-
Zeitschrift Fur Rheumatologie Jun 2024Head-to-head studies are important to select the optimal treatment in terms of efficacy and side effect profiles when several drugs are available. (Review)
Review
BACKGROUND
Head-to-head studies are important to select the optimal treatment in terms of efficacy and side effect profiles when several drugs are available.
AIM OF THE WORK
This article describes all studies comparing the use of disease-modifying antirheumatic drugs (DMARD) in rheumatoid arthritis (RA) in head-to-head studies or in which a DMARD was at least included in an active comparison arm.
RESULTS
A total of 23 studies comparing DMARDs were identified. These included comparisons of Janus kinase (JAK) inhibitors with methotrexate and with adalimumab as well as the oral surveillance study.
DISCUSSION
There are already an exceptionally large number of head-to-head studies in RA, both for comparisons of efficacy and safety of DMARDs. Nevertheless, more such comparative studies are needed, for example to clarify whether adverse events of tofacitinib observed in the oral surveillance study are specific to the JAK 1/JAK 3 inhibitor or are a class effect of all JAK inhibitors.
PubMed: 38831141
DOI: 10.1007/s00393-024-01517-8 -
Ocular Immunology and Inflammation Jun 2024To investigate the long-term efficacy and safety of adalimumab(ADA) in the treatment of patients with serpiginous choroiditis (SC) refractory to conventional therapy...
BACKGROUND/OBJECTIVES
To investigate the long-term efficacy and safety of adalimumab(ADA) in the treatment of patients with serpiginous choroiditis (SC) refractory to conventional therapy through quantitative parameters.
SUBJECTS/METHODS
A retrospective analysis was conducted on patients diagnosed with SC clinically and through fundus autofluorescence(FAF). Patients receiving ADA treatment were included. Demographic and clinical characteristics of the patients, association with tuberculosis (TB) infection, number of immunosuppressive therapies, recurrences, best corrected visual acuity (BCVA) change, and ADA-related side effects were recorded. The progression rate before and after ADA was calculated based on the area involved by FAF.
RESULTS
Sixteen eyes of 8 patients (3 female/5 male) were enrolled to the study. The median (IQR) age was 53.5 (16.5) years. Diagnosis was SC in 4, ampiginous choroiditis in 3, and TB-related serpiginous-like choroiditis in 1 patient. Peripapillary involvement was present in 10 of 16 eyes. The area involved by FAF continued to progress under ADA treatment, however the progression rate was decreased ( = 0.143).The BCVA was preserved ( = 0.772). The number of systemic and local treatments decreased with ADA ( = 0.025 and 0.019, respectively). Additionally, the number of recurrences was reduced with ADA ( = 0.002). Median (IQR) follow-up was 45(28.75) months. Two patients experienced ADA-related side effects (pulmonary TBand rash).
CONCLUSIONS
Our findings suggest a promising role for ADA in halting the progression of SC and have implications for improving outcomes. Despite the evidence in the literature at the level of case reports, ADA can be used effectively with close monitoring for potential risks.
PubMed: 38829969
DOI: 10.1080/09273948.2024.2359002 -
Therapeutic Advances in Gastroenterology 2024Anti-tumor necrosis factor (TNF) monoclonal antibodies, especially infliximab (IFX) and adalimumab (ADA), are considered the first-line treatment for active Crohn's...
Development and validation of a novel therapeutic drug monitoring-based nomogram for prediction of primary endoscopic response to anti-TNF therapy in active Crohn's disease.
BACKGROUND
Anti-tumor necrosis factor (TNF) monoclonal antibodies, especially infliximab (IFX) and adalimumab (ADA), are considered the first-line treatment for active Crohn's disease (CD). However, the predictive role of therapeutic drug monitoring (TDM) of serum anti-TNF in monitoring the treatment of inflammatory bowel disease (IBD) remains controversial.
OBJECTIVES
To explore the correlation between serum anti-TNF levels and early endoscopic response in active CD using a TDM-based nomogram.
DESIGN
Cross-sectional study.
METHODS
The simplified endoscopic activity score for CD (SES-CD), Crohn's disease activity index (CDAI), laboratory parameters, and the serum trough levels of IFX and ADA were assessed.
RESULTS
The trough levels of IFX or ADA were significantly higher in patients with endoscopic response compared to non-responders in the development cohort ( < 0.001). The IFX and ADA levels showed a weak but significantly negative correlation with SES-CD ( < 0.001), CDAI ( < 0.001), and C-reactive protein (CRP) ( < 0.001) at week 14 post-IFX therapy in the development cohort. Furthermore, the receiver operating characteristic curve revealed that an optimal level of IFX (4.80 μg/mL) and ADA (8.80 μg/mL) exhibited the best performance in predicting endoscopic response. Concomitantly, we developed a novel nomogram prediction model based on the results of multivariate logistic regression analysis, which consisted of CRP, albumin (Alb), and anti-TNF trough levels at week 14. The nomogram showed significant discrimination and calibration for both IFX and ADA in the development cohort and performed well in the external validation cohort.
CONCLUSION
This study demonstrates a robust association between serum concentrations of IFX, ADA, Alb, and CRP and primary endoscopic response in active CD patients. Importantly, the TDM- and laboratory marker-based nomogram may be used to evaluate the primary endoscopic response to anti-TNF therapy, especially for optimizing treatment strategies and switching therapy in CD patients.
PubMed: 38827646
DOI: 10.1177/17562848241256237 -
Therapeutic Advances in Chronic Disease 2024Hidradenitis suppurativa (HS) is an inflammatory skin condition with an underlying inflammatory process. Due to the limited efficacy of available treatments, HS remains... (Review)
Review
Hidradenitis suppurativa (HS) is an inflammatory skin condition with an underlying inflammatory process. Due to the limited efficacy of available treatments, HS remains a therapeutic challenge. The safety and efficacy of tumor necrosis factor-α (TNF-α) inhibitors, adalimumab, infliximab, and etanercept, are well studied in this patient population, and in some cases, HS was unresponsive to them. In recent years, evidence has been growing regarding the application of other anti-TNFs, including certolizumab pegol (CPZ) and golimumab. We sought to evaluate the overall safety and efficacy of golimumab and CPZ in the management of HS. A comprehensive search was performed on the PubMed, Scopus, Web of Science, and Ovid Embase databases, as well as the Google Scholar search engine from initiation to 31 August 2023. A total of nine and four studies used CPZ and golimumab to treat HS, respectively. Individuals with concomitant inflammatory immune-mediated diseases, pregnant females, and patients who were refractory to previous treatments achieved a Hidradenitis Suppurativa Clinical Response following CPZ administration. Also, golimumab showed promise in treating recalcitrant HS after the failure of other treatments, such as adalimumab and anti-interleukin-1. CPZ and golimumab can be efficacious treatment options for moderate-to-severe HS, especially in patients who are unresponsive to other TNF inhibitors, such as adalimumab.
PubMed: 38827348
DOI: 10.1177/20406223241257342 -
Therapeutic Advances in Musculoskeletal... 2024The aim of the Severe Psoriatic arthritis - Early intervEntion to control Disease trial is to compare outcomes in psoriatic arthritis (PsA) patients with poor prognostic...
The protocol of a clinical effectiveness trial comparing standard step-up care, early combination DMARD therapy and early use of TNF inhibitors for the treatment of moderate to severe psoriatic arthritis: the 3-arm parallel group SPEED randomized controlled trial.
OBJECTIVES
The aim of the Severe Psoriatic arthritis - Early intervEntion to control Disease trial is to compare outcomes in psoriatic arthritis (PsA) patients with poor prognostic factors treated with standard step-up conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), combination csDMARDs or a course of early biologics.
DESIGN
This multicentre UK trial was embedded within the MONITOR-PsA cohort, which uses a trial within cohort design.
METHODS AND ANALYSIS
Patients with newly diagnosed PsA and at least one poor prognostic factor (polyarthritis, C-reactive protein >5 mg/dL, health assessment questionnaire >1, radiographic erosions) were randomized equally and open-label to either standard care with 'step-up' csDMARD therapy, initial therapy with combination csDMARDs (methotrexate with either sulfasalazine or leflunomide) or to early biologics induction therapy (adalimumab plus methotrexate). The primary outcome is the PsA disease activity score at week 24.
ETHICS
Ethical approval for the study was granted by the South Central Research Ethics Committee (ref 18/SC/0107).
DISCUSSION
Treatment recommendations for PsA suggest more intensive therapy for those with poor prognostic factors but there are no studies that have previously used prognostic factors to guide therapy. Applying initial intensive therapy has shown improved outcomes in other inflammatory arthritides but has never been tried in PsA. Combination csDMARDs have shown some superiority over single therapies but there are limited data and concerns about side effects. Early use of biologics has also been shown to be superior to methotrexate but these drugs are costly and not usually funded first line. However, if a short course of biologics can rapidly suppress inflammation allowing treatment to be withdrawn and response maintained on methotrexate, this may be a cost-effective model for early use.
TRIAL REGISTRATION
ClinicalTrials.gov (NCT03739853) and EudraCT (2017-004542-24).
PubMed: 38826570
DOI: 10.1177/1759720X241240913 -
The Journal of Rheumatology Jun 2024To analyze the long-term survival of subcutaneous biosimilar TNFα-inhibitors (TNFi) compared to the originator molecules in patients with rheumatic diseases, and the...
OBJECTIVE
To analyze the long-term survival of subcutaneous biosimilar TNFα-inhibitors (TNFi) compared to the originator molecules in patients with rheumatic diseases, and the factors associated with drug discontinuation.
METHODS
Retrospective analysis of BIOBADASER, the Spanish multicenter prospective registry of rheumatic patients on biological and targeted disease-modifying anti-rheumatic drugs. Patients who started etanercept or adalimumab from January 2016 to October 2023 were included. The survival probabilities of biosimilars and originators were compared using Kaplan-Meier estimating curves. To identify factors associated with differences in the retention rates, hazard ratios (HR) were estimated using Cox regression models for all and specific (inefficacy or adverse events) causes of discontinuation.
RESULTS
A total of 4162 patients received 4723 treatment courses (2991 courses of adalimumab and 1732 courses of etanercept), of which 722 (15.29%) were originator molecules and 4001 (84.71%) biosimilars. The originators were more frequently discontinued than biosimilars (53.32% and 33.37%, respectively). The main reason for discontinuation was inefficacy (60.35% of the treatments). The risk of overall discontinuation was lower for biosimilars (adjusted HR 0.84, 95% CI: 0.75-0.95). Female sex, obesity and second or later treatment lines increased the risk of discontinuation, while disease duration and the use of concomitant methotrexate were associated to a greater survival. When assessing cause-specific reasons of discontinuation, excluding nonmedical switching, the results from the crude and adjusted analyses showed no significant differences in the retention rate between biosimilars and originators.
CONCLUSION
No significant differences were found between treatmens in the longterm survival due to inefficacy or adverse events.
PubMed: 38825358
DOI: 10.3899/jrheum.2024-0001 -
Journal of Managed Care & Specialty... Jun 2024Congress passed the Biologic Price Competition and Innovation Act of 2009, specifically to offer market competition as a counterweight to the rising costs of biologic...
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.
Topics: Biosimilar Pharmaceuticals; Humans; United States; Economic Competition; Drug Costs; United States Food and Drug Administration; Adalimumab; Insurance, Pharmaceutical Services; Drug Approval
PubMed: 38824633
DOI: 10.18553/jmcp.2024.30.6.600 -
The British Journal of Dermatology May 2024Primary endpoint measures in clinical trials are typically measures of disease severity, with patient reported outcome measures (PROMs) relegated as secondary endpoints....
BACKGROUND
Primary endpoint measures in clinical trials are typically measures of disease severity, with patient reported outcome measures (PROMs) relegated as secondary endpoints. However validation of some PROMs may be more rigorous than that of disease severity measures, arguing for a primary role for PROMs.
OBJECTIVES
This study reports on 24 peer reviewed journal articles that used the Dermatology Life Quality Index (DLQI) as primary outcome, derived from a systematic review of randomised controlled trials (RCTs) utlising DLQI covering all diseases and interventions.
MATERIALS AND METHOD
The study protocol was prospectively published on the PROSPERO database, and the study followed PRISMA guidelines. Searches were made with Medline, Cochrane library, EMBASE, Web of Science, SCOPUS, CINAHL(EBSCO) and PsycINFO databases and records combined into an Endnote database. Records were filtered for duplicates and selected by study inclusion/exclusion criteria. Full text articles were sourced and data was extracted by two reviewers into a bespoke REDCap database, with a third reviewer adjudicating differences. The Jadad scoring method was used to determine risk of bias.
RESULTS
Of the 3,220 publications retrieved from online searching, 457 articles met eligibility criteria and included 198,587 patients. DLQI scores were primary outcomes in 24 (5.3%) of these studies comprising 15 different diseases and 3,436 patients. Most study interventions (17/24 studies, 68%) were systemic drugs with biologics (liraglutide, alefacept, secukinumab, ustekinumab, adalimumab) accounting for five out of 25 pharmacological interventions (20%). Topical treaments comprised 32% (8 studies) whereas non-pharmacological interventions (8) were 24% of the total interventions (33). Three studies used non-traditional medicines. Eight studies were multicentred (33.3%), with trials conducted in at least 14 different countries, and four (16.7%) were conducted in multiple countries. The Jadad risk of bias scale showed that bias was uncertain or low, as 87.5% of studies had Jadad scores of ≥3.
CONCLUSIONS
This study provides evidence for use of the DLQI as primary outcome in clinical trials to inform researchers' and clinicians' decisions for its further use.
PubMed: 38819233
DOI: 10.1093/bjd/ljae228 -
RMD Open May 2024To compare the effectiveness of a strategy administering baricitinib versus one using TNF-inhibitors (TNFi) in patients with rheumatoid arthritis (RA) after conventional... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
PERFECTRA: a pragmatic, multicentre, real-life study comparing treat-to-target strategies with baricitinib versus TNF inhibitors in patients with active rheumatoid arthritis after failure on csDMARDs.
OBJECTIVE
To compare the effectiveness of a strategy administering baricitinib versus one using TNF-inhibitors (TNFi) in patients with rheumatoid arthritis (RA) after conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) failure in a real-life treat-to-target (T2T) setting.
METHODS
Patients with biological and targeted synthetic DMARD (b/tsDMARD) naïve RA with disease duration ≤5 years without contraindications to b/tsDMARD were randomised to either TNFi or baricitinib when csDMARD failed to achieve disease control in a T2T setting. Changes in clinical and patient-reported outcome measures (PROMs) were assessed at 12-week intervals for 48 weeks. The primary endpoint was non-inferiority, with testing for superiority if non-inferiority is demonstrated, of baricitinib strategy in the number of patients achieving American College of Rheumatology 50 (ACR50) response at 12 weeks. Secondary endpoints included 28-joint count Disease Activity Score with C reactive protein (DAS28-CRP) <2.6, changes in PROMs and radiographic progression.
RESULTS
A total of 199 patients (TNFi, n=102; baricitinib, n=97) were studied. Both study groups were similar. Baricitinib was both non-inferior and superior in achieving ACR50 response at week 12 (42% vs 20%). Moreover, 75% of baricitinib patients achieved DAS28-CRP <2.6 at week 12 compared with 46% of TNFi patients. On secondary outcomes throughout the duration of the study, the baricitinib strategy demonstrated comparable or better outcomes than TNFi strategy. Although not powered for safety, no unexpected safety signals were seen in this relatively small group of patients.
CONCLUSION
Up to present, in a T2T setting, patients with RA failing csDMARDs have two main strategies to consider, Janus Kinases inhibitor versus bDMARDs (in clinical practice, predominantly TNFi). The PERFECTRA study suggested that starting with baricitinib was superior over TNFi in achieving response at 12 weeks and resulted in improved outcomes across all studied clinical measures and PROMs throughout the study duration in these patients.
Topics: Humans; Purines; Sulfonamides; Arthritis, Rheumatoid; Pyrazoles; Azetidines; Male; Female; Middle Aged; Antirheumatic Agents; Aged; Treatment Outcome; Tumor Necrosis Factor Inhibitors; Treatment Failure; Adult; Patient Reported Outcome Measures; Severity of Illness Index
PubMed: 38816210
DOI: 10.1136/rmdopen-2024-004291 -
Anais Da Academia Brasileira de Ciencias 2024The epidemiology of psoriasis and cutaneous mycoses is scarce in Brazil. Thus, this cross-sectional study aimed to characterize the distribution of these diseases in...
The epidemiology of psoriasis and cutaneous mycoses is scarce in Brazil. Thus, this cross-sectional study aimed to characterize the distribution of these diseases in Paraná. Data was obtained from the Outpatient Information System (SIA - Sistema de Informações Ambulatoriais), between 2016 and 2020. The procedures were filtered by the International Classification of Diseases (ICD). A total of 201,161 outpatient procedures were registered for psoriasis and psoriatic arthritis. The distribution concerning gender was similar (50.93% feminine; 49.07% masculine). The mean age was 51.55 years. The most frequent procedure was methotrexate dispensing (23.17%), followed by acitretin (14.29%) and adalimumab (12.55%). Adjusting to total population, the prevalence of procedures was 0.35%. Regarding cutaneous mycoses, 1,756 procedures were registered. 65% of them referred to females. White race/color was predominant (82.97%). The mean age was 37.6 years. The distribution concerning age varied according to the type of mycosis. Medical appointments (48.92%) and surgical pathology exam/biopsy (38.71%) were the most frequent procedures. The prevalence of procedures was 0.004%. This is the first epidemiological study using SIA about the population affected by psoriasis, psoriatic arthritis, and cutaneous mycoses in a Brazilian state. We believe that these findings allow relevant contribution to science and public policies in Brazil.
Topics: Humans; Brazil; Male; Female; Psoriasis; Cross-Sectional Studies; Middle Aged; Prevalence; Adult; Dermatomycoses; Young Adult; Adolescent; Aged; Sex Distribution; Age Distribution; Child
PubMed: 38808876
DOI: 10.1590/0001-3765202420230828