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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 Jul 2024To analyze the long-term survival of subcutaneous biosimilar tumor necrosis factor inhibitors compared to the originator molecules in patients with rheumatic diseases,...
OBJECTIVE
To analyze the long-term survival of subcutaneous biosimilar tumor necrosis factor inhibitors compared to the originator molecules in patients with rheumatic diseases, as well as the factors associated with drug discontinuation.
METHODS
Retrospective analysis of BIOBADASER, the Spanish multicenter prospective registry of patients with rheumatic disease receiving biologic and targeted disease-modifying antirheumatic drugs. Patients who started etanercept (ETN) or adalimumab (ADA) 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 causes (inefficacy or adverse events [AEs]) of discontinuation.
RESULTS
A total of 4162 patients received 4723 treatment courses (2991 courses of ADA and 1732 courses of ETN), of which 722 (15.29%) were with originator molecules and 4001 (84.71%) were with biosimilars. The originators were more frequently discontinued than biosimilars (53.32% vs 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, whereas disease duration and the use of concomitant methotrexate were associated with 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 treatments in long-term survival due to inefficacy or AEs.
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 -
Cureus Apr 2024In a rural Japanese setting, this case report delves into managing a post-partum woman diagnosed with ankylosing spondyloarthritis (AS), showcasing the complexities of...
In a rural Japanese setting, this case report delves into managing a post-partum woman diagnosed with ankylosing spondyloarthritis (AS), showcasing the complexities of balancing effective pain relief with breastfeeding. The study highlights a multifaceted approach that incorporates medical treatment, psychosocial support, and comprehensive patient education, which are essential in rural healthcare where resources may be scarce. Initially managed with diclofenac due to its safer profile for breastfeeding, the patient's treatment was eventually escalated to adalimumab, aligning with improved circumstances regarding breastfeeding. This case emphasizes the critical role of holistic, patient-centered care in family medicine, particularly for managing maternal and child health chronic conditions. It illustrates how integrating mental health support, acknowledging patient fears, and educating families can significantly enhance patient care and outcomes. Through this approach, the report advocates for a broader application of family medicine principles to improve maternal and child health services in rural settings, demonstrating the importance of tailored healthcare strategies that consider patients' medical and emotional needs.
PubMed: 38807812
DOI: 10.7759/cureus.59187 -
RMD Open May 2024To assess the safety and efficacy of upadacitinib versus adalimumab from SELECT-COMPARE over 5 years. (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
OBJECTIVES
To assess the safety and efficacy of upadacitinib versus adalimumab from SELECT-COMPARE over 5 years.
METHODS
Patients with rheumatoid arthritis and inadequate response to methotrexate were randomised to receive upadacitinib 15 mg once daily, placebo or adalimumab 40 mg every other week, all with concomitant methotrexate. By week 26, patients with insufficient response to randomised treatment were rescued; patients remaining on placebo switched to upadacitinib. Patients completing the 48-week double-blind period could enter a long-term extension. Safety and efficacy were assessed through week 264, with radiographic progression analysed through week 192. Safety was assessed by treatment-emergent adverse events (TEAEs). Efficacy was analysed by randomised group (non-responder imputation (NRI)) or treatment sequence (as observed).
RESULTS
Rates of TEAEs were generally similar with upadacitinib versus adalimumab, although numerically higher rates of herpes zoster, lymphopenia, creatine phosphokinase elevation, hepatic disorder and non-melanoma skin cancer were reported with upadacitinib. Numerically greater proportions of patients randomised to upadacitinib versus adalimumab achieved clinical responses (NRI); Clinical Disease Activity Index remission (≤2.8) and Disease Activity Score based on C reactive protein <2.6 were achieved by 24.6% vs 18.7% (nominal p=0.042) and 31.8% vs 23.2% (nominal p=0.006), respectively. Radiographic progression was numerically lower with continuous upadacitinib versus adalimumab at week 192.
CONCLUSION
The safety profile of upadacitinib through 5 years was consistent with the known safety profile of upadacitinib, with no new safety risks. Clinical responses were numerically higher with upadacitinib versus adalimumab at 5 years. Upadacitinib demonstrates a favourable benefit-risk profile for long-term rheumatoid arthritis treatment.
TRIAL REGISTRATION NUMBER
NCT02629159.
Topics: Humans; Arthritis, Rheumatoid; Adalimumab; Heterocyclic Compounds, 3-Ring; Female; Antirheumatic Agents; Male; Middle Aged; Treatment Outcome; Double-Blind Method; Adult; Methotrexate; Aged; Drug Therapy, Combination
PubMed: 38806190
DOI: 10.1136/rmdopen-2023-004007 -
American Journal of Clinical Dermatology Jul 2024
Topics: Humans; Psoriasis; Ustekinumab; Interleukin-23; Treatment Outcome; Female; Male; Dermatologic Agents; Middle Aged; Drug Substitution; Antibodies, Monoclonal, Humanized; Adult; Severity of Illness Index; Retrospective Studies; Adalimumab
PubMed: 38802618
DOI: 10.1007/s40257-024-00868-x