab. Since high MHR levels have been associated with poor clinical outcomes in patients with cardiovascular diseases, ixekizumab might have a positive impact in the treatment of psoriasis patients who had cardiovascular diseases. We suggest that MHR may be useful both in establishing appropriate biological agent treatment and in the follow-up of patients with psoriasis treated with biological agents.

Therapeutic Equivalence of Biosimilar and Reference Biologic Drugs in Rheumatoid Arthritis: A Systematic Review and Meta-analysis.

Importance: Biosimilar drugs are potentially lower-cost versions of biologics that may improve access to therapy. However, there is a lack of adequate systematic reviews demonstrating equivalence between these drugs for the treatment of rheumatoid arthritis (RA). Objectives: To assess the efficacy, safety, and immunogenicity associated with biosimilars of adalimumab, etanercept, and infliximab compared with their reference biologics in patients with RA. Data Sources: MEDLINE via PubMed, Embase, Cochrane Central Register of Controlled Trials, and LILACS databases were searched from inception to September 2021. Study Selection: Head-to-head randomized clinical trials (RCTs) of biosimilars of adalimumab, etanercept, and infliximab and their biologic reference drugs for RA were assessed. Data Extraction and Synthesis: Two authors independently abstracted all data. Meta-analysis was conducted with bayesian random effects using relative risks (RRs) for binary outcomes and standardized mean differences (SMDs) for continuous outcomes, with 95% credible intervals (CrIs) and trial sequential analysis. Specific domains were assessed for the risk of bias in equivalence and noninferiority trials. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline. Main Outcomes and Measures: Equivalence was tested using prespecified margins for the American College of Rheumatology criteria, with at least 20% improvement in the core set measures (ACR20) (ie, RR, 0.94 to 1.06), and for the Health Assessment Questionnaire-Disability Index (HAQ-DI) (ie, SMD, -0.22 to 0.22). Secondary outcomes included 14 items measuring safety and immunogenicity. Results: A total of 25 head-to-head trials provided data on 10 642 randomized patients with moderate to severe RA. Biosimilars met equivalence with reference biologics in terms of ACR20 response (24 RCTs with 10 259 patients; RR, 1.01; 95% CrI, 0.98 to 1.04; τ2 = 0.000) and change of HAQ-DI scores (14 RCTs with 5579 patients; SMD, -0.04; 95% CrI, -0.11 to 0.02; τ2 = 0.002) considering prespecified margins of equivalence. Trial sequential analysis found evidence for equivalence for ACR20 since 2017 and HAQ-DI since 2016. Overall, biosimilars were associated with similar safety and immunogenicity profiles compared with reference biologics. Conclusion and Relevance: In this systematic review and meta-analysis, biosimilars of adalimumab, infliximab, and etanercept were associated with clinically equivalent treatment effects compared with their reference biologics for the treatment of RA.

Eficacia y seguridad de adalimumab en pacientes adultos con artritis reumatoide activa moderada a grave con intolerancia y/o falla a terapia convencional e infliximab / Efficacy and safety of adalimumab in adult patients with moderately to severely active rheumatoid arthritis with intolerance and/or failure to conventional therapy and infliximab

ANTECEDENTES: El presente dictamen expone la evaluación de la eficacia y seguridad de adalimumab en pacientes adultos con artritis reumatoide activa moderada a grave con intolerancia y/o falla a terapia convencional e infliximab. Esta evaluación se realiza en respuesta a la solicitud de la médica especialista en reumatología Ana Karina La Madrid Barreto del Hospital III José Cayetano Heredia de Piura, quien siguiendo la Directiva N° 003-IETSIESSALUD-2016, envió al Instituto de Evaluación de Tecnologías en Salud e Investigación - IETSI la solicitud de autorización de uso del producto farmacéutico adalimumab no incluido en el Petitorio Farmacológico de EsSalud. ASPECTOS GENERALES: La artritis reumatoide (AR) es una enfermedad crónica inflamatoria de etiología desconocida, que inicialmente afecta las articulaciones sinoviales (England 2022; SSR 2021). La AR es una enfermedad típicamente simétrica y, usualmente, si no es ontrolada, ocasiona la destrucción de las articulaciones debido a la erosión del cartílago el hueso, causando deformaciones en

Monoclonal Antibodies for the Treatment of Graves Orbitopathy: Precision Medicine?

PURPOSE: To summarize the development, nomenclature, and rationale of the reported use of monoclonal antibodies (Mabs) in Graves Orbitopathy (GO) and to undertake a systematic review of the management of GO with Mabs. METHODS: The Pubmed and Embase databases and the Federal Brazilian searching site (Periódicos-CAPES) were screened. The authors searched all the keywords "monoclonal antibodies," "adalimumab," "belimumab," "infliximab," "rituximab," "teprotumumab," and "tocilizumab" combined with the terms "Graves Orbitopathy," "Graves eye disease" and "thyroid eye disease." All the articles published in English, French, and Spanish from 2000 to May 2022 were screened. Only publications with quantitative data on the activity of orbitopathy, proptosis, or both were included. RESULTS: Seventy-six articles of the 954 screened records met the inclusion criteria. Seven Mabs were described for treating GO. The three most reported Mabs were Rituximab, Tocilizumab, and Teprotumumab. Only eight randomized clinical trials compared the effect of these three Mabs and Belimumab with the effect of steroids or placebos. Adalimumab, Infliximab, and K1-70 only appeared in a few case series and case reports. Frequent mild-to-moderate and few major side effects occurred with the three most used Mabs. Relapse rates ranged from 7.4% for Tocilizumab to at least 29.4% for Teprotumumab. No randomized clinical trials compared Mabs head-to-head. CONCLUSION: Considering the lack of head-to-head comparisons between Mabs, the relapse rate, the possibility of severe collateral effects, and the cost of Mabs, it is not clear which Mab is the safest and most useful to treat GO.

Impact of initial therapy with upadacitinib or adalimumab on achievement of 48-week treatment goals in patients with rheumatoid arthritis: post hoc analysis of SELECT-COMPARE.

OBJECTIVES: Evaluate the importance of treatment sequencing in SELECT-COMPARE, assessing potential differences between starting upadacitinib or adalimumab therapy following inadequate MTX response. METHODS: Patients from SELECT-COMPARE were randomized to upadacitinib 15 mg once daily, placebo or adalimumab 40 mg. Per protocol, patients with <20% improvement in tender or swollen joint counts (weeks 14, 18, 22) or failure to achieve Clinical Disease Activity Index (CDAI) low disease activity (LDA) at week 26 were blindly switched from upadacitinib to adalimumab or vice versa. Treatment outcomes, including clinical remission/LDA, physical function, pain and a novel combined endpoint for deep response, were evaluated through 48 weeks and corresponding time-averaged response rates determined. Data were analysed by initial randomized group regardless of any subsequent switch in therapy. RESULTS: This post hoc analysis included 651 patients initially randomized to upadacitinib (of whom 252 switched to adalimumab) and 327 patients initially randomized to adalimumab (of whom 159 switched to upadacitinib). At week 48, patients randomized to either therapy demonstrated similar achievement of most treatment endpoints. Greater improvements in the total time spent in a lower disease state were observed for initial upadacitinib vs initial adalimumab therapy across most clinical and patient-reported outcomes through 48 weeks, and the median time to DAS28(CRP) <2.6/≤3.2 occurred 6-8 weeks earlier among those randomized to upadacitinib. CONCLUSION: Following a modified treat-to-target strategy, rates of CDAI remission/LDA and DAS28(CRP) <2.6/≤3.2 at 48 weeks were similar, regardless of starting therapy. However, patients initially receiving upadacitinib reached treatment targets more quickly and spent more time in clinical targets over the initial 48 weeks of treatment. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT02629159.

Vedolizumabe comparado a agentes anti-TNF-α para indução e manutenção da remissão na doença de Crohn refratária a medicamentos biológicos: revisão rápida / Vedolizumab compared to anti-tnf-α agents for induction and maintenance of remission in biologic-refractory crohn's disease: a rapid review of systematic reviews

Vedolizumabe e anticorpos anti-TNF-α (infliximabe, adalimumabe, certolizumabe pegol). Indicação: Tratamento pessoas com doença de Crohn com falha a um agente biológico anti-TNF-α em tratamento prévio. Pergunta: Para adultos com doença de Crohn moderada a grave com falha terapêutica para anticorpos monoclonais anti-TNF-α, em tratamento de segunda linha, Vedolizumabe tem efeitos superiores aos anti-TNF-α para induzir e manter a remissão da doença? Objetivo: Investigar a eficácia e segurança do vedolizumabe, comparado aos agentes anti-TNF-α (infliximabe, adalimumabe, certolizumabe pegol), na indução e manutenção da remissão em pacientes refratários aos anti-TNF-α com doença de Crohn moderada a grave. Métodos: Revisão rápida de revisões sistemáticas. Levantamento bibliográfico foi realizado nas bases de dados PUBMED, EMBASE, SCOPUS, BVS, Cochrane Library e em registros de revisões sistemáticas e ensaios clínicos. Seguiu estratégias de buscas predefinidas. Foi feita avaliação da qualidade metodológica dos estudos incluídos através da ferramenta AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews Version) Resultados: Foi selecionada uma revisão sistemática, que atendida aos critérios de elegibilidade, mas nenhum ensaio clínico foi escolhido, pois não atendiam aos critérios de inclusão. Conclusão: Adalimumabe, disponível no Sistema Único de Saúde, é mais eficaz que vedolizumabe para induzir remissão clínica em pacientes tratados previamente com biológicos. Vedolizumabe não é mais eficaz que placebo para induzir remissão clínica. Vedolizumabe e adalimumabe são similares entre si e são mais eficazes que placebo para manter a remissão clínica. Não foram encontradas evidências comparando vedolizumabe a infliximabe ou certolizumabe pegol

Vedolizumab and anti-TNF-α antibodies (infliximab, adalimumab, certolizumab pegol). Indication: Treatment of people with Crohn disease who have failed an anti-TNF-α biological agent in previous treatment. Question: For adults with moderate to severe Crohn disease with treatment failure for anti-TNF-α monoclonal antibodies, in second-line treatment, does vedolizumab have superior effects to anti-TNF-α in inducing and maintaining disease remission? Objective: To investigate the efficacy and safety of vedolizumab, compared to anti-TNF-α agents (infliximab, adalimumab, certolizumab pegol), in the induction and maintenance of remission in moderate to severe Crohn disease refractory to anti-TNF-α previous treatment. Methods: Rapid review of systematic reviews. A bibliographic search was done in the PUBMED, EMBASE, SCOPUS, BVS, Cochrane Library databases and in registries of systematic reviews and clinical trials. The search has followed predefined strategies. The methodological quality of the included studies was evaluated using the AMSTAR-2 tool (Assessing the Methodological Quality of Systematic Reviews Version 2). Results: A systematic review was selected, which met the eligibility criteria, but no clinical trials were chosen as they did not meet the inclusion criteria. Conclusion: Adalimumab, available in the Brazilian Public Health System, is more effective than vedolizumab to induce clinical remission in patients previously treated with biologics. Vedolizumab is no more effective than placebo in inducing clinical remission. Vedolizumab and adalimumab are similar to each other and are more effective than placebo in maintaining clinical remission. No evidence was found comparing vedolizumab to infliximab or certolizumab pegol

Optical coherence tomography changes in ankylosing spondylitis patients on long-term adalimumab treatment.

OBJECTIVE: Long-term ocular effects of tumor necrosis factor-alpha inhibitors remain to be elucidated. This study aimed to examine the long-term effects of adalimumab use on neural tissue of the anterior visual pathways using optical coherence tomography in patients with ankylosing spondylitis. METHODS: This was a single-center, open-label, cross-sectional study conducted at the Giresun University Faculty of Medicine, Physical Medicine and Rehabilitation Department, between November 2019 and August 2020. This study included 26 ankylosing spondylitis patients receiving adalimumab for at least 1 year and 21 healthy controls. All subjects underwent a full ophthalmological examination and optical coherence tomography examination with the following measurements: peripapillary retinal nerve fiber layer thickness, peripapillary retinal thickness, peripapillary choroidal thickness, ganglion cell complex thickness, and the optic head properties. RESULTS: Peripapillary retinal nerve fiber layer thickness and retinal thickness measurements were lower in the adalimumab group. In addition, ganglion cell complex thickness was significantly lower and the cup-to-disc ratio was significantly higher in the adalimumab group (p<0.05). However, the two groups did not differ in terms of peripapillary choroidal thickness and disc area (p>0.05). CONCLUSION: Although tumor necrosis factor-alpha inhibitors have some favorable effects on the ocular involvement of patients with ankylosing spondylitis, they may also have paradoxical detrimental effects as evidenced by structural changes observed by optical coherence tomography. Future studies with better design, probably including a large number of patients with a range of rheumatological diseases and tumor necrosis factor-alpha inhibitors, are warranted.

Uveitis and nail psoriasis in a patient without articular involvement: a case report.

BACKGROUND: This study aimed to report a case of bilateral anterior non-granulomatous chronic non-infectious uveitis associated with isolated nail psoriasis without articular involvement. CASE PRESENTATION: A 55-year-old man with a history of open-angle glaucoma was referred to our uveitis and ocular immunology center with intraocular inflammation concordant with chronic non-infectious bilateral anterior non-granulomatous uveitis. At presentation, he had moderate inflammation in the anterior chamber bilaterally and lesions characteristic of nail psoriasis. Nail psoriasis was later confirmed by nail ultrasonography performed by a radiologist who specialized in psoriasis. Appropriate clinical and paraclinical assessments were conducted, ruling out all other possible causes of uveitis. The patient required dual systemic immunomodulatory therapy with methotrexate and adalimumab, topical anti-inflammatory drugs (steroidal and non-steroidal), and anti-glaucoma therapy to achieve satisfactory inflammatory and ocular pressure control. DISCUSSION AND CONCLUSIONS: This is the first report of non-infectious uveitis associated with nail compromise in a patient without other manifestations of psoriasis. Despite reports on the relationship between psoriatic disease and uveitis, there is insufficient information on clinical phenotypes associated with uveitis that could lead to later diagnosis and treatment of associated intraocular inflammation. Clinicians should be aware of all subtypes of psoriasis that increases a risk of developing uveitis in these patients.

First-line biologic therapy with tumor necrosis factor inhibitors for psoriatic arthritis: a prospective observational study.

BACKGROUND: Psoriatic arthritis (PsA) is a chronic inflammatory disease that affects multiple joints. It is associated with psoriasis and treated with synthetic and biologic drugs. OBJECTIVE: The objective of this study was to assess the outcomes of patients who received biologic therapy with tumor necrosis factor (TNF) inhibitors in terms of effectiveness, safety, functionality, and quality of life. DESIGN AND SETTING: A prospective observational study was performed at a single center in Belo Horizonte, Brazil. METHODS: Patients with PsA who received their first TNF inhibitor treatment were followed up for 12 months. Disease activity was measured using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Clinical Disease Activity Index (CDAI). Functionality was measured using the Health Questionnaire Assessment (HAQ), and quality of life was evaluated using the European Quality of Life Five Dimensions (EQ-5D). Multiple linear regression was used to identify predictors of the clinical response at 12 months. RESULTS: A total of 143 patients treated with adalimumab or etanercept were evaluated. Most of the clinical measures were significantly improved at 12 months. However, 31%-51% of the patients did not achieve good clinical control. No differences were observed between adalimumab and etanercept, except for poor functionality at 12 months among patients treated with etanercept. The main predictors of a worse clinical response were female sex, etanercept use, poor functionality, or lower quality of life at baseline. The main adverse reactions were alopecia, headache, injection site reaction, sinusitis, flu, dyslipidemia, and infections. CONCLUSION: TNF inhibitor therapy was effective and safe. However, despite improvements in clinical measures, most patients did not achieve satisfactory control of the disease.

Update of the PANCCO clinical practice guidelines for the treatment of ulcerative colitis in the adult population.

Ulcerative colitis (US) is a chronic disease of unknown etiology. It is incurable and its clinical course is intermittent, characterized by periods of remission and relapse. The prevalence and incidence of the disease has been increasing worldwide. The update presented herein includes the participation of healthcare professionals, decision-makers, and a representative of the patients, all of whom declared their conflicts of interest. Answerable clinical questions were formulated, and the outcomes were graded. The information search was conducted on the Medline/PubMed, Embase, Epistemonikos, and LILACS databases, and covered grey literature sources, as well. The search was updated on November 30, 2020, with no restrictions regarding date or language. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) classification system was implemented to establish the strength of the recommendation and quality of evidence. A formal consensus was developed, based on the RAND/UCLA methodology and the document was peer reviewed. The short version of the Clinical Practice Guidelines for the Treatment of Ulcerative Colitis in the Adult Population is presented herein, together with the supporting evidence and respective recommendations. In mild-to-moderate UC, budesonide MMX is an option when treatment with 5-ASA fails, and before using systemic steroids. In moderate-to-severe UC, infliximab, adalimumab, vedolizumab, ustekinumab, and tofacitinib can be used as first-line therapy. If there is anti-TNF therapy failure, ustekinumab and tofacitinib provide the best results. In patients with antibiotic-refractory pouchitis, anti-TNFs are the treatment of choice.

Anti-TNF therapy for ulcerative colitis in Brazil: a comparative real-world national retrospective multicentric study from the Brazilian study group of IBD (GEDIIB).

BACKGROUND: Anti-TNF therapy represented a landmark in medical treatment of ulcerative colitis (UC). There is lack of data on the efficacy and safety of these agents in Brazilian patients. The present study aimed to analyze rates of clinical and endoscopic remission comparatively, between adalimumab (ADA) and infliximab (IFX), in Brazilian patients with UC, and evaluate factors associated with clinical and endoscopic remission after 1 year of treatment. METHODS: A national retrospective multicenter study (24 centers) was performed including patients with UC treated with anti-TNF therapy. Outcomes as clinical response and remission, endoscopic remission and secondary loss of response were measured in different time points of the follow-up. Baseline predictive factors of clinical and endoscopic remission at week 52 were evaluated using logistic regression model. Indirect comparisons among groups (ADA and IFX) were performed using Student's t, Pearson χ2 or Fisher's exact test when appropriated, and Kaplan Meier analysis. RESULTS: Overall, 393 patients were included (ADA, n = 111; IFX, n = 282). The mean age was 41.86 ± 13.60 years, 61.58% were female, most patients had extensive colitis (62.40%) and 19.39% had previous exposure to a biological agent. Overall, clinical remission rate was 66.78%, 71.62% and 82.82% at weeks 8, 26 and 52, respectively. Remission rates were higher in the IFX group at weeks 26 (75.12% vs. 62.65%, p < 0.0001) and 52 (65.24% vs. 51.35%, p < 0.0001) when compared to ADA. According to Kaplan-Meier survival curve loss of response was less frequent in the Infliximab compared to Adalimumab group (p = 0.001). Overall, endoscopic remission was observed in 50% of patients at week 26 and in 65.98% at week 52, with no difference between the groups (p = 0.114). Colectomy was performed in 23 patients (5.99%). Age, non-prior exposure to biological therapy, use of IFX and endoscopic remission at week 26 were associated with clinical remission after 52 weeks. Variables associated with endoscopic remission were non-prior exposure to biological therapy, and clinical and endoscopic remission at week 26. CONCLUSIONS: IFX was associated with higher rates of clinical remission after 1 year in comparison to ADA. Non-prior exposure to biological therapy and early response to anti-TNF treatment were associated with higher rates of clinical and endoscopic remission.

Adalimumab para espondilitis anquilosante / Adalimumab for ankylosing spondylitis

INTRODUCCIÓN: La EA es una forma crónica de artritis de origen desconocido que forma parte del grupo de las espondiloartritis. Este último comprende un conjunto de enfermedades inflamatorias que se caracterizan por el compromiso de las articulaciones sacroilíacas y de la columna. 1 En la EA predomina el compromiso de la columna o axial, existiendo un cierto grado de daño estructural visible en la radiografía simple (a diferencia de la espondiloartritis axial no radiológica en la cual no se observa compromiso en la radiografía simple), y con frecuencia progresa hacia anquilosis de las articulaciones afectadas. A su vez, hasta la mitad de los pacientes con EA presentan compromiso articular periférico, principalmente de grandes articulaciones como caderas y rodillas. Puede acompañarse de manifestaciones extra articulares, como la uveítis, o de enfermedades asociadas, como la enfermedad inflamatoria intestinal. Es una enfermedad discapacitante con un gran impacto en la productividad laboral y la calidad de vida de los pacientes; acarreando un aumento en los costos directos e indirectos tanto para el paciente, como para la sociedad. OBJETIVO: El objetivo del presente informe es evaluar la eficacia, seguridad, recomendaciones, políticas de cobertura y aspectos económicos de adalimumab para espondilitis anquilosante. MÉTODOS: Se buscó en los sitios públicos de Pubmed, LILACS, BRISA/REDETSA-, CRD (del inglés, Centre for Reviews and Dissemination- University of York), Cochrane; en "buscadores genéricos de internet" y sociedades científicas. En lo que respecta a agencias de ETS, se buscó en: Base de datos internacional para las ETS de INHATA (su sigla del inglés, International Network of Agencies for Health Technology Assessment), Base Regional de Informes de Evaluación de Tecnologías en Salud de las Américas (BRISA), y en agencias como NICE (del inglés, National Institute for Health and Clinical Excellence) del Reino Unido; PBAC (del inglés, The Pharmaceutical Benefits Advisory Committee) de Australia; CADTH (del inglés, Canadian Agency for Drugs and Technologies in Health) de Canadá y CONITEC (del portugués, Comissão Nacional de Incorporação de Tecnologías no SUS) de Brasil. RESULTADOS: No se encontraron estudios que comparen en forma directa al adalimumab con otros agentes biológicos en pacientes con EA activa a pesar de la terapia habitual (AINES). Evidencia de alta calidad muestra que adalimumab, en pacientes con EA activa y respuesta inadecuada o intolerancia a la terapia habitual, es superior al placebo más terapia habitual en el control de la actividad de la enfermedad, medida a través de escalas clínicas validadas. Los resultados del estudio de extensión abierto, a cinco años, son consistentes con los de los ensayos clínicos. Evidencia de baja calidad, proveniente de comparaciones indirectas, sugiere que adalimumab sería similar a otros agentes biológicos en esta indicación. Las guías de práctica clínica consideran al adalimumab como una de las alternativas de tratamiento en esta población de pacientes y recomiendan considerar la presencia de manifestaciones extra articulares para la elección del tratamiento. Los financiadores de salud públicos y privados de Europa y Estados Unidos relevados, prestan cobertura a este y otros fármacos biológicos para esta indicación, sin recomendar uno por sobre el otro. La mayoría de las políticas de cobertura de América Latina relevadas, cubren al adalimumab en EA y el mismo se encuentra en el Sistema Único de Recupero (SUR) de la Superintendencia de Servicios de Salud de Argentina. Algunas guías y políticas de cobertura afirman que en caso de que más de un fármaco sea adecuado, deben contemplarse los costos en la selección. Los resultados del análisis de impacto presupuestario acumulado a tres años, bajo los supuestos asumidos, en pacientes con respuesta inadecuada a AINES, muestran que la tecnología generaría ahorros. CONCLUSIONES: No se encontraron estudios que comparen en forma directa al adalimumab con otros agentes biológicos en pacientes con espondilitis anquilosante activa a pesar de la terapia habitual (anti inflamatorios no esteroideos). Evidencia de alta calidad muestra que adalimumab, en pacientes con espondilitis anquilosante activa y respuesta inadecuada o intolerancia a la terapia habitual, es superior al placebo más terapia habitual en el control de la actividad de la enfermedad, medida a través de escalas clínicas validadas. Los resultados del estudio de extensión abierto, a cinco años, son consistentes con los de los ensayos clínicos. Evidencia de baja calidad, proveniente de comparaciones indirectas, sugiere que adalimumab sería similar a otros agentes biológicos en esta indicación, a excepción del upadacitinib donde no se halló evidencia comparativa. Las guías de práctica clínica consideran al adalimumab como una de las alternativas de tratamiento en esta población de pacientes y recomiendan considerar la presencia de manifestaciones extra articulares para la elección del tratamiento. Los financiadores de salud públicos y privados de Europa y Estados Unidos relevados, prestan cobertura a este y otros fármacos biológicos para esta indicación, sin recomendar uno por sobre otro. La mayoría de las políticas de cobertura de América Latina relevadas, cubren al adalimumab en espondilitis anquilosante y el mismo se encuentra en el Sistema Único de Recupero (SUR) de la Superintendencia de Servicios de Salud de Argentina. Algunas guías y políticas de cobertura afirman que en caso de que más de un fármaco sea adecuado, deben contemplarse los costos en la selección. Los resultados del análisis de impacto presupuestario acumulado en los próximos tres años, bajo los supuestos asumidos, en pacientes con respuesta inadecuada a anti inflamatorios no esteroideos, muestran que la tecnología generaría ahorros.

Treating the skin with biologics in patients with psoriasis decreases the incidence of psoriatic arthritis.

OBJECTIVES: To compare the incidence of psoriatic arthritis (PsA) in patients with psoriasis (PsO) according to different treatments for their skin: topics/no treatment, conventional disease-modifying antirheumatic drugs (DMARDs) (cDMARDs) or biological DMARDs (bDMARDs). METHODS: Patients with PsO without PsA followed at a university hospital were included in this retrospective cohort study. Patients were classified according to their treatment in topics (topics, phototherapy or no treatment), cDMARDs (methotrexate and cyclosporine) and bDMARDs (tumour necrosis factor inhibitors (TNFi), interleukin 17 inhibitors (IL-17i) and IL-12-23i ((interleukin (IL) 12/IL-23 inhibitor))) groups. Incident cases of PsA were attributed to one treatment if developed during the administration of that treatment. A Cox proportional hazards model was used to evaluate the adjusted risk of PsA development by treatment group. RESULTS: 1719 patients with PsO contributed a total of 14 721 patient/years (py). 1387 (81%) patients were in the topics, 229 (13%) in cDMARDs and 103 (6%) in the bDMARDs group. During follow-up, 239 patients (14%) developed PsA (231 under topics, six under cDMARDs and two under bDMARDs). Global incidence was 1.6 per 100 py. The risk of developing PsA in patients with PsO treated with bDMARDs was significantly lower (incidence rate ratio (IRR)=0.26; 95% CI 0.03 to 0.94; p=0.0111), compared with topics, but not compared with cDMARDs (IRR=0.35; 95% CI 0.035 to 1.96; p=0.1007). Adjusted Cox proportional hazards regression analysis showed that male sex, nail involvement and higher body max index were associated with increased risk of developing PsA, while biologics use was protective (HR: 0.19; 95% CI 0.05 to 0.81). CONCLUSION: Treatment with biologics in patients with PsO reduced the risk of PsA development.

Economic evaluation of adalimumab versus etanercept for psoriatic arthritis in a Brazilian real-world model.

BACKGROUND: TNF inhibitors are costly drugs supplied generally on health systems or private insurances. Performance analysis is essential to verify the results achieved by health technologies in these systems. The objective of the study was to compare the two most used biological drugs for the treatment of psoriatic arthritis (PsA) in Brazil. METHODS: A cost-utility analysis was built using a Markov model, with a five-year time horizon, a discount rate of 5%, and from the perspective of the Unified Health System. Deterministic and probabilistic sensitivity analyses were performed. RESULTS: Etanercept was the most cost-effective drug. Adalimumab became the most cost-effective drug in one of the four analysis scenarios with a willingness to pay from one gross domestic product per capita. The deterministic sensitivity analysis identified that the cost parameters had the greatest impact on the most effective drug. The probabilistic sensitivity analysis indicated that etanercept is the drug most likely to be cost-effective. CONCLUSION: The difference between the drugs in terms of utility was minimal and the costs were the main factor that impacted the cost-utility ratio, which points to the benefits of price renegotiation for the efficient allocation of resources in the health system.