Biologic Disease-modifying Antirheumatic Drugs Research Articles

Age-Related Variations in Treatment Patterns for Axial Spondyloarthritis

Aim: This study examines treatment patterns and preferences among patients diagnosed with Axial Spondyloarthritis (AxSpA) across different age groups. Material and Method: Ankara Bilkent City Hospital registry enabled a comprehensive cross-sectional analysis of 2,811 patients stratified into three age groups: 18-40, 41-55, and over 55 years. These groups were compared in terms of their treatments. Results: Our findings indicate an increasing prevalence of female patients and comorbidities with age. Medication usage patterns showed a trend towards increased use of Methotrexate and Colchicine with age, while Sulfasalazine and Leflunomide were more commonly prescribed in older age groups. Notably, the use of biologic Disease-Modifying Anti-Rheumatic Drugs (bDMARDs), including anti-Tumor Necrosis Factor (anti-TNF)", "anti-Interleukin (anti-IL) agents, demonstrated a declining trend with advancing age, though not reaching statistical significance. This trend was also reflected in gender-specific treatment distributions, where no significant difference was found in bDMARDs administration among patients over 55 years, contrasting with a higher usage rate in younger male patients. Conclusion: Our study highlights a shift towards more conservative treatment approaches, such as increased conventional synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs) use in older patients, likely due to their safety profile and the specific challenges associated with treating older adults, including higher comorbidity rates and medication side effects. These findings emphasize the need for personalized treatment strategies and suggest potential adjustments in clinical practices to better accommodate the aging population, advocating for ongoing research to optimize treatment efficacy and safety for elderly patients with AxSpA.

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.

Drug-induced lung disease: a narrative review.

Drug-induced lung disease (DILD) encompasses a broad, highly heterogeneous group of conditions that may occur as a result of exposure to numerous agents, such as antineoplastic drugs, conventional or biological disease-modifying antirheumatic drugs, antiarrhythmics, and antibiotics. Between 3% and 5% of prevalent cases of interstitial lung diseases are reported as DILDs. The pathogenesis of lung injury in DILD is variable, multifactorial, and often unknown. Acute presentation is the most common, can occur from days to months after the start of treatment, and ranges from asymptomatic to acute respiratory failure. The CT patterns are varied and include ground-glass opacities, organizing pneumonia, and diffuse alveolar damage. Notably, there are no clinical manifestations or CT patterns specific to DILD, which makes the diagnosis quite challenging and necessitates a high index of suspicion, as well as the exclusion of alternative causes such as infection, cardiac-related pulmonary edema, exacerbation of a preexisting ILD, and neoplastic lung involvement. Discontinuation of the offending medication constitutes the cornerstone of treatment, and corticosteroid treatment is usually necessary after the onset of clinical manifestations. The prognosis varies widely, with high mortality rates in severe cases. A history of medications related to pulmonary toxicity in patients with new-onset respiratory symptoms should prompt consideration of DILD as a potential underlying cause.

A Meta-Analysis Examining the Effect of Perioperative Biologic Disease-Modifying Anti-Rheumatic Medications on Postoperative Wound Complications in Various Orthopedic Surgeries.

This meta-analysis was designed to compare the risk of postoperative wound complications in various orthopedic surgeries (OSs) affected by the perioperative use of biologic disease-modifying anti-rheumatic drugs (bDMARDs). The odds ratio (OR) and mean difference (MD), with 95% confidence intervals (CIs), were calculated using dichotomous or continuous random or fixed-effect models, based on the meta-analysis data. This study incorporated 14 investigations conducted between 2005 and 2023, encompassing a total population of 19,021 individuals undergoing diverse OSs. Participants who continued their bDMARDs exhibited a substantially higher incidence of postoperative surgical site infections (OR, 1.39; 95% CI, 1.12-1.72, p = 0.002) compared to those who withheld bDMARDs. However, the study did not find any statistically significant difference between the continuation or withholding of bDMARDs regarding delayed wound healing (OR, 2.02; 95% CI, 1.00-4.06, p = 0.05) or disease flares (OR, 0.59; 95% CI, 0.28-1.25, p = 0.17). The results show that patients who continued their bDMARDs had a notably higher incidence of postoperative surgical site infections. However, no significant differences were observed in delayed wound healing or disease flares when compared to those who withheld bDMARDs. It is important to acknowledge the limitations of this analysis, such as the relatively small number of participants and the limited number of studies available for certain comparisons, which may impact the validity of the findings.

Anakinra in the management of adult-onset still's disease: a single-center experience.

Adult-onset Still's disease (AOSD) is a rare systemic autoinflammatory disorder of unknown etiology characterized by systemic inflammation, high fever, salmon-colored skin rash, arthralgia, and arthritis. Patients with AOSD may also present with elevated inflammatory markers, hyperferritinemia, anemia, leukocytosis, hepatosplenomegaly, and lymphadenopathy. Glucocorticoids and biological disease-modifying anti-rheumatic drugs, including the anti-interleukin-1 agent anakinra, are used in the management of AOSD. This retrospective single-center study included patients with AOSD who were registered at our tertiary center, and received anakinra treatment. The primary outcome of our study was the proportion of patients who achieved complete remission of disease-related clinical and laboratory complications. The glucocorticoid treatment profiles of the included patients before and after anakinra treatment were also analyzed. The occurrence of serious and non-serious adverse events was recorded to analyze the safety profile of anakinra. Thirty-four patients with AOSD, including 25 females (73.5%), were enrolled in the study. Twelve patients (35.3%) achieved complete remission and 14 patients (41.2%) achieved partial remission after anakinra treatment. Eight patients (23.5%) did not response to anakinra. Anakinra significantly decreased the number of patients receiving glucocorticoid treatment [33 (97%) vs. 22 (64.7%), p < 0.001] and the mean daily glucocorticoid dose [19 ± 13.5mg vs. 4.6 ± 5.8mg, p < 0.001]. Mild adverse events occurred in 11 patients (32.3%) with injection site reactions being the most common. One patient (2.9%) was diagnosed with tuberculosis within the treatment period. Anakinra is an effective and generally safe option for biological treatment initiation in the management of AOSD.

Measurable Outcomes of an Ophthalmology and Rheumatology Coordinated Care Clinic.

Evaluate the impact of an Ophthalmology/Rheumatology multidisciplinary clinic for patients with anterior uveitis by comparing outcomes between those who received traditional care (TC) versus coordinated care (CC). We conducted a retrospective cohort study of children with anterior uveitis from a pediatric tertiary care center between 2013 and 2022. Standard descriptive statistics were used; survival analyses explored differences in cohort disease activity and biologic DMARDs use. Steroid use by cohort was compared using generalized estimating equation model with Poisson distribution and log link. Complications were compared using logistic regression. Number of visits in each cohort were assessed using Poisson generalized estimating equation model adjusted for complications. We studied 215 anterior uveitis patients: 66% were female, 53% had JIA, 23% were idiopathic, with a median age at diagnosis of eight (interquartile range (IQR) 5-12). CC was associated with a 60% higher hazard (HR = 1.6; p < 0.01) of reaching disease control, when controlling for time since diagnosis and anterior chamber cell counts at beginning of disease activity. CC was associated with starting biologic DMARDs faster than TC (p < 0.01). Compared to TC, CC had a 96% lower rate of corticosteroid use per appointment within the first year (p< 0.01). The visit rate was 64% lower for CC, when controlling for total complications per patient. Patients who received multidisciplinary care had better outcomes than patients who received traditional care. Limitations include different cohort-start times and absence of defined criteria for coordinated care referral.

Decision Aid-Led Tapering of Biologic and Targeted Synthetic Disease-Modifying Antirheumatic Drugs in Rheumatoid Arthritis: A Qualitative Study.

To explore the experiences and perspectives of patients and rheumatologists on decision aid (DA)-led tapering of advanced therapy in rheumatoid arthritis (RA). Semistructured interviews were completed with patients and rheumatologists, embedded within a pilot study of DA-led tapering (ie, dose reduction) of biologic disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) in RA. All patients were in sustained (≥ 6 mos) remission and had chosen to reduce their therapy after a DA-led shared decision with their rheumatologist. The rheumatologists included those participating in the pilot (n = 4), and those who were not (n = 8). Reflexive thematic analysis of audiotaped and transcribed interviews identified themes in the group experiences. Patients (n = 10, 6 female) unanimously found the DA easy to understand and felt confident in shared decision making about treatment tapering and managing flares. Rheumatologists' (n = 12, 5 female) perspectives on tapering bDMARDs and tsDMARDs varied widely, from very supportive to completely opposed, and influenced their views on the DA. Rheumatologists expressed concerns about patient comprehension, destabilizing a stable situation, risks of flare, and extending appointment times. Despite their initial reservations about sending the DA to all eligible patients ahead of appointments, 3 of 4 participating rheumatologists adopted this approach during the pilot, which had the benefit of facilitating patient-led conversations. A DA-led strategy for tapering advanced therapy in RA was acceptable to patients and feasible in practice. Sending patients a DA ahead of their appointment facilitated patient-led conversations about tapering.

Clinical Phenotype of HLA B*44 Patients in a Rheumatology Outpatient Clinic Favors Peripheral Arthropathies.

Objective: The genetic background of HLA-B*27 in spondyloarthritis is known, and the search for another gene with similar role is ongoing. We wanted to investigate clinical presentations of HLA-B*44 patients in rheumatology practice. Methods: A cross-sectional retrospective study of 303 HLA-B*44 adult patients from the outpatient rheumatology clinic from 5/2018-5/2024. Clinical phenotype, confirmed or excluded rheumatic diagnosis, therapy used, and data on HLA A, B, and DR alleles inherited with B*44 were analyzed. Results: A female predominance of 2.79:1 was noted. A total of 150 [49.5%] patients were referred due to peripheral joint pain, 77 [25.4%] due to combined spine and peripheral joint pain or spine alone (57 [18.8%]). A total of 19 [6.3%] patients had no symptoms of the musculoskeletal system. Statistically significant peripheral joint affection was proved in females but not in males (p = 0.04). A total of 121 [40%] patients from B*44 group had established rheumatic disease, with the rest being excluded or under observation. The most common working diagnoses were polyarthritis (32 [10.5%]) and mono-oligoarthritis (14 [4.6%]). A second allele in addition to HLA B*44 showed a similar frequency to the general population. Patients with HLA B*44/44 and B*27/44 genotypes were at the most risk for having definitive rheumatic disease (>60%). Conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs) were used in 38.6% of patients, non-steroidal anti-inflammatory drugs were used in 31.6% of patients, biologic DMARDs were used in 8.9% of patients, and corticosteroids were used in 7.3% of patients. Conclusions: The most common presentation in HLA-B*44 patients is peripheral joint affection. Most patients with HLA-B*27/44 and B*44/44 genotypes had definitive rheumatic disease. B*44 homozygosity or B*27/44 might be risk factors for arthritis development.

Treatment of spondyloarthritis with disease-modifying anti-rheumatic drugs during pregnancy and breastfeeding: comparing the recommendations and guidelines of the principal societies of rheumatology.

This paper aims to provide an overview of the use of treatments available for axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) during pregnancy and breastfeeding, according to current national recommendations and international guidelines, as well as data on the impact on pregnancy outcomes of paternal exposure to treatment. We performed a narrative review of national and international recommendations and guidelines on the reproductive health of patients suffering from rheumatic diseases. The last updated recommendations and guidelines were considered source data. We reported updated information regarding the treatment of axSpA and PsA with nonsteroidal anti-inflammatory drugs, intra-articular glucocorticoids, conventional synthetic disease-modifying antirheumatic drugs (DMARDs), biologic DMARDs, and targeted synthetic DMARDs during the preconception period, pregnancy, and breastfeeding, as well as data related to paternal exposure. We highlighted any medications that should be discontinued and/or not used in the reproductive age group and also treatments that may be continued, avoiding the withdrawal of drugs that can be used in the different phases, thus preventing the risk of increasing disease activity and flares before, during, and after pregnancy in SpA patients. The best management of pregnancy in patients with SpA is based on knowledge of updated drug recommendations, a careful and wise evaluation of the risks/benefits of starting or continuing treatment from the SpA diagnosis in a woman of childbearing age through pregnancy and lactation, and sharing therapeutic choices with other healthcare providers (in particular, gynecologists/obstetricians) and the patient.

The determinants associated with the prescription of a first biologic therapy in patients with axial spondyloarthritis and concomitant fibromyalgia are mostly objective and in line with the recommendations. Results of a cross-sectional survey-based study using a mixed (qualitative and quantitative) approach to help rheumatologists in their daily practice

ObjectivesThere is no consensus on the therapeutic strategy of rheumatologists for patients with spondyloarthritis (SpA) and concomitant fibromyalgia (FM). The main aim of this study was to identify, in a population of rheumatologists practicing in Normandy, France, the determinants associated with their decision to prescribe a first biologic DMARD (bDMARD) in patients with Spa/FM. Specific objectives were to evaluate professional prescribing practices to identify a set of criteria likely to contribute to the therapeutic decision of rheumatologists, and to validate the relevance of these criteria. MethodThis is a cross-sectional survey-based study using a mixed (qualitative and quantitative) method. The quantitative approach was web-based and conducted among rheumatologists in Normandy. ResultsThe qualitative study allowed us to identify a set of criteria likely to contribute to the therapeutic decision of rheumatologists. In the quantitative study, 54/113 rheumatologists filled the questionnaire. Four criteria were considered by all respondents to contribute to their decision to prescribe a first bDMARD: arthritis on physical examination, extra-articular manifestations, systemic inflammation and structural damage on imaging. ConclusionsThe determinants associated with the decision of rheumatologists to prescribe a first bDMARD in patients with SpA/FM were mostly objective, in line with the recommendations in the literature. Most criteria were more related to an approach aimed at ensuring the diagnosis of SpA than evaluating its activity or severity.

Rotation or change of biotherapy after TNF blocker treatment failure for axial spondyloarthritis: the ROC-SpA study, a randomised controlled study protocol

IntroductionAxial spondyloarthritis (axSpA) is a chronic inflammatory disease characterised by inflammatory low back pain. Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended as a first treatment in axSpA. In case of inadequate...

Trends in the use of biologic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis and recently diagnosed colorectal, lung, or prostate cancer.

Biologic disease-modifying antirheumatic drugs (bDMARD) are often discontinued when a patient with rheumatoid arthritis (RA) is diagnosed with cancer. Our aim was to determine trends in bDMARD utilization in patients with RA and recently diagnosed cancer. We examined two national claims databases to identify adults with RA and recently diagnosed colorectal, lung, or prostate cancer (Optum's de-identified Clinformatics® Data Mart Database 2008-2022, and Surveillance, Epidemiology, and End Results Program (SEER) Medicare-linked 2008-2017). We determined time trends in bDMARD and tumor necrosis factor inhibitor (TNFi) prescriptions during the first 3years after cancer with Cochram-Armitage tests and multivariable logistic regression. Cancer cohorts were analyzed separately. We included 3595 patients in all six cohorts (in Clinformatics® 503 with colorectal, 468 with lung, and 440 with prostate cancer; in SEER-Medicare 580 with colorectal, 1010 with lung, and 594 with prostate cancer). No significant increase was observed in bDMARD or TNFi utilization over time. Overall, use of bDMARD within the first 3years of follow-up ranged from 16.7% (Clinformatics® lung cohort) to 29.7% (SEER-Medicare colorectal cohort). The major predictor of bDMARD utilization was prior use in the 3months before cancer diagnosis (p < 0.001 for all cancers) and earlier cancer stage (p < 0.001 in colorectal and lung cancer and p = 0.05 in prostate cancer). Use of bDMARD in patients with RA and recently diagnosed common cancers has not increased since 2008. Additional evidence on the safety of bDMARD in patients with early cancer is needed to ensure appropriate management of their RA. Key Points • Use of bDMARD and TNFi in patients with RA and early colorectal, lung, or prostate cancer has been stable since 2008, with no significant increases over time. • The major determinant of receiving bDMARD after cancer diagnosis was prior treatment with bDMARD in the prior 3months before cancer. • Patients with advanced cancer stage and distant metastases were less likely to receive bDMARD and TNFi than those at early stages of disease.

Interstitial Lung Disease in Patients With Rheumatoid Arthritis or Psoriatic Arthritis Initiating Biologics and Controls: Data From 5 Nordic Registries.

Interstitial lung disease (ILD) is one of the most common pulmonary manifestations of rheumatoid arthritis (RA), but its prevalence has not been investigated in psoriatic arthritis (PsA). The role of methotrexate (MTX) in ILD development remains under debate. This study (1) compares the incidences of ILD in patients with RA or PsA initiating a first biologic disease-modifying antirheumatic drug (bDMARD) to that in the general population, and (2) investigates the role of MTX comedication on ILD incidence. Patients were identified in 5 rheumatology registries. Demographics, MTX use, and disease activity were retrieved. Matched subjects from the general population were available from 4 countries. Incidence of ILD during follow-up of up to 5 years was assessed through national patient registries. Subjects with prior ILD were excluded. Adjusted hazard ratios (HRs) were calculated for ILD incidence in patients vs the general population, and for MTX users vs nonusers. During follow-up of 29,478 patients with RA and 10,919 patients with PsA initiating a first bDMARD and 362,087 population subjects, 225, 23, and 251 cases of ILD were identified, respectively. HRs for ILD (vs population subjects) were 9.7 (95% CI 7.97-11.91) in RA and 4.4 (95% CI 2.83-6.97) in PsA. HRs for ILD with MTX comedication (vs nonuse) were 1.0 (95% CI 0.72-1.25) in RA and 0.9 (95% CI 0.38-2.05) in PsA. Among patients with RA and PsA initiating a bDMARD, the risk of ILD was higher than in the general population, and was highest in RA. MTX comedication was not a risk determinant for ILD.

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.

Increased risk of Pneumocystis jirovecii colonization in rheumatoid arthritis patients on biologics and Janus kinase inhibitor

BackgroundThe prevalence of Pneumocystis jirovecii (PJ) pneumonia among rheumatic patients is rising. PJ colonization serves as a reservoir for transmission and precedes the development of PJ pneumonia. We aim to clarify the association of PJ colonization in patients of rheumatoid arthritis (RA) treated with biologics or Janus kinase inhibitors (JAKi). MethodsA prospective cohort study was performed from March 2021 to July 2022 in the rheumatology outpatient department of National Cheng Kung University Hospital. We obtained oral-wash samples from asymptomatic RA patients treated with biologic disease-modifying antirheumatic drugs (bDMARDs) and JAKi. A real-time quantitative polymerase chain reaction assay focusing on the mitochondrial large subunit ribosomal ribonucleic acid gene of PJ was applied to detect colonization. ResultsOne hundred and ten RA patients were enrolled. Adjusted odds ratios (ORs) of PJ colonization were 6.40 (95% CI 1.34-30.57, p-value =0.02) in patients receiving bDMARDs or JAKi. Specifically, in patients treated with bDMARDs the adjusted OR was 8.08 (95% CI 1.57-41.51, p-value=0.012), and a trend toward developing PJ colonization was further identified in patients receiving JAKi (adjusted OR: 4.79, 95% CI 0.89-25.91, p=0.069). Among patients treated with bDMARDs or JAKi, medication duration >3 years and age >60 y/o are risk factors for PJ colonization. ConclusionRA patients on bDMARDs or JAK inhibitors have an approximately 6-fold higher risk of developing P. jirovecii colonization. Patients treated with bDMARDs had an 8-fold higher risk of P. jirovecii colonization. Risk factors of PJ colonization are medication duration >3 years and age > 60 y/o.

The Retention Rate and Safety of Secukinumab as a First-Line Biologic Agent in Axial Spondyloarthritis Compared to a First Tumor Necrosis Factor (TNF) Inhibitor: A Real-World, Longitudinal Study.

Background and objective Secukinumab (SECU)is a biologic disease-modifying antirheumatic drug (bDMARD)that has demonstrated effectiveness against axial spondyloarthritis (ax-SpA). However, in clinical practice, secukinumab is most commonly used as a second-line treatment after failure of or intolerance to tumor necrosis factorinhibitors (TNFi). In this study, we aimed to compare the two-yeardrug retention between secukinumab and TNFi in biologic-naïve patients with ax-SpA, to estimate the remission/low disease activity (LDA) rates in both groups and assess thesafety profiles. Methods This was a longitudinal observational study involving patients with ax-SpA who were biologic-naïve and were receiving SECU or TNFibetween December 2019 and December 2021. The two-year therapeutic retention rate in both groups was determined. Remission and LDA rates obtained at 24 months according to the Ankylosing Spondylitis Disease ActivityScorebased on C-reactive protein (ASDAS-CRP) scale, as well as the safety profile, were compared between the two groups. Results Seventy-five patients were included in the study. Of them, 34.6% received SECU, while 65.3% received TNFi; 85.3% were males. The mean age was 37.8 ±9 years, the mean disease duration was 10.2 ±6.1 years, and the initial ASDAS-CRP was 3.5 ±0.8. At 24 months; the therapeutic retention rate was 70% for SECU and 66% for TNFi. The reasons for discontinuation were inefficacy (SECU: 11.5%, TNFi: 20.4%, p=0.33), side effects (SECU: 0, TNFi: 4.1%, p=0.29), and socioeconomic conditions (SECU: 15.5%, TNFi: 10.2%, p=0.51). The rate of patients achieving remission and LDA was comparable between the two groups: (remission - SECU: 23.1%, TNFi: 24.5%, p=0.92; LDA - SECU: 73.1%, TNFi: 73.5%, p=0.16). There was no statistically significant difference in the safety profile. Conclusions Our findings suggestthat the effectiveness and safety of secukinumab for ax-SpA in biologic-naïvepatients are comparable to those of TNFi.

SOX-5 Transcription Factor: a Novel Psoriatic Autoantigen Preferentially Found in Women.

Adaptive immunity mediates psoriatic disease pathogenesis. We aimed to identify novel psoriatic autoantigens and their phenotypic associations in deeply characterized patient cohorts. Sera from psoriatic arthritis (PsA) patients were used for autoantibody discovery. Immunoprecipitations performed with cell lysates were on-bead digested, and autoantigens were identified by mass spectrometry. Prevalence and clinical features associated with anti-SRY-Box transcription factor-D (SOX-D) antibodies were determined by screening discovery cohorts of patients with PsA (n = 135), patients with psoriasis without PsA (n = 24), and healthy controls (n = 41). A PsA validation cohort (n = 325) and disease control samples of individuals with rheumatoid arthritis (RA; n = 66) and systemic lupus erythematosus (SLE, n = 66) were assayed for anti-SOX5 antibodies. Disease characteristics were compared by antibody status. Longitudinal data were analyzed using linear mixed-effects models with patient-specific intercept to ascertain associations. We also tested PsA sera for the recently described anti-ADAMTS-L5 autoantibody in PsA. The novel autoantigens identified were SOX-D transcription factors, with SOX-5 being the focus of this analysis. Anti-SOX5 antibodies were present in 8.9% (12 of 135) and 4.3% (14 of 323) of patients in the PsA discovery and validation cohorts, respectively, 12.5% of patients (3 of 24) in the psoriasis group, 2.4% (1 of 41) of healthy controls, and 7.6% (5 of 66) each of patients in the RA and SLE groups. Anti-SOX5 were associated with female sex in both PsA cohorts (discovery: 15.7% women, 2.6% men, P = 0.006; validation: 6.3% women, 1.4% men, P = 0.049). In a longitudinal analysis adjusted for sex, anti-SOX5 associated with biologic disease-modifying antirheumatic drug treatment (95% vs 61%; P = 0.001; n = 96) and with differences in estimated treatment effects by mechanism of action. Anti-ADAMTS-L5 autoantibodies were identified in 8 of 124 patients (6.5%) in the PsA group. SOX-D transcription factors are novel psoriatic autoantigens. Anti-SOX5 antibodies were preferentially found in women with PsA and associated with specific clinical and treatment characteristics, suggesting that anti-SOX5 antibodies may identify mechanistic subgroups. We independently validated anti-ADAMTS-L5 autoantibodies in PsA.

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.

Safety and Efficacy of Bimekizumab in Patients with Psoriatic Arthritis: 2-Year Results from Two Phase 3 Studies.

Psoriatic arthritis (PsA) is a chronic inflammatory disease requiring long-term treatment. Bimekizumab, a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A, has demonstrated tolerability and sustained clinical efficacy for up to 1year for patients with PsA. Here, we report the longer-‍term safety and efficacy of bimekizumab up to 2years. BE OPTIMAL (biologic disease-modifying antirheumatic drug [bDMARD]-naïve) and BE COMPLETE (prior inadequate response/intolerance to tumor necrosis factor inhibitors [TNFi-IR]) assessed subcutaneous bimekizumab 160mg every 4weeks in patients with PsA. BE OPTIMAL included a reference arm (adalimumab 40mg every 2weeks); patients switched to bimekizumab at week 52 with no washout between treatments. BE OPTIMAL week 52 and BE COMPLETE week 16 completers were eligible for the BE VITAL open-label extension. Efficacy outcomes are reported to week 104/100 (BE OPTIMAL/BE COMPLETE). A total of 710/852 (83.3%) bDMARD-naïve and 322/400 (80.5%) TNFi-IR patients completed week 104/100. Up to 104weeks, patients treated with bimekizumab in BE OPTIMAL and BE COMPLETE had treatment-emergent adverse event incidence rates (exposure-adjusted incidence rate/100 patient-years) of 179.9 (95% CI 166.9, 193.7) and 100.3 (89.2, ‍112.4), respectively. The proportion of patients achieving efficacy outcomes (≥ 50% improvement from baseline in American College of Rheumatology [ACR] response criteria, 100% improvement from baseline in Psorisis Area and Severity Index [PASI], minimal disease activity [MDA]) was sustained in all patients from week 52 to week 104/100. Bimekizumab was well tolerated for up to 2years of treatment and no new safety signals were observed. Sustained clinical efficacy was observed up to 2years in bDMARD-naïve and TNFi-IR patients with active PsA. Patients switching from adalimumab to bimekizumab demonstrated further improvement in skin and nail symptoms, and sustained efficacy in joint symptoms. BE OPTIMAL (NCT03895203), BE COMPLETE (NCT03896581), BE VITAL (NCT04009499).

Efficacy and safety of Janus kinase inhibitors in patients with difficult-to-treat rheumatoid arthritis.

This study evaluated the effectiveness of Janus kinase inhibitors (JAKi) in patients with difficult-to-treat rheumatoid arthritis (D2T RA). This study included 220 patients with RA who were treated with JAKi. Sixty-two patients were naïve to biological disease-modifying anti-rheumatic drugs (bDMARDs)/JAKi (1st group), 57 patients were failure to one bDMARDs/JAKi (2nd group), and 101 patients were failure to ≥ 2 bDMARDs/JAKi. Of these 101 patients, 25 did not meet the D2T RA criteria (non-D2T RA group) and 76 met the D2T RA criteria (D2T RA group). : DAS28-ESR was improved in all groups at 24 weeks (1st: p<0.01, 2nd: p<0.01, non-D2T RA: p=0.01, D2TRA: p=0.02), and improvement ratio of DAS28-ESR was not different between DT2RA group and 2nd (p=0.73) or non-D2T RA group (p=0.68). Glucocorticoid use (odds ratios: 8.67; 95% CI: 1.23-60.90; P=0.03) and number of past bDMARD/JAKi uses ≥ 3 (odds ratios: 10.55; 95% CI: 1.39-80.30; P=0.02) were risk factors for DAS28-ESR ≥ 3.2 at 24 weeks in the D2T RA group. Clinical efficacy of JAKi in D2T RA group did not differ from that in 2nd and non-D2T RA groups. Glucocorticoid use and multiple bDMARD/JAKi failure were poor prognostic factors for D2T RA.