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Objectives: Our objective was to assess the efficacy of golimumab (GLM) in patients with poor prognostic factors (PPFs). Methods: This is a post hoc analysis of GO-FORTH Phase 2/3 study. Cluster analysis was used to determine a patient population with high-risk patterns based on seven PPFs suggested by the European Alliance of Associations for Rheumatology recommendations and limited physical function. Radiographic progression, disease activity, and physical function and associated factors were evaluated over 52 weeks. Results: Overall, 261 rheumatoid arthritis patients were classified into three clusters characterised by high disease activity, high C-reactive protein levels, and limited physical function at baseline. GLM showed suppression of progressive modified total sharp score and decreases in Disease Activity Score 28-joint counts with erythrocyte sedimentation rate and Health Assessment Questionnaire – Disease Index, in all the clusters. In Cluster C that showed almost all the PPF characteristics, a higher rate of change in modified total sharp score ≤0 was observed in GLM 100 mg group than in GLM 50 mg group (63.9% versus 46.5%). C-reactive protein concentration and physical limitation were associated with radiographic progression of Cluster C in GLM treatment. Conclusions: GLM was effective in rheumatoid arthritis patients in a subpopulation at high risk of PPF in GO-FORTH study. A dose of 100 mg may be more beneficial in preventing radiographic progression in this population. [ABSTRACT FROM AUTHOR]

Recent studies have reported the occurrence of upper gastrointestinal (UGI) inflammation in patients with ulcerative colitis (UC). However, whether UC-associated UGI and colorectal lesions share pathogenic cytokine profiles and responses to biologics remains unknown. Herein, we report a case of concurrent UC and ulcerative duodenitis (UD) that displayed unique responses to biologic treatment. Although treatment with prednisolone (PSL) failed to induce remission in both disorders, golimumab (GLM) and ustekinumab (UST) were effective against UD and UC, respectively, and remission of both disorders was achieved using UST. Immunofluorescence analyses revealed that numbers of immune cells expressing TNF-α were comparable in both duodenal and rectal mucosa before the treatment. GLM or UST treatment markedly decreased numbers of TNF-α-expressing duodenal immune cells, suggesting the presence of correlation between TNF-α expression and disease activity of UD. In contrast, TNF-α expression was not parallel to disease activity of UC because GLM or PSL failed to induce remission despite a marked reduction in TNF-α expression. Responsiveness to GLM or UST together with immunofluorescence studies suggests that TNF-α and IL-12/23p40 are pathogenic cytokines causing UD and UC, respectively, in the present case. [ABSTRACT FROM AUTHOR]

Introduction: Rheumatoid arthritis (RA) patients can be divided according to the age of disease onset and classified as late‐onset RA ≥ 60 years old or early‐onset RA < 60 years old. Current treatment guidelines do not stipulate any preference regarding the biologic that should be used first in the late‐onset group. This study aims to compare the drug survival times on first biological treatment between late and early‐onset RA patients. Methods: This is a population based cohort study using the medical records of Leumit healthcare services. We included all eligible RA patients between 2000 and 2017. RA patients were divided into late‐ and early‐onset RA groups and compared according to drug survival time on the first biological therapy. Results: The final cohort included 3814 RA patients, 2807 (73.6%) of whom had early‐onset RA. Overall, biologic disease‐modifying anti‐rheumatic drugs (bDMARDs) were used more often among early‐onset compared to late‐onset patients (16.9% vs. 7.8%, p < 0.001). Among early‐onset patients, etanercept was associated with the longest drug survival time on the first biologic, and adalimumab and infliximab were associated with the longest drug survival times among late‐onset patients. No differences were observed in drug survival times between late and early‐onset patients on the first bDMARD, except for abatacept and golimumab with longer drug survival time among early‐onset patients. Conclusion: Late‐onset RA patients were treated with biologics to a lesser extent than early‐onset patients, but no differences were observed in drug survival times at the first bDMARD between the two groups. [ABSTRACT FROM AUTHOR]

PurposeMethodsResultsConclusionTo demonstrate the efficacy and safety of intravenous golimumab infusion in treating juvenile idiopathic arthritis-associated anterior uveitis.This study was a retrospective observation case series. Electronic records of patients diagnosed with juvenile idiopathic arthritis-associated anterior uveitis who received intravenous golimumab infusion were examined.A total of 24 eyes of 13 patients were included in this study. During 12 months before starting intravenous golimumab, the median grade of anterior chamber reaction was 1 (range: 0.5–3), and the median number of flare-ups was 1 (1–3). During 12 months following the start of intravenous golimumab, the median grade of anterior chamber reaction was 0 (range: 0–1), and the median number of flare-ups was 0 (range: 0–1). Before starting intravenous golimumab, the average number of immunomodulatory agents was 2.6 ± 1.0 with a range of 2 to 5. The average age of patients at the time of starting intravenous golimumab was 13.69 ± 5.23 years (range between 5 and 22). A total of 11 (84.6%) patients responded to intravenous golimumab. The medication was discontinued in one patient due to ineffectiveness and in another patient due to the development of psoriasis as an adverse effect. Cystoid macular edema was present in six eyes of three patients which resolved in all six eyes after starting intravenous golimumab.Intravenous golimumab proves to be efficacious and safe for inducing and sustaining remission in JIA and JIA-associated uveitis. Nonetheless, further robust studies with larger sample sizes are needed to substantiate our findings. [ABSTRACT FROM AUTHOR]

Data on the use of golimumab (GLM) during pregnancy are limited. This study evaluated pregnancy outcomes in women treated with GLM during pregnancy. Cumulative data on GLM‐exposed pregnancies from the Company's global safety database (GSD) are summarized. Cases were medically confirmed maternal exposures to GLM during pregnancy or within 3 months prior to conception with a reported pregnancy outcome. Pregnancy outcomes (e.g., live births) and congenital anomalies in prospectively reported cases (i.e., pregnancy outcome not known when first reported to the company) are presented in a descriptive manner. As of May 31, 2022, 261 prospectively reported pregnancies exposed to GLM were reported in the GSD: 214 (82.0%) live births (including six sets of twins), 31 (11.9%) spontaneous abortions (including one set of twins), 13 (5.0%) induced/elective abortions, 2 (0.8%) reported intrauterine death/still birth, and 1 (0.4%) fetal adverse event in an ongoing pregnancy. The majority of pregnancies had exposure to GLM at least in the first trimester of pregnancy. In total, seven congenital anomalies (7/261; 2.7%) were reported. Of these seven congenital anomalies, five were considered major according to EUROCAT classification version 1.4. Among the five prospectively reported congenital anomalies noted in live births (5/214; 2.3%), four were classified as major (4/214; 1.8%). The rates of adverse pregnancy outcomes and major congenital anomalies in prospectively reported pregnancy cases with exposure to GLM in the Company's GSD were consistent with published background rates for the general population. [ABSTRACT FROM AUTHOR]

Purpose: To present the main findings of a post‐authorization safety study assessing pregnancy and infant outcomes after prenatal golimumab exposure in a real‐world setting. Methods: This observational population‐based cohort study included data from pregnancies ending in 2006–2018 (Finland) or 2019 (Denmark, Sweden). Infants born to women with rheumatic diseases or ulcerative colitis diagnoses were identified. Based on prescription fills from 90 days prior to pregnancy until delivery, infants were assigned to one of the four drug‐exposure cohorts: golimumab, other anti‐TNF biologics, other biologics, and nonbiologic systemic therapy, and the general population. Prevalence of adverse pregnancy outcomes, mortality, diagnoses of major congenital anomalies (MCA), and inpatient infections in the infants' first year of life were assessed. Odds ratios and 95% CIs were calculated for MCA and infection. Results: Among 134 infants in the golimumab cohort, none were stillborn or died in the first year of life. MCA were diagnosed in 4.5% of the infants in the golimumab cohort, versus 6.8%, 10.9%, 5.5%, and 4.6% in the other anti‐TNF biologics, other biologics, nonbiologic systemic therapy and general population cohorts, respectively. Inpatient infections were diagnosed in 11% of golimumab‐exposed infants, compared with 9%–11% of infants in the other cohorts. Unadjusted and selected adjusted comparisons showed no association between prenatal golimumab exposure and MCA or infection compared with the other exposure cohorts or general population. Conclusions: The number of infants with prenatal golimumab exposure was low, but results are reassuringly consistent with the evidence available for other anti‐TNF biologics. Continued monitoring is needed. [ABSTRACT FROM AUTHOR]

Background: The Juan-Bi decoction (JBD) is a classic traditional Chinese medicines (TCMs) prescription for the treatment of rheumatoid arthritis (RA). However, the active compounds of the JBD in RA treatment remain unclear. Aim: The aim of this study is to screen effective compounds in the JBD for RA treatment using systems pharmacology and experimental approaches. Method: Botanical drugs and compounds in the JBD were acquired from multiple public TCM databases. All compounds were initially screened using absorption, distribution, metabolism, excretion, and toxicity (ADMET) and physicochemical properties, and then a target prediction was performed. RA pathological genes were acquired from the DisGeNet database. Potential active compounds were screened by constructing a compound-target-pathogenic gene (C-T-P) network and calculating the cumulative interaction intensity of the compounds on pathogenic genes. The effectiveness of the compounds was verified using lipopolysaccharide (LPS)-induced RAW.264.7 cells and collageninduced arthritis (CIA) mouse models. Results: We screened 15 potentially active compounds in the JBD for RA treatment. These compounds primarily act on multiple metabolic pathways, immune pathways, and signaling transduction pathways. Furthermore, in vivo and in vitro experiments showed that bornyl acetate (BAC) alleviated joint damage, and inflammatory cells infiltrated and facilitated a smooth cartilage surface via the suppression of the steroid hormone biosynthesis. Conclusion: We screened potential compounds in the JBD for the treatment of RA using systems pharmacology approaches. In particular, BAC had an anti-rheumatic effect, and future studies are required to elucidate the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Treatment for pregnant women with psoriasis is limited by the lack of information typically related to clinical trials. While anti-tumor necrosis factor (TNF) drugs offer therapeutic benefits, their safety during pregnancy is a concern. Notably, certolizumab is comparatively safer than adalimumab, etanercept, infliximab, and golimumab according to the current recommendations. Thus, this study aimed to conduct a pharmacovigilance comparative analysis of maternal and neonatal outcomes associated with certolizumab versus other anti-TNF drugs by using data from EudraVigilance. A descriptive analysis was performed of Individual Case Safety Reports (ICSRs) associated with an anti-TNF drug and related to the pregnant patients with psoriasis from 2009 and 2023, focusing our analysis on the specific pregnancy outcomes and fetal/neonatal disorders. The most common pregnancy-related adverse event was spontaneous abortion, predominantly related to adalimumab and certolizumab. Certolizumab was also reported in cases of caesarean section, gestational diabetes, abortion, fetal death, fetal distress syndrome, pre-eclampsia, and premature separation of placenta. Generally, the findings from our study depicted a safety profile that overlapped for each anti-TNF drug, both in maternal/neonatal outcomes and other adverse events, suggesting no substantial differences between treatments. We advocate for further investigations before making concrete recommendations. [ABSTRACT FROM AUTHOR]

Background/Objectives: To date, the literature concerning real-world data on the retention rate and safety of Janus kinase inhibitors (JAKis) is limited. To retrospectively evaluate the overall drug retention rate (DRR) of different JAKis in a monocentric cohort of patients with rheumatoid arthritis (RA). Methods: Patients diagnosed with RA and treated with JAKis who were evaluated at our outpatient clinic from March 2017 to December 2023 were included in the study. Demographic, clinical characteristics, and comorbidities were recorded. The DRR was evaluated as the time to drug discontinuation, and baseline predictors of drug discontinuation were investigated through Cox regression after adjusting for baseline confounders. Results: The global DRR for JAKis was 51.3%. The DRR was 37.5% for tofacitinib, 46.6% for baricitinib, 69.4% for upadacitinib, and 53.5% for filgotinib. Considering all JAKis, the only significant predictor of drug discontinuation was the use of JAKis as a first-line treatment (HR 95% CI [0.25 (0.13–0.46)]. When considering each JAKi individually, a longer disease duration predicted TOF discontinuation (HR95% CI [1.05 (1.01–1.09)], while seropositivity protected against TOF being withdrawn (HR95% CI [0.41 (0.17–0.97)]. No independent predictors emerged for other JAKis. Conclusions: the use of JAKis as a first-line treatment as well as disease duration and serology may impact the DRR of JAKis, which may inform tailored treatment strategies in clinical practice. [ABSTRACT FROM AUTHOR]

For psoriatic patients who need to receive nonlive or live vaccines, evidence-based recommendations are needed regarding whether to pause or continue systemic therapies for psoriasis and/or psoriatic arthritis. To evaluate literature regarding vaccine efficacy and safety and to generate consensus-based recommendations for adults receiving systemic therapies for psoriasis and/or psoriatic arthritis receiving nonlive or live vaccines. Using a modified Delphi process, 22 consensus statements were developed by the National Psoriasis Foundation Medical Board and COVID-19 Task Force, and infectious disease experts. Key recommendations include continuing most oral and biologic therapies without modification for patients receiving nonlive vaccines; consider interruption of methotrexate for nonlive vaccines. For patients receiving live vaccines, discontinue most oral and biologic medications before and after administration of live vaccine. Specific recommendations include discontinuing most biologic therapies, except for abatacept, for 2-3 half-lives before live vaccine administration and deferring next dose 2-4 weeks after live vaccination. Studies regarding infection rates after vaccination are lacking. Interruption of antipsoriatic oral and biologic therapies is generally not necessary for patients receiving nonlive vaccines. Temporary interruption of oral and biologic therapies before and after administration of live vaccines is recommended in most cases. [ABSTRACT FROM AUTHOR]

Background: Disease-modifying anti-rheumatic drugs (DMARDs), since their introduction in 1990, have revolutionized the management of rheumatoid arthritis. Newer DMARDs have recently been approved, influencing treatment patterns and clinical guidelines. Objective: To update the current prescribing patterns of DMARDs in the pharmacotherapy of rheumatoid arthritis (RA) to include the pandemic era. Methods: This was a retrospective cross-sectional multi-year study. Using Optum's Clinformatics® Data Mart Database, we summarized trends in the prevalence of DMARD use in the USA from 2016 to 2021 by year for adult patients ≥ 18 years old with at least one medical RA claim and one pharmacy/medical claim of a DMARD medication. Trends included type of DMARD, class of DMARD (conventional (csDMARDs), biologics [tumor necrosis factor (TNFi) and Non-TNFi), and Janus kinase inhibitors (JAKs)], and triple therapy [methotrexate (MTX), hydroxychloroquine (HCQ), sulfasalazine (SUL)] used. Results: The total sample from 2016 to 2021 was 670,679 commercially insured patients. The average age was 63.7 years (SD 13.6), and 76.7% were female and 70% were White. csDMARDs remain the most prescribed (ranging from 77.2 to 79.2%). Although JAKs were the least prescribed DMARD class, their proportion more than doubled from 2016 (1.5%) to 2021 (4%). MTX utilization declined from 40% in 2016 to 34% in 2021. In contrast, HCQ use increased during the pandemic era from < 25% in 2018 to 30% in 2021. Although there is evidence of the therapeutic benefit of triple therapy, its use was very low (~ 1%) compared to biologics only (~ 17%) or biologics+MTX (~ 10%). Conclusion: About half of patients with RA were on DMARDs. As expected, csDMARDs were highly used consistently. The COVID-19 pandemic might have influenced the use of HCQ and infusion DMARDs. Triple therapy use remains low. [ABSTRACT FROM AUTHOR]

A proof‐of‐concept study with the combination of guselkumab and golimumab in patients with ulcerative colitis (UC) has shown that the combination therapy resulted in greater efficacy than the individual monotherapies. The current analysis evaluated the pharmacokinetics (PK) and immunogenicity of guselkumab and golimumab in both the combination therapy and individual monotherapies. Blood samples were collected to evaluate serum concentrations and immunogenicity of guselkumab and golimumab. Population PK (PopPK) models were developed to assess the effects of combination therapy and other potential covariates on the PK of guselkumab and golimumab. The guselkumab PK was comparable between monotherapy and combination therapy, whereas golimumab concentrations were slightly higher with combination therapy. The anti‐guselkumab antibody incidence was low with both monotherapy and combination therapy, and guselkumab immunogenicity did not impact the clearance. Conversely, the anti‐golimumab antibody incidence with combination therapy was lower than that for monotherapy. PopPK analysis suggested that the slightly higher golimumab concentrations with combination therapy were partially due to lower immunogenicity and thus lower clearance with combination therapy. C‐reactive protein (CRP) was also a significant covariate on golimumab clearance. The greater improvement of inflammation with combination therapy, as shown by reductions in CRP, may have also contributed to the higher golimumab concentrations. Combination therapy slightly decreased the clearance of golimumab, but not guselkumab clearance, in patients with UC. Lower immunogenicity and greater improvement of inflammation with combination therapy were potential mechanisms for slightly increased golimumab concentrations with combination therapy as compared with golimumab monotherapy. [ABSTRACT FROM AUTHOR]

Hemophagocytic lymphohistiocytosis (HLH) secondary to Histoplasma capsulatum is rare, impacting <1% globally, with a mortality rate of up to 31%. Herein, we present a rare case of HLH secondary to H capsulatum, affecting a 57-year-old female with rheumatoid arthritis. Extensive investigations were unrevealing and despite broad-spectrum antibiotics, her condition worsened, leading to respiratory failure requiring extracorporeal membrane oxygenation (ECMO) support, shock requiring multiple vasopressors, and acute kidney injury (AKI) requiring hemodialysis. Diagnosis confirmed disseminated histoplasmosis (DHP), prompting Amphotericin B and methylprednisolone treatment, resulting in significant improvement and discharge with posaconazole therapy. Secondary HLH, primarily arising from severe infections like DHP, is discussed. Limited research exists on this condition in human immunodeficiency virus (HIV)-seronegative individuals. Diagnosis involves HLH-2004 and HScore criteria. Managing histoplasmosis-associated HLH remains challenging due to multiorgan failure risks and treatment complexities and needs further research. [ABSTRACT FROM AUTHOR]

Acne inversa is a chronic, progressive inflammatory skin disease. It is characterized by the occurrence of relapsing, painful, deep-seated nodules, abscesses, fistulae, sinus tracts, and scars in the axilla, inguinal area, submammary folds, and perianal area. The disease significantly affects patients’ quality of life and is often associated with severe, debilitating pain and depression. Pro-inflammatory cytokines such as TNF-α, interleukin 17 (IL-17), IL-23, IL-12, IL-1α, and IL-1β play a significant role in the pathogenesis of hidradenitis suppurativa. Treatment is difficult and often ineffective, based on both surgical and pharmacological methods. Biologic drugs in hidradenitis suppurativa are the subject of many clinical trials and may be effective in patients for whom other therapies have failed. The first biological drug approved by the Food and Drug Administration for the treatment of hidradenitis suppurativa was the TNF-α inhibitor — adalimumab. The advancement of knowledge of immune mechanisms in the pathogenesis of hidradenitis suppurativa has allowed the development of clinical trials of new therapeutic targets. In 2023, the Food and Drug Administration (FDA) approved the IL-17 inhibitor — secukinumab as the second biological drug in hidradenitis suppurativa. The aim of this review is an update of the biological treatment and its effectiveness in hidradenitis suppurativa. [ABSTRACT FROM AUTHOR]

Background: The early identification of patients' profiles most likely to respond to and maintain long-term therapy with a biological drug can have clinical and cost-effectiveness implications. Objectives: To evaluate the utility of an innovative approach for early identification of patient profiles associated with long-term persistence of golimumab, a tumour necrosis factor inhibitor, in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (SpA) under real-world conditions. Design: Retrospective non-interventional database analysis. Methods: Kaplan-Meier curves of golimumab retention over 8 years from the BIOBADASER registry, overall and by indication, were analysed using a novel approach (a two-phase decay model) to identify the point at which the golimumab retention curve shifted from rapid (indicating high golimumab discontinuation rate) to slow decay (low discontinuation rate). Factors associated with golimumab retention at these time points were identified using Cox regression, and retention rates for different patient profiles were calculated. Results: 885 patients were included. The golimumab retention curve shifted from rapid to slow decay at month 10 for the overall population (retention rate: 73.4%), at month 24 for RA patients (retention: 45.0%), and at month 8 for SpA, including axial SpA and PsA (81.6%). Factors associated with golimumab discontinuation at these early points were, overall, similar to those previously identified at year 8 (RA diagnosis, golimumab as second- or third-line of biological therapy, disease activity over the median and treatment with corticosteroids at golimumab initiation, advanced age [in RA], and female gender [in SpA]). Conclusion: With this novel approach, the factors associated with long-term retention were identified in the initial period of rapid discontinuation of golimumab. [ABSTRACT FROM AUTHOR]

The article discusses the effectiveness and persistence of golimumab (GLM) as a second-line treatment for rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) in Italy. The study found that after 12 months of GLM treatment, a significant number of patients achieved low disease activity or minimal disease activity. The overall persistence rate at 12 months was high, indicating that GLM had a favorable benefit-risk profile and was well-tolerated by patients. The study also found improvements in disease activity measures and quality of life scores. These findings support the use of GLM as a second-line treatment option for these conditions. [Extracted from the article]

Abstract Data on the use of golimumab (GLM) during pregnancy are limited. This study evaluated pregnancy outcomes in women treated with GLM during pregnancy. Cumulative data on GLM‐exposed pregnancies from the Company's global safety database (GSD) are summarized. Cases were medically confirmed maternal exposures to GLM during pregnancy or within 3 months prior to conception with a reported pregnancy outcome. Pregnancy outcomes (e.g., live births) and congenital anomalies in prospectively reported cases (i.e., pregnancy outcome not known when first reported to the company) are presented in a descriptive manner. As of May 31, 2022, 261 prospectively reported pregnancies exposed to GLM were reported in the GSD: 214 (82.0%) live births (including six sets of twins), 31 (11.9%) spontaneous abortions (including one set of twins), 13 (5.0%) induced/elective abortions, 2 (0.8%) reported intrauterine death/still birth, and 1 (0.4%) fetal adverse event in an ongoing pregnancy. The majority of pregnancies had exposure to GLM at least in the first trimester of pregnancy. In total, seven congenital anomalies (7/261; 2.7%) were reported. Of these seven congenital anomalies, five were considered major according to EUROCAT classification version 1.4. Among the five prospectively reported congenital anomalies noted in live births (5/214; 2.3%), four were classified as major (4/214; 1.8%). The rates of adverse pregnancy outcomes and major congenital anomalies in prospectively reported pregnancy cases with exposure to GLM in the Company's GSD were consistent with published background rates for the general population.