bDMARD Treatment Research Articles

The pattern of anti-IL-6 versus non-anti-IL-6 biologic disease modifying anti-rheumatic drugs use in patients with rheumatoid arthritis in Wales, UK: a real-world study using electronic health records.

Investigating factors associated with drug initiation and discontinuation in patients treated with anti-IL-6 biologic DMARDs (bDMARDs) (tocilizumab or sarilumab) vs non-anti-IL-6 (anti-TNF, B or T cell therapies) bDMARDs for RA. A retrospective cohort study of patients with the diagnosis of RA in the Secure Anonymised Information Linkage Databank, comprising primary and secondary care and specialist rheumatology clinic records for >90% of the population in Wales, UK. Patients initiated on first bDMARD treatment, discontinuation and clinical outcomes including infection and hospitalisation were analysed using Cox regression analysis. Of patients identified with RA in their primary care records, 95.7% (4691/4922) received conventional synthetic DMARDs (csDMARDs). More than one-third (36.2%) were treated with bDMARDs (1784/4922). Of these biologic-naïve patients, 6.5% (116) were treated with anti-IL-6 bDMARDs; this treatment was associated with a previous history of infection [difference 8.8% (95% CI 1.1, 17.8)] and kidney disease [14.3% (95% CI 8.0, 22.5)]. Treatment discontinuation was significantly higher in the non-anti-IL-6 bDMARD-treated patients (23.1%) compared with the anti-IL-6 bDMARD-treated individuals (18.1%) [difference 9.4% (95% CI 1.1, 15.7)]. For those discontinuing a first line of treatment, 385 patients (23%) and 21 patients (18%) switched to an alternative bDMARD from the non-anti-IL-6 and anti-IL-6 groups, respectively. Comorbidities, history of infection and kidney disease were associated with choosing anti-IL-6 bDMARDs in biologic-naïve RA patients in Wales. Anti-IL-6 bDMARD-treated biologic-naïve patients were more likely to continue treatment than non-IL-6 bDMARD-treated patients.

25 Years of Biologics For The Treatment of Pediatric Rheumatic Diseases - Advances in Prognosis and Ongoing Challenges.

There are over 100 rheumatic diseases and approximately 300,000 children with a pediatric rheumatic disease (PRD) in the United States (U.S.). The most common PRDs are juvenile idiopathic arthritis (JIA), childhood-onset systemic lupus erythematosus (cSLE), and juvenile dermatomyositis (JDM). Effective and safe medications are essential because there are generally no cures for these conditions. Etanercept was the first biologic therapy for the treatment of JIA, approved in 1999. Since then, other biologic disease modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARD (tsDMARDs) blocking relevant immunological pathways have been approved for the treatment of JIA, resulting in a marked improvement of disease prognosis. Conversely, there is only one bDMARD that has been approved for cSLE, but none are approved for the treatment of JDM. Lack of approved therapeutic options, with established dosing regimens and known efficacy and safety, remains a central challenge in the treatment of all PRDs, including autoinflammatory diseases, and for complications of PRDs. This review provides an overview of bDMARD and tsDMARD treatments studied for the treatment of various subtypes of JIA, summarizes information from bDMARD studies in other pediatric rheumatic diseases, with a focus on pivotal trials that led to regulatory approvals and highlights improved outcomes in JIA with the use of these newer medications. Further, we outline barriers and challenges in the treatment of other PRDs. Lastly, we summarize the current regulatory landscape for bDMARD studies and medication approvals in PRDs.

Preferences for Tapering Biologic Disease-Modifying Antirheumatic Drugs Among People With Rheumatoid Arthritis: A Discrete Choice Experiment.

Little is known about the preferences of people with rheumatoid arthritis (RA) regarding tapering of biologic disease-modifying antirheumatic drugs (bDMARDs). The aim of this study was to assess the preferences of people with RA in relation to potential treatment-related benefits and risks of bDMARD tapering and the health care service-related attributes that affect tapering. Participants with RA who had experience taking a bDMARD completed an online discrete choice experiment. Participants were asked their preferences when given three hypothetical treatment scenarios in which varying the frequency of treatment might alter their chance of adverse effects, of regaining disease control, and of other health care service-related effects. Preference weights were estimated using a multinomial logit model. There were 142 complete responses. Reduced dosing frequency of bDMARD treatment had the largest impact on preference (mean 1.0, 95% confidence interval [CI] 0.8-1.2), followed by chance of disease flare (mean 0.7, 95% CI 0.6-0.9). Participants were willing to accept an increased risk of flare between 10.6% (95% CI 3.2-17.9) and 60.6% (95% CI 48.1-72.9) in exchange for benefits associated with tapering bDMARDs. Participants with better quality of life were more likely to choose to remain on current treatment. The predicted uptake of bDMARD tapering was high among people with RA, suggesting bDMARD tapering was a favored option. For individuals with RA, making decisions about tapering bDMARDs involves considering several factors, with the most important determinants identified as dosing frequency and the risk of disease flare. Understanding patient perspectives of bDMARD tapering may enable physicians to make patient-focused shared health care decisions.

A retrospective study of efficacy of tofacitinib combined with bDMARDs in the treatment of rheumatoid arthritis patients with inadequate response to bDMARDs.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovial inflammation, joint swelling, and pain involving multiple joints. While biologic disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) are popular treatments for RA, there is limited research on their combined use. This study examined a cohort of RA patients who demonstrated inadequate response to bDMARDs and subsequently initiated combination therapy with tofacitinib and bDMARDs, assessing both the efficacy and safety profile of this therapeutic approach. In this study, we retrospectively collected the electronic medical records (EMR) of 62 adult patients with RA who were admitted to the Fourth Affiliated Hospital Zhejiang University School of Medicine between August 2018 and December 2022. All patients had received at least one bDMARD treatment for more than 3 months and still exhibited moderate-to-high disease activity. Tofacitinib 5 mg bid was added to their original biological treatment in 28 cases, and other 34 cases switched to another bDMARD or tsDMARD as control group. Treatment was continued for 24 weeks following the initiation of combination therapy. Changes in DAS28-ESR and ACR20, 50, 70 response rates at week 24 were collected and analyzed from baseline, while changes in C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) at weeks 4, 8, 12, 24 were also collected and analyzed. After 24 weeks of treatment, the DAS28-ESR score in combined treatment group decreased significantly from a baseline of 5.26 ± 0.90 (3.87-8.31) to 2.67 ± 0.86 (1.41-5.11), with remission achieved by 19 patients (67.9%) and low disease activity achieved by five patients (17.9%). The DAS28-ESR in the control group exhibited a decrease from 5.20 ± 0.77 (3.87-7.23) at baseline to 3.25 ± 1.29 (1.54-5.69). In all, 13 patients (38.2%) achieved remission, while another 11 patients (32.4%) achieved low disease activity. The ACR20, 50, 70 response rates were 85.71%, 75%, and 39.29% in the combined treatment group, whereas it were 75.0%, 53.57%, 21.43% in the control group. Additionally, both ESR and CRP levels decreased significantly during the course of treatment without any reported adverse events leading to discontinuation. Our findings offer some evidence, supporting the effectiveness and safety of combining bDMARD with JAKi tofacitinib in RA patients who have an inadequate response to bDMARD monotherapy. This combination effectively manages disease activity while maintaining a relatively low and manageable incidence of adverse events. Further prospective randomized controlled trials with large sample sizes are anticipated to provide evidence-based medical support.

Predictors of Drug Retention and Survival Rate of bDMARDs in Rheumatoid Arthritis: A Four-Year Real-Life Tunisian Experience.

This study aims to investigate the efficacy and tolerance of biologic disease-modifying anti-rheumatic drug (bDMARDs) in the current management of rheumatoid arthritis (RA) by identifying the retention time and survival rate of bDMARDs. We conducted a retrospective cohort study including Tunisian patients initiating bDMARD treatment between 2016 and 2018 whose data were collected from the National Health Insurance Fund (NHIF). The NHIF is the national office which organises and centralises patients under bDMARDs from all over the country. Retention and survival rate of bDMARDs at 48 months were analysed using Kaplan-Meier survival curves and compared using the log-rank test. Survival factor analysis was performed using Cox regression. Three hundred seventy-four patients, aged 55.5±12.5years [20-90], (87.2%women), were included. The mean duration of RA was 11.7±6.7 years [2-41]. The mean disease activity score (DAS)28 at initiation of the first bDMARD was 6.01±0.89 [5.37-6.5]. This first bDMARD induced low disease activity (LDA) in 55% of cases. Remission was observed in 28% of patients. The highest LDA and remission rates were observed with Tocilizumab (70.8% and 33.3% of cases, respectively). LDA and remission were achieved within a mean of 45 weeks [26-88] and 72 weeks [31-117] respectively. The 48-month first-line survival rate was 55.9%. Retention time was 41.7 months, 95%CI [39.47-43.91]. Presence of rheumatoid factors, co-prescription of methotrexate, and good initial therapeutic response were factors influencing better survival of bDMARDs (p<0.01). Glucocorticoid use predicted poorer survival (p<10-3). The first bDMARD was interrupted in 39% of cases. Ineffectiveness was the most common cause of treatment cessation (52.7%). This real-life study of the Tunisian population allowed us to establish the factors that can influence the survival and retention rates of bDMARDs.

Real-world risk factors for herpes zoster in patients with rheumatoid arthritis undergoing tofacitinib treatment.

This study sought to assess the risk factors of herpes zoster (HZ) in rheumatoid arthritis (RA) patients treated with tofacitinib (TOFA). This retrospective study reviewed RA patients receiving TOFA. We compared clinical characteristics, laboratory profiles, concomitant medication use, and HZ incidence in patients with and without recent biologic synthetic disease-modifying antirheumatic drugs (bDMARDs) treatment, which is defined as their administration ≤180 days before the initiation of TOFA treatment. We used univariate Cox proportional hazards models and Kaplan-Meier analysis to assess risk factors. Among 304 RA patients, 97 had recent bDMARDs use and 207 did not. Patients with recent bDMARDs use typically had lower weekly doses of methotrexate, less hydroxychloroquine use, and shorter follow-up. In the recent bDMARDs group, 64 (66.0%) used tumor necrosis factor inhibitors (TNFi), 19 (19.6%) used tocilizumab, and 14 (14.4%) used abatacept. The overall incidence rate (IR) of HZ was 5.62 per 100 person-years. Patients with recent bDMARDs use exhibited a higher HZ risk compared to those without recent bDMARDs use (IR ratio: 2.34, 95% CI, 1.04-5.19, p = 0.028). Recent bDMARDs use (hazard ratio: 2.4, 95% CI, 1.12-4.95, p = 0.024) was an independent risk factor for HZ among multivariable analysis. Kaplan-Meier analysis confirmed increased HZ risk in RA patients on TOFA with recent bDMARDs use (log-rank p = 0.015). HZ is common in RA patients treated with TOFA, and recent bDMARDs (TNFi, tocilizumab, and abatacept) use is a risk factor for HZ. HZ vaccination, therefore, should be recommended for this group.

Head-to-head studies on psoriasis and psoriatic arthritis

Given the ever-increasing number of approved therapies for the treatment of psoriasis (PsO) and psoriatic arthritis (PsA), head-to-head (H2H) comparative studies are essential. These are aimed primarily at acomparative analysis of treatment effectiveness. In both PsO and PsA, biological disease-modifying antirheumatic drugs (bDMARD) have been shown to be superior to conventional therapies in H2H studies. In PsO interleukin 17 (IL-17) and IL-23 inhibitors proved superiority compared to tumor necrosis factor (TNF) inhibitors (etanercept and adalimumab) in several studies. Ustekinumab was more effective than etanercept, but less effective than IL-17 and IL-23 inhibitors. Only afew H2H studies have been published on the treatment of PsA. In the Spirit H2H study ixekizumab was superior to adalimumab using acombined endpoint of arthritis and psoriasis response (ACR-50 and PASI-100). When looking at arthritic symptoms only (ACR-20), secukinumab was not significantly superior to adalimumab in the EXCEED study but was superior in terms of the effect on skin involvement (PASI90). Other H2H studies focused on the treatment of enthesitis (ECLIPSA study), the efficacy of Janus kinase (JAK) inhibition (SELECT-PSA-1) or the additional administration of methotrexate to bDMARD treatment (MUST study). The H2H data have been incorporated into the treatment guidelines and have led to IL-17 and IL-23 inhibition being preferred over TNF inhibition in cases of relevant skin involvement in PsA.

Four-year real-world experience of secukinumab in a large Italian cohort of axial spondyloarthritis.

This study aims to evaluate in a real-life Italian multicenter cohort of axial spondyloarthritis (axSpA) (1) the 4-year effectiveness and safety of secukinumab, (2) the drug retention rate (DRR), and (3) the impact of the line of bDMARDs treatment, subtype of axSpA, and sex on achieving low disease activity (LDA) and very low disease activity (VLDA). Consecutive axSpA patients receiving secukinumab between 2016 and 2023 were prospectively evaluated. Data on disease characteristics, previous/ongoing treatments, comorbidities, and follow-up duration were collected. Treatment response was evaluated at 6 and 12 months after initiation and yearly up to 48 months (T48). DRR and effectiveness outcomes were evaluated according to bDMARDs treatment, axSpA subtype, and sex. Infections and adverse events (AEs) were recorded. We enrolled 272 patients (48.2% male; median age, 51; 39.7% HLA-B27+; 40.4% nr-axSpA), of whom 30.9% were naïve to secukinumab. Overall, secukinumab yielded improvement in effectiveness outcomes; the naïve patients maintained lower disease activity vs. the non-naïve ones. At T48, the LDA and VLDA rates were higher in naïve patients and in male individuals. Treatment was discontinued in 104 patients due to primary/secondary loss of effectiveness and in 34 patients due to AEs. The DRR at T48 was 67.4% in the whole population, regardless of treatment line, axSpA subtype, and sex. Secukinumab was safe and effective in all axSpA patients irrespective of treatment line, disease subtype, and sex. The patients achieved sustained 4-year remission and DRR.

Early clinical response associates with long-term outcomes with ixekizumab in radiographic axial spondyloarthritis

BackgroundThe Assessment of SpondyloArthritis international Society-European Alliance of Associations for Rheumatology recommendations for axial spondyloarthritis (axSpA) management include patient assessment for biological disease-modifying antirheumatic drug (bDMARD) treatment response after at...

Effect of biologic agents and inflammation on lipid levels and cardiovascular risk in rheumatoid arthritis patients

BackgroundCardiovascular disease (CVD) is the main cause of mortality in Rheumatoid Arthritis (RA). ObjectiveTo investigate the effect of biologic disease modifying anti-rheumatic drugs (bDMARDs) on lipids and CVD risk and evaluate associations with changes in systemic inflammation. MethodsPatients with RA initiating a bDMARD were evaluated at baseline, 3 and 6 months later. Longitudinal mixed effects models examined the association of individual biologics with changes in lipid levelsm Reynolds Risk Score (RRS) and Framingham risk score. Mediation by CRP, clinical disease activity index (CDAI) or swollen joint count on lipid changes were modeled using structural equation models. The correlation between CRP changes and LDL changes was estimated. Changes of LDL-C at 6 months among patients with low baseline LDL-C (<90 mg/dl) vs higher baseline LDL-C(90–130, and >130 mg/dl) were compared. The association between LDL-C changes across baseline LDL-C groups and disease activity improvement was evaluated. Results1698 bDMARD initiations were analyzed. Patients initiating tocilizumab had a significant increase in lipid levels but RRS at 3 and 6 months was similar across all biologics. Framingham risk score increased for patients treated with tocilizumab. Mediator analyses were statistically significant for the effects of CRP on lipid levels. Increases in LDL-C from baseline were independent of clinical response. An association of changes from baseline CRP and LDL-C were observed across all of the bDMARDs studied. ConclusionModerate increases in lipid levels on bDMARD treatment were not associated with an increased CVD risk by RRS regardless of the bDMARD initiated. Changes in CRP were significantly associated with changes in lipids in a mediator analysis.

The steroid-sparing effect of JAK inhibitors across multiple patient populations.

JAK-inhibitors (JAK-i) represent an effective treatment in Rheumatoid Arthritis (RA) and Psoriatic Arthritis (PsA). Oral glucocorticoids (OGC) are commonly used in combination with JAK-i to reach therapeutic target. We aimed to assess, in a real-life setting, the reduction of OGC dose during JAK-i treatment in active RA and PsA patients. We prospectively enrolled 103 patients (88 RA, 15 PsA) treated with JAK-i: 24% bio-naïve (b-naïve), 76% bDMARD-insufficient responders (bDMARD-IR) and 40% difficult to treat (D2T), defined as failure of ≥2 bDMARDs with different mechanism of action. Disease activity (DAS28 and DAPSA, VAS-pain, GH) and OGC dose was collected at baseline and after 3, 6 and 12 months (T3, T6, T12) of treatment. In all the cohort and in b-naïve patients we reported a reduction of OGC dose at all time-points; bDMARD-IR patients were able to reduce OGC dose at T3 and T12; D2T ones only at T3. We reported an improvement of disease activity and withdrawal of OGC as early as three months of therapy, at all time-points, regardless of line of bDMARD treatment. Chronic OGC may cause detrimental bone, metabolic, cardiovascular side effects and infections; therefore JAK-i steroid-sparing effect may be beneficial for patients in long-term treatment.

The changes of intestinal flora and its relevance with memory Tfh and B cells in rheumatoid arthritis patients treated with csDMARDs and csDMARDs + bDMARDs

BackgroundA growing body of experimental and clinical evidence has implicated gut microbiota in the onset and course of rheumatoid arthritis (RA). The imbalance of intestinal flora in RA patients may lead to abnormal expression of immune cells and related cytokines. PurposeConventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and conventional synthetic disease-modifying antirheumatic drugs combined with biological disease-modifying antirheumatic drugs (csDMARDs + bDMARDs) are widely used to treat RA, but the characteristics of gut microbiota before and after treatment and their relationship with memory Tfh/B cells and cytokines remain unclear. MethodsStool samples were collected from 50 RA patients and 25 healthy controls (HCs) for 16SrRNA gene sequencing. We examined the proportion of lymphocyte subsets in healthy controls and RA patients. Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of related cytokines in serum. The α and β diversity of intestinal flora, and the correlation between intestinal flora and clinical indicators, lymphocyte subsets, cytokines were analyzed. ResultAt the genus level, Ruminococcaceae_Ruminococcus was decreased in the csDMARDs and csDMARDs + bDMARDs treatment group, whereas Faecalibacterium was reduced in the csDMARDs treatment group, compared to untreated group. CD4+CD45RO+CCR7+CXCR5+central memory Tfh cells and CD4+CD45RO+CCR7-CXCR5+effector memory Tfh cells were significantly lower in the csDMARDs + bDMARDs treatment group than in untreated group. CD19+CD27+IgD+pre-switched memory B cells were higher in the csDMARDs and csDMARDs + bDMARDs treatment groups, whereas CD19+CD27+IgD-switched memory B cells were significantly lower than in untreated group. Ruminococcaceae_Ruminococcus was negatively correlated with CD19+CD27+IgD+ pre-switched memory B cells but positively correlated with CD4+CD45RO+CCR7-CXCR5+effector memory Tfh and CD19+CD27+IgD-switched memory B cells in patients with RA treated with DMARDs. ConclusionThe gut microbiota, memory Tfh cells, memory B cells, and cytokines of patients with RA changed significantly under different treatment regimens and had certain correlations with the clinical indicators of RA.

Impact of body composition on clinical outcomes in patients with active radiographic axial spondyloarthritis under biological therapy.

To assess the association of body composition, evaluated by bioimpedance analysis (BIA), with disease activity, physical function, and mobility in patients with axSpA undergoing bDMARD treatment for one year. Patients with AS (radiographic axSpA) were enrolled in an extension of the German Spondyloarthritis Inception Cohort (GESPIC). Patients were required to be candidates for bDMARD therapy at baseline presenting high disease activity despite previous treatment with nonsteroidal anti-inflammatory drugs. Outcomes (disease activity, function, and mobility) and body composition parameters were assessed at baseline and every 6 months thereafter. Body composition was assessed by BIA. The association between body composition parameters and outcomes over 1 year was analyzed using longitudinal generalized estimating equations. Seventy-four patients with radiographic axSpA were included in current analysis with a mean age of 36.5 years, disease duration of 6.2 years and ASDAS-CRP score of 3.4 at baseline. Fat mass value and fat mass index were positively associated with disease activity (ASDAS: ß = 0.01, 95% CI [-0.01, 0.03] and ß = 0.04, 95% CI [-0.01, 0.08], respectively) and functional disability (BASFI). Visceral adipose tissue (VAT) was associated with reduced spine mobility (BASMI: ß = 0.20, 95% CI [0.07, 0.33]). Additionally, increase in VAT and fat mass parameters was linked to worse disease activity and functional disability in women, while they were strongly associated with reduced spinal mobility in men. Higher levels of body fat and VAT were positively associated with increased disease activity, functional disability, and reduced spinal mobility in patients with radiographic axSpA treated with bDMARDs.

Predicting Flare in Patients With Rheumatoid Arthritis in Biologic Induced Remission, on Tapering, and on Stable Therapy.

The tapering of biologic disease-modifying antirheumatic drug (b-DMARD) therapy for patients with rheumatoid arthritis (RA) in stable remission is frequently undertaken, but specific guidance on how to successfully taper is lacking. The objective of this study is to identify predictors of flare in patients in stable b-DMARD-induced clinical remission, who did or did not follow structured b-DMARD tapering. Patients with RA receiving b-DMARD treatment who had achieved sustained remission according to a Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) <2.6 for ≥6 months were offered tapering. Clinical, ultrasound (US) (total power Doppler [PD]/grayscale abnormalities), CD4+ T cell subsets, and patient-reported outcomes (PROs) were collected at inclusion. The primary endpoint was the occurrence of flare (loss of DAS28-CRP remission) over 12 months. Logistic regression analyses identified predictors of flare. Dichotomization into high/low-risk groups was based on 80% specificity using the area under the receiving operator curve (AUROC). Of 63 patients choosing tapering, 23 (37%) flared compared with 12 of 60 (20%) on stable treatment (P = 0.043). All patients who flared regained remission upon reinstating treatment. In the tapering group, flare was associated with lower regulatory T cell (Treg) (P < 0.0001) and higher CRP levels (P < 0.0001), erythrocyte sedimentation rate (P < 0.035), and inflammation-related cells (IRCs) (P = 0.054); stepwise modeling selected Tregs (odds ratio [OR] = 0.350, P = 0.004), IRCs (OR=1.871, P = 0.007), and CRP level (OR=1.577, P = 0.004) with 81.7% accuracy and AUROC=0.890. In the continued therapy group, modeling retained the tender joint count, total PD, and visual analog scale pain score, with 82.1% accuracy and AUROC=0.899. Most patients in the study were considered low risk of flare (80 of 123 patients [65%]). Only 5 of 37 (13.5%) of the low-risk patients who tapered flared, which was notable compared with the continued therapy group (20% flare). Flare on tapering b-DMARDs was predicted by lower Tregs and elevated inflammation biomarkers (IRCs/CRP level); flare on continued b-DMARDs was associated with raised pain parameters and US inflammation. Knowledge of these biomarkers should improve outcomes by targeted selection for tapering, and by increased monitoring of those on continued therapy predicted to flare.

Predictors at diagnosis for start of biologic disease-modifying antirheumatic drugs in patients with early rheumatoid arthritis: a cohort study

ObjectivesTo investigate the relation between patient characteristics at rheumatoid arthritis (RA) diagnosis and subsequent initiation of treatment with biologic disease-modifying antirheumatic drugs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs).DesignA retrospective cohort...

The efficacy of tofacitinib combined with bDMARDs in the treatment of ankylosing spondylitis patients with inadequate response to bDMARDs: a retrospective study

IntroductionAnkylosing spondylitis(AS) is a chronic inflammatory rheumatic disease primarily affecting the spine and sacroiliac joints. While biologic disease-modifying antirheumatic drugs(bDMARDs) and targeted synthetic DMARDs(tsDMARDs) are popular treatments for AS, there is limited research on their combined use. This study examined a cohort of AS patients who demonstrated inadequate response to bDMARDs and subsequently initiated combination therapy with tofacitinib in conjunction with bDMARDs, assessing both the efficacy and safety profile of this therapeutic approach.MethodsIn this study, we retrospectively collected the electronic medical records (EMR) of 15 adult patients with AS who were admitted to the Fourth Affiliated Hospital Zhejiang University School of Medicine between January 2018 and June 2022. All patients had received at least one bDMARD treatment for more than three months and still exhibited moderate to high disease activity. Tofacitinib 5 mg bid was added to their original biological treatment. Treatment was continued for a minimum of 12 weeks following the initiation of combination therapy. Changes in ASDAS-CRP and BASDAI scores at week 12 were collected and analyzed from baseline, while changes in C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) at weeks 4, 8, and 12 were also collected and analyzed.ResultsAfter 12 weeks of treatment, the overall ASDAS-CRP score decreased significantly from a baseline of 3.82 ± 1.47 (2.83 ~ 4.99) to 1.47 ± 0.48 (0.75 ~ 2.44), with remission achieved by 7 patients (46.7%) and low disease activity achieved by 5 patients (33.3%). The overall BASDAI score also showed significant improvement, decreasing from a baseline of 5.11 ± 1.42 (3.25 ~ 7 0.75) to 1.28 ± 0.70(0.20 ~ 2.55). Additionally, both ESR and CRP levels decreased significantly during the course of treatment without any reported adverse events leading to discontinuation.ConclusionTo a certain extent, our findings provide some evidence supporting the efficacy and safety of the combination of bDMARD and JAK inhibitor tofacitinib in AS patients with inadequate response to bDMARD monotherapy. It effectively controls disease activity while maintaining a relatively low and manageable incidence of adverse events. Further prospective randomized controlled trials with large sample sizes are anticipated to provide evidence-based medical support.

The impact of bDMARDs on postoperative complications in patients with rheumatoid arthritis: A systematic review and meta-analysis.

The influence of biological disease-modifying antirheumatic drugs (bDMARDs) on postoperative surgical site infection (SSI) and venous thromboembolism (VTE) in patients with rheumatoid arthritis (RA) has not yet been clarified. A systematic literature search was performed using PubMed, Web of ScienceTM, Scopus, and The Cochrane Library databases to identify eligible studies published up to August 2023. All studies comparing postoperative SSI or VTE rates in RA patients with or without bDMARD treatment were included. The protocol for this study was registered in PROSPERO (CRD42021246264) and is available on the University of York website. Overall, 20 studies with 71,885 RA patients and 6 studies with 7918 RA patients were included for postoperative SSI and VTE comparisons, respectively. Patients treated with bDMARDs had significantly higher rates of postoperative SSI than those without treatment (odds ratio 1.50, 95% confidence interval 1.23-1.83, P < .0001). However, these significant differences disappeared in the analysis restricted to 9 studies involving non-tumor necrosis factor α inhibitors. The use of bDMARDs seemed to increase the rate of postoperative VTE (odds ratio 2.20, 95% confidence interval 1.30-3.72, P = .003). A subgroup analysis showed that postoperative osseous complications were significantly less frequent in RA patients with bDMARD treatment than in those without treatment. RA patients treated with bDMARDs had an increased risk of not only postoperative SSI but also VTE. While bDMARD usage merits appropriate attention, there might be positive aspects as well. Further data will be needed to confirm the postoperative risks of bDMARD usage in RA patients.

Comparative cardiovascular safety with janus kinase inhibitors and biological disease-modifying antirheumatic drugs as used in clinical practice: an observational cohort study from Sweden in patients with rheumatoid arthritis

ObjectivesTo compare the incidence of cardiovascular (CV) events in rheumatoid arthritis (RA) treated with janus kinase inhibitors (JAKi), tumour necrosis factor inhibitors (TNFi), or other biological disease-modifying antirheumatic drugs (bDMARDs),...

Comparative Effectiveness, Time to Discontinuation, and Patient-Reported Outcomes with Baricitinib in Rheumatoid Arthritis: 2-Year Data from the Multinational, Prospective Observational RA-BE-REAL Study in European Patients.

RA-BE-REAL is a 3-year, multinational, prospective, observational study of adult patients with rheumatoid arthritis (RA) evaluating time to discontinuation of initial RA treatment along with patient baseline characteristics. This study's primary objective was to assess the time to discontinuation of initial baricitinib, any other targeted synthetic disease-modifying anti-rheumatic drug (tsDMARD), or any biologic disease-modifying anti-rheumatic drug (bDMARD) treatment for all causes (excluding sustained clinical response) over 24 months in a European population. Patients initiated treatment with baricitinib (cohortA) or any bDMARD or tsDMARD (cohortB) for the first time. This study's primary objective was to assess the time to discontinuation of initial baricitinib, any other targeted synthetic disease-modifying anti-rheumatic drug (tsDMARD), or any biologic disease-modifying anti-rheumatic drug (bDMARD) treatment for all causes (excluding sustained clinical response) over 24months in a European population. Comparative effectiveness analyses, over 24months, included time to treatment discontinuation for all causes (excluding sustained clinical response), percentage of patients achieving Clinical Disease Activity Index (CDAI) remission or low disease activity (LDA), as well as mean changes from baseline for CDAI, pain visual analogue scale, and the Health Assessment Questionnaire-Disability Index (HAQ-DI). For this European subpopulation, comparative analyses were performed using a frequentist model averaging (FMA) framework based on a data-driven machine learning causal inference approach to compare time to discontinuation, effectiveness, rates of remission or LDA, and patient-reported outcomes over 24months comparing baricitinib with TNFi, as well as non-TNFi and tsDMARD grouped as other mechanism of action (OMA) drugs. In the European sample of RA-BE-REAL, patients with RA treated with baricitinib experienced fewer discontinuations in comparison to those treated with tumour necrosis factor inhibitors or OMA. Overall, patients naïve to b/tsDMARDs achieved a higher rate of LDA and remission compared with experienced patients. A significantly greater proportion of patients treated with baricitinib achieved LDA compared with b/tsDMARDs. This real-world data can better inform clinicians about baricitinib effectiveness and drug survival when prescribing treatment for patients with RA across different subpopulations.

Carriers of HLA-DRB1*04:05 have a better clinical response to abatacept in rheumatoid arthritis

HLA-DRB1 shared epitope risk alleles are the strongest genetic risk factors for rheumatoid arthritis (RA) and potential biomarkers for treatment response to biological disease-modifying antirheumatic drugs (bDMARDs). This study aimed to investigate the association between treatment response and individual HLA-DRB1 alleles in RA patients receiving different bDMARDs. We recruited 106 patients with active RA who had started abatacept, tocilizumab, or TNF inhibitors as a first-line bDMARDs. We examined the relationship between Simplified Disease Activity Index (SDAI) improvement at 3 months and HLA-DRB1 allele carriage. The results revealed that the HLA-DRB1*04:05 allele, a shared-epitope allele, was significantly associated with better SDAI improvement only after abatacept treatment (SDAI improvement 28.5% without the allele vs 59.8% with allele, p = 0.003). However, no significant association was found with other treatments. Both multivariate linear regression and mediation analysis confirmed that the HLA-DRB1*04:05 allele was independently associated with abatacept treatment response, regardless of anti-CCP antibody titers. The study concluded that in patients with RA receiving their first-line bDMARD treatment, carrying the HLA-DRB1*04:05 allele was associated with better SDAI improvement specifically in abatacept-treated patients. These disease-risk HLA alleles have the potential to serve as genomic biomarkers for predicting treatment response with co-stimulation blockage therapy.