TNF Inhibitors Research Articles

Treatments Used Among Patients with Psoriasis: A First Look at a New Patient-Centered Psoriasis Registry

Introduction: Psoriasis management in the US has changed substantially, with increasing treatment options including new topical, oral, and biologic medications. The objective of this study was to examine the demographics, disease characteristics, and treatment usage in the first patients enrolled in the new patient-centered psoriasis registry, the FORWARD Psoriasis Registry. Methods: Adult patients with psoriasis were recruited from dermatology offices as part of a national practice group, through a patient support program for deucravacitinib, and online from the FORWARD registry website between August and December 2023. Patients were not required to be on therapy for psoriasis. We descriptively report demographics, disease characteristics, and current treatments at enrollment. Results: A total of 702 patients met inclusion criteria and completed the full enrollment questionnaire. Mean age was 53 years and 66% were female; mean BMI was 30 (SD 7); 88% self-reported as White and 6% as Hispanic. A diagnosis of psoriatic arthritis was reported by 28%. Most (75%) had private insurance. Median psoriasis duration was 10 (IQR 3–23) years. 85% had plaque psoriasis, 19% guttate, 14% inverse, 6% generalized pustular, and 3% erythrodermic. Body surface area as assessed by the PREPI questionnaire was minimal (<1% BSA) in 21%, mild (1%–2%) in 39%, moderate (3%–10%) in 34%, and severe (>10%) in 6%. The most commonly used therapies included IL-23 inhibitors (11%), IL-17 inhibitors (8%), apremilast (7%), and TNF inhibitors (5%). Additionally, 14% of the cohort were using deucravacitinib; 62% reported using topicals, and 48% reported use of any systemic agent.Conclusion: The FORWARD psoriasis registry represents a new patient-centered approach and proof of concept for studies seeking to understand the natural history of the disease, treatment outcomes, and treatment needs relevant for individuals with psoriasis, and long-term outcomes related to comorbidities.

Real-World Switch Rates of Risankizumab and Other Biologics in Psoriasis Patients With Psoriatic Arthritis

Background: Psoriatic patients often experience issues with lack of therapeutic efficacy and intolerance, which may result in high levels of treatment switching. This study examined real-world, 12-month switch rates and patient characteristics associated with treatment switching in patients with both PsO and PsA treated with risankizumab and other biologics. Methods: This analysis used the Merative MarketScan® Databases (2016–2024) to identify adults from the US who had ≥2 medical claims for PsO, 1 claim for PsA and did not have any other autoimmune condition in the 6 months pre- and post-index period. Patients must have initiated a PsO-approved biologic and have continuous insurance benefits for ≥6 months before and ≥12 months after the biologic initiation date. Switch rates were defined as the proportion of patients who switched to a new biologic or advanced oral in the 12-month follow-up after treatment initiation. Discontinuation and non-adherence were not included in the switch definition. Switch rates were compared between biologics with sufficient sample size (n 100). Univariate logistic regression analyses were conducted to compare switch rates for risankizumab versus other biologics. Multivariate logistic regression analyses were performed to examine the impact of baseline demographic and treatment characteristics on switch rates and determine predictors of switching. Results: Among 3032 patients, mean age at baseline was 47.4 (SD 10.78) years and 55.4% were female. Overall treatment switch rate at 12-month follow-up was 24.9% (756/3032). Of those treatments with sufficient sample size, patients receiving risankizumab had the lowest switch rate (7.3%; 15/206) compared to all other biologics, including other IL-23 inhibitors (guselkumab 16.7%, P=0.0029), IL-17 inhibitors (ixekizumab 22.4%, P<0.0001; secukinumab 23.7%, P<0.0001), TNF inhibitors (adalimumab 28.3%, P<0.0001; etanercept 35.8%, P<0.0001), and IL-12/23 inhibitors (ustekinumab 22.4%, P<0.0001). Results were similar in multivariate logistic regression analyses after adjusting for variations in baseline characteristics. Predictors of switching at 12 months included female sex (adjusted odds ratio [aOR] [95% CI]: 1.63 [1.36, 1.94]; P<0.0001), baseline anxiety or depression (aOR [95% CI]: 1.47 [1.21, 1.80]; P=0.0001), baseline major adverse cardiovascular event (aOR [95% CI]: 1.47 [1.15, 1.88]; P=0.0023), and prior targeted immunomodulator (TIM) use (aOR [95% CI]: 1.45 [1.20, 1.74]; P=0.0001). Conclusion: In a real-world setting, switching was common among psoriasis patients with PsA. Risankizumab showed the lowest rate of treatment switching at 12 months, compared with all other biologics. Sex, comorbidities, and prior TIM use were predictors of higher switch rates.

Precision Medicine Proof-of-Concept Study of a TNF Inhibitor in FSGS and Treatment-Resistant Minimal Change Disease

Background: Focal segmental glomerulosclerosis (FSGS) and treatment-resistant minimal change disease (TR-MCD) are heterogeneous disorders with subgroups defined by distinct underlying mechanisms of glomerular and tubulointerstitial injury. A non-invasive urinary biomarker profile has been generated to identify patients with intra-kidney tumor necrosis factor (TNF)-activation and to predict response to anti-TNF treatment. We conducted this proof-of-concept, multi-center, open-label clinical trial to test the hypothesis that in patients with FSGS or TR-MCD and evidence of intra-renal TNF activation based on their biomarker profile, short-term treatment with adalimumab would reverse the elevated urinary excretion of MCP-1 and TIMP-1. Methods: Patients with FSGS or TR-MCD, eGFR>30 ml/min/1.73 m2, urine protein:creatinine ratio (UPCR) ≥1.5 g/g, and age 6-80 year were eligible for this trial. Adalimumab, 20-40 mg, was administered via subcutaneous injection, every 2 weeks for 5 doses. Participants were evaluated at weeks 0 (Baseline), 2, 8, and 10. Excretion of urinary (u) uMCP-1, uTIMP-1, uEGF, and plasma MCP-1 were measured at each visit. Results: Seven participants were enrolled, with median baseline UPCR 12.1 mg/mg (IQR: 2.2, 18.6), serum albumin 2.4 g/dL (IQR: 2.0, 2.8), and eGFR 57 mL/min/1.73 m2 (IQR: 44, 96). Based on self-report, they received all prescribed doses of adalimumab. The patients with the most favorable response based on the changes in urinary biomarkers had the best preserved kidney parenchyma based on uEGF excretion. Conclusions: Precision medicine trials are feasible in rare glomerular disorders. In this pilot study, adalimumab resulted in a heterogenous response of the candidate mechanistic-predictive biomarkers of TNF-mediated inflammation in patients with FSGS or TR-MCD. A reduction was seen in a subgroup of patients with preserved kidney parenchyma. The findings may reflect the challenge to reverse chronic injury at advanced stages of kidney disease or insufficient intra-renal target engagement with the intervention drug dose.

Effect of Biological Therapy for Psoriasis on the Development of Psoriatic Arthritis: A Population-Based Cohort Study.

Evidence comparing the impact of various biologics for psoriasis on the progression to psoriatic arthritis (PsA) is limited. We therefore assessed the risk of PsA associated with interleukin (IL)-23 inhibitor, IL-17 inhibitor, or IL-12/23 inhibitor use compared with tumor necrosis factor (TNF) inhibitor use among patients with psoriasis. This population-based cohort study used the nationwide claims database from South Korea (2007-2023). New users of IL or TNF inhibitors with psoriasis who did not have PsA or other inflammatory arthritis were categorized into each class of the IL inhibitors for comparison with TNF inhibitor users. The outcome measured was the development of incident PsA. We calculated multinomial overlap weights to balance predefined covariates. Hazard ratio (HR) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. We identified 9499 patients with psoriasis (mean age 45.1 years; 33.6% female), of whom 3913 (41.2%), 2126 (22.4%), 2773 (28.8%), and 727 (7.7%) were exposed to IL-23 inhibitor, IL-17 inhibitor, IL-12/23 inhibitor, and TNF inhibitor, respectively. PsA developed in 281 (3.0%) patients during 23,275 person-years. The weighted HR for any IL inhibitors was 0.40 (95% CI 0.25-0.62), with specific HRs of 0.22 (95% CI 0.13-0.37), 0.47 (95% CI 0.28-0.80), and 0.46 (95% CI0.29-0.74) for IL-23 inhibitor, IL-17 inhibitor, and IL-12/23 inhibitor, respectively. IL-23 inhibitors exhibited the greatest rate difference of - 2.61 (95% CI - 3.67 to - 1.55) cases of PsA per 100 person-years. The use of IL inhibitors, particularly IL-23 inhibitors, compared with TNF inhibitors, was associated with a lower risk of developing PsA.

Paradoxical deterioration during treatment of tuberculous meningitis responded to infliximab but not to steroids

Paradoxical deterioration in patients with tuberculous meningitis is a significant diagnostic and treatment challenge. We present the case of a 55-year-old previously healthy male, human immunodeficiency virus (HIV)-negative, presenting with headache, fever, agitation and slurred speech, who was ultimately diagnosed with tuberculous meningoencephalitis confirmed by cerebrospinal fluid polymerase chain reaction positive for Mycobacterium tuberculosis complex. After initiation of a standard antitubercular therapy combined with glucocorticoids, the patient experienced an initial neurological improvement. However, after 3 months of therapy, he had a major stroke with neurological deterioration, clinically and radiologically attributable to a paradoxical deterioration or an immune reconstruction syndrome as described in HIV-positive patients. Due to the persistence of inflammatory symptoms and radiological evidence of worsening tuberculomas despite ongoing antituberculosis therapy, off-label use of the tumour necrosis factor (TNF) inhibitor infliximab was initiated. The patient received three doses of infliximab at 5 mg/kg at monthly intervals, which led to marked clinical and radiological improvement. Follow-up magnetic resonance imaging showed regression of lesions, and the patient was eventually discharged with a significant recovery of motor and speech functions. This case underscores the potential of TNF inhibitors in managing severe cases of paradoxical deterioration in patients with tuberculous meningitis, challenging existing treatment paradigms and suggesting a need for further research into the pathophysiology and treatment of this condition.

Psoriatic arthritis phenotype clusters and their association with treatment response: a real-world longitudinal cohort study from the psoriatic arthritis research consortium

ObjectivesTo identify phenotype clusters and their trajectories in psoriatic arthritis (PsA) and examine the association of the clusters with treatment response in a real-world setting.MethodsIn the multicentre PsA Research Consortium...

Ustekinumab Biosimilars

Ustekinumab is a fully human IgG1k monoclonal antibody that binds with high affinity and specificity to the p40 subunit of interleukins (IL-) 12 and 23, inhibiting their activity by preventing binding to their receptors. The European extension of the patent (Supplementary Protection Certificate) of ustekinumab expired on 20 July 2024. Biosimilar alternatives to ustekinumab are now an additional option for treating patients. The efficacy data for this drug in moderate-to-severe psoriasis obtained both from clinical trials and indirect comparisons through meta-analyses, are superior to those of etanercept and adalimumab, and its safety profile is more favorable than that of tumor necrosis factor (TNF) inhibitors. Several ustekinumab biosimilars have already been approved by regulatory agencies: between October 2023 and October 2024, Wezlana® (Amgen ABP 654), Uzpruvo® (Alvotech AVT04) and Pyzchiva® (Samsung/Bioepis SB17) have been approved by both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). SteQeyma® (Celltrion Healthcare CT-P43) was approved by the EMA in August 2024. Otulfi® (Fresenius Kabi/Formycon) was approved by the FDA in October 2024. Several other potential biosimilar candidates are under development, including BAT2206 (Bio-Thera), DMB-3115 (Dong-A ST), QX001S (Qyuns Therapeutic), BFI-751 (BioFactura), NeuLara (Neuclone), ONS3040 (Oncobiologics), and BOW090 (Epirus Biopharmaceuticals). In most cases, these monoclonal antibodies are expressed in cell lines (e.g., Chinese Hamster Ovary, CHO) different from those used for the originator (Sp2/0 spleen cell murine myeloma); of note, the cell line of origin is not a requirement for biosimilarity in the totality-of-evidence comparison exercise and may facilitate the production and reduce the immunogenicity of biosimilars originated in CHO cultures. This narrative review summarizes the available data on characteristics of the full comparability exercises and comparative clinical trials of these drugs.

Immunogenicity of Therapeutic Antibodies Used for Inflammatory Bowel Disease: Treatment and Clinical Considerations.

The introduction of tumor necrosis factor inhibitors has led to a paradigm shift in the management of inflammatory bowel disease (IBD). The subsequent introduction of both anti-integrins and cytokine blockers has since expanded the biologic armamentarium. However, immunogenicity, defined as the production of anti-drug antibodies (ADAs) to the prescribed biopharmaceutical, means a significant fraction of patients exposed to biologic agents will experience a secondary loss of response to one or more of the drugs. In clinical settings, immunogenicity may be caused by several factors, both patient related (e.g., underlying chronic disease, systemic immune burden, including previous biologic therapy failure, and [epi]genetic background) and treatment related (e.g., dose and administration regimens, drug physical structure, photostability, temperature, and agitation). Here, we outline these elements in detail to enhance biopharmaceutical delivery and therapy for patients with IBD. Moreover, concurrent immunomodulator medication may reduce the risks of ADA generation, especially when using the chimeric drug infliximab. Summarizing the latest developments and knowledge in the field, this review aims to provide strategies to prevent ADA production and information on managing non-responsiveness or loss of response to biologics. Better understanding of the molecular mechanisms underlying the formation of ADAs and the critical factors influencing the immunogenicity of biopharmaceuticals may lead to improved health outcomes in the IBD community that may benefit both the individual patient and society through lower healthcare expenses.

The Persistence of Biologic Therapies for Psoriatic Arthritis: A Narrative Review.

Drug persistence is a crucial measure of long-term efficacy, safety, and patient satisfaction. Lack of persistence can increase healthcare costs and morbidity and mortality rates. This review aimed to consolidate available data on drug persistence for various biological treatments used as the primary intervention for psoriatic arthritis and identify factors associated with nonpersistence. Reports indicate variable 1-year persistence rates for biologic therapies, ranging from 37% to 73%. Specifically, tumor necrosis factor inhibitors have shown fluctuating 1-year persistence rates ranging from 32% to 85%. IL-12/23 and IL-23 inhibitors demonstrate persistence rates of 25% to 89%, whereas data for IL-17 and JAK inhibitors are more limited, ranging from 51% to 77%. Factors such as female sex and a higher burden of comorbidities have been associated with an increased risk of nonpersistence, although evidence regarding other factors remains scarce. The significant variability in reported persistence rates may be attributed to differences in treatment gaps and methodologies across studies. Addressing and mitigating the factors leading to nonpersistence is essential for improving treatment outcomes in psoriatic arthritis.

Analysis of periodontal status in Polish patients with rheumatoid arthritis treated with biological therapies

IntroductionPeriodontitis, characterized by inflammation affecting the tooth-supporting tissues, may increase the risk of rheumatoid arthritis (RA) or cardiovascular diseases. The aim of the study was to evaluate the periodontal status in RA patients and its impact on the inflammatory markers and red cell parameters obtained from complete blood laboratory tests to study the risk of cardiovascular disease development.Material and methodsThe cross-sectional study included 50 patients with RA treated with biologi­cal therapies: tumor necrosis factor inhibitors, interleukin-6 blockers. Rheumatoid arthritis disease activity was assessed with Disease Activity Score with 28-joint count (DAS28). The periodontal indices modified Approximal Periodontal Index, modified Papillary Bleeding Index, and Periodontal Screening Index (PSI) were used to assess patients’ periodontal status. Serum levels of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were used as inflammatory markers and a potential cardiovascular risk factor.ResultsNo statistically significant correlation was found between the periodontal status and RA activity. However, a statistically significant correlation was found between the CRP results and the PSI scores (<i>R</i> = –0.264510, <i>p</i> = 0.048837). Evaluation of the red cell parameters showed statistically significant differences in the markers of inflammation ESR (<i>R</i> = 0.369398, <i>p</i> = 0.008289) and CRP (<i>R</i> = 0.367405, <i>p</i> = 0.008672). Red cell distribution width values were also correlated with RA activity (<i>R</i> = 0.286387, <i>p</i> = 0.043769) and duration of the disease (<i>R</i> = 0.339425, <i>p</i> = 0.015889).ConclusionsA satisfactory periodontal status was found in most of the study group. Increased CRP levels in patients with periodontitis may indicate the negative impact of periodontal status on the general clinical condition of the patient.

Cardiovascular risk according to biological agent exposure in patients with ankylosing spondylitis: a nationwide population-based study.

Patients with ankylosing spondylitis (AS) have a higher risk of cardiovascular events than controls. Although biological disease-modifying anti-rheumatic drugs (bDMARDs) are efficacious in treating AS, their effect on cardiovascular risk remains unclear. This study evaluated the effect of tumour necrosis factor inhibitors (TNFis) and interleukin-17 inhibitors (IL-17is) on cardiovascular risk in patients with AS. Data of 43,502 patients diagnosed with AS from 2010 onwards and without prior history of cardiovascular events were extracted from the Korean nationwide database. Cardiovascular events were defined as incident myocardial infarctions or strokes. Patients were followed-up through 2021. The risk of cardiovascular events was compared between TNFis exposure (vs. bDMARDs non-exposure), IL-17is exposure (vs. bDMARDs non-exposure), and IL-17is exposure (vs. TNFis exposure), using time-dependent Cox models. The incidence rates of cardiovascular events during bDMARDs non-exposure, TNFis exposure, and IL-17is exposure were 18.66, 8.92, and 12.87 per 10,000 person-years, respectively. TNFis exposure (vs. bDMARDs non-exposure) was significantly associated with a lower risk of cardiovascular events (adjusted hazard ratio [aHR] = 0.697, 95% confidence interval [CI] = 0.499-0.973), whereas IL-17is exposure (vs. bDMARDs non-exposure) was not (aHR = 0.962, 95% CI = 0.134-6.920). The risk of cardiovascular events did not differ between IL-17is and TNFis exposures (aHR = 1.381, 95% CI = 0.189-10.087). TNFis exposure (vs. bDMARDs non-exposure) was associated with approximately 30% lower risk of cardiovascular events in patients with AS. IL-17is exposure had no significant association with the risk of cardiovascular events compared with bDMARDs non-exposure or TNFis exposure. Key Points • TNFis exposure was associated with a 30% lower cardiovascular risk in patients with AS. • IL-17is exposure had no significant association with cardiovascular risk in patients with AS. • TNFis could be the preferred bDMARD with regard to cardiovascular risk in patients with AS.

Precision Dosing of Intravenous Tocilizumab: Development of Pharmacokinetic Model-Derived Tapering Strategies for Patients With Rheumatoid Arthritis.

Tocilizumab targets the interleukin-6 receptor, and dosing is complex owing to its nonlinear clearance related to target binding. Therefore, tapering tocilizumab requires a different approach than that of tumor necrosis factor inhibitors (TNFi). This study aimed to identify these differences and enable personalized treatment of rheumatoid arthritis (RA) beyond TNFi therapy. A population pharmacokinetic model of intravenous tocilizumab was developed using data from a randomized controlled trial of dose tapering in patients with RA. Subsequent population-level Monte Carlo and individual Bayesian simulations were performed to create tapering strategies involving dose reduction and interval extension. The target trough concentration of tocilizumab was 5 mg/L. Finally, the drug savings were compared between the 2 methods. The pharmacokinetic of tocilizumab was described with a 2-compartment model with parallel linear (CL 0.20 L/d) and nonlinear (VM 5.2 mg/d, KM 0.19 mg/L) elimination. The linear clearance rate and central volume of distribution increased with lean body mass, and men exhibited higher clearance rates than women. The simulated concentration-time profiles demonstrated that, owing to nonlinear clearance, drug concentrations decreased more than dose-proportionally with lower doses. Tapering based on an individual Bayesian approach emerged as the most promising strategy, yielding a 39% reduction in drug use across virtual populations. Tapering strategies were developed for intravenous tocilizumab, offering potential application in patients with RA who have reached low disease activity or remission, pending clinical validation. The developed strategies demonstrate that the tapering of tocilizumab should be approached more carefully and in smaller steps than that of TNFi.

Minimal disease activity and associated factors in patients with psoriatic arthritis: cross-sectional study from a single center

IntroductionPsoriatic arthritis (PsA) is a heterogeneous disease with various manifestations such as dactylitis, enthesitis, spondylitis, and skin involvement. Minimal disease activity (MDA) has been successfully used in daily clinical practice and is considered a reasonable treatment target in patients with PsA. In this study, we aimed to evaluate the MDA status and associated factors in patients with PsA in our tertiary referral clinic.Material and methodsThis cross-sectional study included patients who met the CASPAR classification criteria and had at least 6 months of follow-up data between 2001 and 2021. Patients who met at least 5 of 7 criteria (tender joint count ≤ 1/68, swollen joint count ≤ 1/66, Psoriasis Area Severity Index [PASI] ≤ 1, Visual Analogue Scale [VAS] ≤ 15, patient global VAS ≤ 20, Health Assessment Questionnaire-Disability Index [HAQ-DI] ≤ 0.5, and enthesitis number ≤ 1) were considered to achieve MDA.ResultsData from 172 patients (61% female) were analyzed and included in the study. While most patients had polyarticular involvement (33.7%), mono-oligoarthritis was present in 30.2%, mixed type in 26.2%, isolated distal interphalangeal arthritis in 5.8%, isolated spondylitis in 2.9%, and arthritis mutilans in 1.2%. Overall, 95 (55.2%) of the patients were observed at MDA, which was lower in tumor necrosis factor inhibitor (TNFi) users compared to only conventional synthetic disease-modifying antirheumatic drug users. In univariate analysis, MDA was associated with higher patient age, longer psoriasis duration, late-onset PsA, and continued use of first TNFi. In multivariate analysis, higher patient age, late-onset PsA, and higher continuation rate of first TNFi were associated with MDA.ConclusionsIn the study, more than half of our patients achieved MDA status. A higher MDA rate was associated with a higher continuation rate at first-line TNFi treatment. The relatively large po­pulation who could not reach MDA status in our study indicates an unmet need for monitoring and treatment of PsA.

Impairment of regulatory T cell stability in axial spondyloarthritis: role of EZH2 and pSTAT5

Background and objectivesAxial spondyloarthritis (axSpA) is a chronic inflammatory disease involving the spine, peripheral joints, and entheses. Functional impairment of regulatory T cells (Treg) is linked to inflammatory diseases, but limited data is available regarding Treg involvement in axSpA. Treg stability refers to their ability to maintain their functions and characteristics in pro-inflammatory environments. EZH2 and phosphorylated STAT5 (pSTAT5) play a critical role in maintaining Treg stability. We aimed to characterize Treg stability in patients with axSpA.MethodsPeripheral blood mononuclear cells (PBMCs) from axSpA patients, either naïve from targeted therapy or treated by TNF inhibitors (TNFi), and from healthy donors (HD), were freshly isolated. Expression of stability (EZH2, pSTAT5) and suppressive (TNFR2 and CD39) markers by Treg was analyzed by flow cytometry.ResultsEZH2 expression by Treg was decreased in axSpA patients as compared to HD (p<0.01). Mechanistic study showed that inhibition of EZH2 attenuated Treg differentiation and suppressive phenotype in vitro. EZH2 was predominantly expressed by highly suppressive TNFR2+ and CD39+ Treg. Additionally, axSpA patients also exhibited a reduced frequency of pSTAT5+ Treg compared to HD (p<0.05), and pSTAT5+ Treg frequency increased at 3 months of TNFi treatment compared to baseline (p<0.05). This last result suggested a restoration of Treg stability upon TNFi treatment.ConclusionBy highlighting a deficient expression of EZH2 and pSTAT5 by Treg, we revealed an impaired Treg stability in axSpA. Deciphering the pathways influenced by these molecules is necessary to assess the potential therapeutic benefits of restoring Treg stability in axSpA.

COVID-19 vaccination-related delayed adverse events among people with rheumatoid arthritis: results from the international COVAD survey.

This study aimed to assess COVID-19 vaccination-related AEs in patients with rheumatoid arthritis (RA), in the COVID-19 Vaccination in Autoimmune Diseases (COVAD)-2study. An online international cross-sectional survey captured self-reported data on COVID-19 vaccination-related adverse events (AEs) in people with RA, autoimmune diseases (AIDs; rheumatic [r] and non-rheumatic [nr]) and healthy controls (HCs). The survey was circulated by the COVAD study group, comprising 157 collaborators across 106 countries, from February to June 2022. Delayed AEs among RA were compared with other rAIDs, nrAIDs and HCs using multivariable binary regression. A total of 7203 participants were included (1423 [19.7%] RA, 2620 [36.4%] rAIDs, 426 [5.9%] nrAIDs, 2734 [38%] HCs), with 75% female. Compared to HCs, individuals with RA reported higher overall major AEs [OR 1.3 (1.0-1.7)], and an increased number of several minor AEs. Compared to nrAIDs, people with RA had several increased reported minor AEs including myalgia and joint pain. People with active RA had increased major AEs [OR 1.8 (1.1-3.0)] and hospitalisation [OR 4.1 (1.3 - 13.3)] compared to inactive RA. RA patients without autoimmune comorbidities had significantly fewer major and minor AEs than those with other rAIDs. A decreased incidence of hospitalisation was seen in patients taking methotrexate or TNF inhibitors compared to patients not taking these medications. COVID-19 vaccination is associated with minimal to no risks of delayed AEs in patients with RA compared to HCs, and fewer compared to other rAIDs. Active RA and presence of co-existing rAIDs were associated with an increased risk of delayed AEs.

Predictors of the effectiveness to first-line CTLA4-Ig in patients with rheumatoid arthritis: the FIRST registry.

This study aimed to elucidate which bio-naïve patients with rheumatoid arthritis (RA) are suitable for treatment with CTLA4-Ig. This study enrolled 953 patients with RA who were administered their first biological disease-modifying antirheumatic drug (CTLA4-Ig, n = 328; tumour necrosis factor inhibitor [TNFi], n = 625) from July 2013 to August 2022. The primary outcome was the Clinical Disease Activity Index (CDAI) remission rate at week 24 in each group, adjusted using Propensity Score-based Inverse Probability of Treatment Weighting (PS-IPTW). After minimizing selection bias using PS-IPTW, the CDAI remission showed no significant difference between the CTLA4-Ig and TNFi groups (p= 0.464). Multivariable logistic regression analysis identified low baseline Health Assessment Questionnaire-Disability Index (HAQ-DI) scores as a contributing factor to the CDAI remission rate at week 24 in both groups, along with high baseline anti-citrullinated peptide antibody (ACPA) levels in the CTLA4-Ig group. However, among patients with high baseline HAQ-DI scores and low baseline ACPA levels (≦57.2), the CDAI remission rate was significantly higher in the TNFi group (29.8%) compared with the CTLA4-Ig group (5.9%, p< 0.0001). Among patients with high baseline HAQ-DI scores and ACPA levels (>57.2), the CDAI remission rate was significantly higher in the CTLA4-Ig group (35.6%) compared with the TNFi group (22.1%, p= 0.0057). Bio-naive RA patients with low HAQ-DI scores showed high treatment efficacy with no significant difference between CTLA4-Ig and TNFi. Among patients with high baseline HAQ-DI scores, TNFi and CTLA4-Ig were more likely to be effective in those with lower and higher baseline ACPA levels, respectively.

Sjögren's Syndrome and Ankylosing Spondylitis Association: A Case-Based Review.

Unlike restrictive pulmonary function and apical fibrobullous disease, diffuse interstitial lung disease is scarce in patients with ankylosing spondylitis (AS). We present a systematic review of the association between AS and SS. We also report a new case of SS revealed by interstitial lung disease in AS patients treated with tumor necrosis factor (TNF) inhibitors. The systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline using the MEDLINE and SCOPUS databases and included case reports and case series describing the association between AS and SS. There were sixty-three patients, including our case: 16 males and 47 females. The mean age was 49.2 years. The mean SpA duration was 14.1 years. The mean delay between SpA and SS was 12.8 years (0-27). SS was diagnosed after SpA in 62% of cases (n=39). It preceded SpA in 36.5% (n=23) and was concomitant with SpA in 1 case. All patients had sicca symptoms. MSGB showed focal sialadenitis grade III or grade IV in the Chisholm classification in 20 patients. Anti- nuclear antibody was positive in 75.8% of cases. Among them, anti-SSA and anti-SSB were positive in 44.4% and 35.3% of cases. Except for our patient, no patient had interstitial lung disease. SS extra glandular manifestations were reported in 12 cases. The occurrence of Sjögren's syndrome is uncommon in patients with ankylosing spondylitis. This association has been reported in the literature, suggesting a pathogenetic link between these two diseases. This association should be considered in ankylosing spondylitis patients with diffuse interstitial lung disease. Knowing this association is necessary for therapeutic adjustment. Our study has some limitations. Publication bias was the major bias in our study. Indeed, we only included case reports and case series describing the association between SpA and SS. We did not search for unpublished work. Moreover, the follow-up was not specified in most included articles.

TNF inhibitors increase risk of inflammatory CNS disorders

TNF inhibitors increase risk of inflammatory CNS disorders

Impact of patient characteristics on ASDAS disease activity state cut-offs in axial spondyloarthritis: results from nine European rheumatology registries.

To re-evaluate cut-offs for disease activity states according to the Axial Spondyloarthritis Disease Activity Score (ASDAS), and study the impact of sex, age, calendar time, disease and symptom duration on ASDAS and ASDAS cut-offs in a large contemporary cohort. Data from 2939 patients with axial spondyloarthritis (axSpA) starting their first tumour necrosis factor inhibitor in nine European registries were pooled and analysed. Receiver operating characteristic analyses were performed to identify cut-offs against external criteria. Six-month data including patient and physician global assessments, both ≤1 (0-10 integer scale), and Assessment of SpondyloArthritis International Society partial remission were used for separation of inactive disease (ID) from low disease activity (LDA), while patient and physician global ≤3 were applied as external criteria to separate LDA from high disease activity (HDA). Patient and physician global ≥6 were applied to separate HDA from very high disease activity in baseline data. The three ASDAS cut-offs identified to separate the four disease activity states in the overall patient population were <1.3, <2.0 and >3.5. Cut-offs for ID and LDA in women were higher (<1.5 and <2.0, respectively) than in men (<1.3 and <1.9), as were cut-offs in patients ≥45 years (<1.5 and <2.2) versus ≤34 years (<1.2 and <1.9) and 35-44 years (<1.3 and <1.8). Cut-offs were independent of calendar time and disease duration. Re-evaluation of ASDAS cut-offs for disease activity states in a large multi-national axSpA cohort resulted in cut-offs similar to those currently endorsed. Differences in cut-offs between sex and age groups for ID and LDA were observed, but the differences were minor.

Tofacitinib Safety and Effectiveness in Canadian Patients with Rheumatoid Arthritis by Cardiovascular Risk Enrichment: Subanalysis of the CANTORAL Study.

ORAL Surveillance, a post-authorisation safety study of patients with rheumatoid arthritis (RA) enriched for cardiovascular (CV) risk, demonstrated increased risk of major adverse CV events (MACE) and malignancies (excluding non-melanoma skin cancer [NMSC]) for tofacitinib versus tumour necrosis factor inhibitors (TNFi). This analysis of a real-world Canadian observational study evaluated tofacitinib safety/effectiveness in patients meeting or not meeting CV risk criteria. CANTORAL included patients with moderate-to-severe RA initiating tofacitinib (10/2017-07/2020; N = 504). Interim data (data-cut: 07/2021) were stratified as CV risk-enriched (CV+ ; patients ≥ 50 years with ≥ 1 additional CV risk factor) or not CV risk-enriched (CV-; ≥ 50years without additional CV risk factors and 18-49 years with/without CV risk factors). Safety and persistence were evaluated to month (M) 36. Effectiveness outcomes to M18 included Clinical Disease Activity Index (CDAI)-defined low disease activity (LDA)/remission (CANTORAL co-primary endpoints) and Disease Activity Score in 28 joints, C-reactive protein (DAS28-4[CRP]) < 3.2/ < 2.6. Overall, 272/232 patients were included in CV+ /CV- cohorts (full analysis set) (435/356 patient-years [safety analysis set]). Incidence rates (events/100 patient-years) in CV+ /CV- cohorts were 138.5/112.5 for treatment-emergent adverse events (AEs); 17.0/5.6for serious AEs; 1.2/0.3for deaths; 5.5/1.7 for serious infections; 1.4/1.1 for herpes zoster; 1.6/0.0for MACE; 2.1/0.3for malignancies (excluding NMSC); 0.7/0.6 for NMSC; 0.5/0.0 for venous thromboembolic events. Persistence was generally comparable between cohorts. In CV+ /CV- cohorts, at M6, CDAI LDA and remission rates were 51.5%/54.6% and 12.0%/19.6%; DAS28-4(CRP) < 3.2/ < 2.6 rates were 44.0%/39.3% and 31.5%/28.8%, respectively; effectiveness was generally maintained to M18. In concordance with studies of background risk, AEs were more common in patients with CV risk enrichment, particularly those aged ≥ 65 years. Tofacitinib effectiveness/persistence were generally similar regardless of CV risk enrichment. These findings support individualised treatment benefit-risk assessment, including CV assessment/management, to optimise RA outcomes.