Use Of bDMARDs Research Articles

A decade of progress in juvenile idiopathic arthritis treatments and outcomes in Canada: results from ReACCh-Out and the CAPRI registry.

To assess changes in juvenile idiopathic arthritis (JIA) treatments and outcomes in Canada, comparing 2005-2010 and 2017-2021 inception cohorts. Patients enrolled within three months of diagnosis in the Research in Arthritis in Canadian Children Emphasizing Outcomes (ReACCh-Out) and the Canadian Alliance of Pediatric Rheumatology Investigators Registry (CAPRI) cohorts were included. Cumulative incidences of drug starts and outcome attainment within 70 weeks of diagnosis were compared with Kaplan-Meier survival analysis and multivariable Cox regression. The 2005-2010 and 2017-2021 cohorts included 1128 and 721 patients, respectively. JIA category distribution and baseline clinical juvenile idiopathic arthritis disease activity (cJADAS10) scores at enrolment were comparable. By 70 weeks, 6% of patients (95% CI 5, 7) in the 2005-2010 and 26% (23, 30) in the 2017-2021 cohort had started a biologic DMARD (bDMARD), and 43% (40, 47) and 60% (56, 64) had started a conventional DMARD (cDMARD), respectively. Outcome attainment was 64% (61, 67) and 83% (80, 86) for inactive disease (Wallace criteria), 69% (66, 72) and 84% (81, 87) for minimally active disease (cJADAS10 criteria), 57% (54, 61) and 63% (59, 68) for pain control (<1/10), and 52% (47, 56) and 54% (48, 60) for good health-related quality of life (≥9/10). Although baseline disease characteristics were comparable in the 2005-2010 and 2017-2021 cohorts, cDMARD and bDMARD use increased with a concurrent increase in minimally active and inactive disease. Improvements in parent and patient-reported outcomes were smaller than improvements in disease activity.

Adalimumab serum levels and anti-drug antibodies: associations to treatment response and drug survival in inflammatory joint diseases.

To explore associations between serum adalimumab level, treatment response and drug survival in order to identify optimal drug levels for therapeutic drug monitoring of adalimumab. Also, to assess the occurrence and risk factors of anti-drug antibody (ADAb) formation. Non-trough adalimumab and ADAb levels were measured by automated fluorescence assays in serum collected after 3 months of adalimumab treatment in patients with RA, PsA or axial SpA (axSpA) included in the observational NOR-DMARD study. Treatment response was evaluated after 3 months and drug survival was evaluated during long-term follow-up. In 340 patients (97 RA, 69 PsA, 174 axSpA), the median adalimumab level was 7.3 mg/l (interquartile range 4.0-10.3). A total of 33 (10%) patients developed ADAbs. Findings were comparable across diagnoses. In RA and PsA, adalimumab levels ≥6.0 mg/l were associated with treatment response [odds ratio (OR) 2.2 (95% CI 1.0, 4.4)] and improved drug survival [hazard ratio 0.49 (95% CI 0.27, 0.80)]. In axSpA, a therapeutic level could not be identified, but higher adalimumab levels were associated with response. Factors associated with ADAb formation were previous bDMARD use, no methotrexate comedication and the use of adalimumab originator compared with GP2017. Higher adalimumab levels were associated with a better response and improved drug survival for all diagnoses, with a suggested lower threshold of 6.0 mg/l for RA/PsA. This finding, the large variability in drug levels among patients receiving standard adalimumab dose and the high proportion of patients developing ADAbs encourages further investigations into the potential role of therapeutic drug monitoring of adalimumab.

Tofacitinib Efficacy and Safety in Patients With Ankylosing Spondylitis by Prior Biologic Disease-Modifying Antirheumatic Drug Use: A Post Hoc Analysis.

To evaluate the efficacy and safety of tofacitinib in patients with ankylosing spondylitis (AS) by prior biologic disease-modifying antirheumatic drug (bDMARD) use. Data from a placebo-controlled, double-blind study of patients with active AS were analyzed. Patients received tofacitinib 5 mg twice daily (BID) or placebo to week 16; all received open-label tofacitinib 5 mg BID to week 48 and were stratified by prior treatment (bDMARD-naive or tumor necrosis factor inhibitor [TNFi]-inadequate responder [IR], including bDMARD-experienced [non-IR]). Disease activity/safety were assessed throughout. Of 269 patients, 207 (77%) were bDMARD-naive; 62(23%) were in the TNFi-IR subgroup. TNFi-IR patients had higher baseline BMI (28.0 vs. 26.1 kg/m2 ), longer symptom duration (14.4 vs. 13.2 years), and lower concomitant conventional synthetic DMARD use (14.5% vs. 30.9%) than bDMARD-naive patients. At week 16, for most outcomes, tofacitinib efficacy exceeded placebo for both subgroups and was sustained to week 48. At week 16, tofacitinib versus placebo differences were similar between bDMARD-naive and TNFi-IR patients (Assessment in Spondyloarthritis international Society 40 treatment difference [95% confidence interval]: 30.8% [19.1%-42.6%] vs. 19.4% [1.7%-37.0%]). Adverse event (AE) proportions were similar between tofacitinib-treated bDMARD-naive/TNFi-IR patients (77.5%/77.4%) at week 48 with no deaths. A numerically higher proportion of tofacitinib-treated TNFi-IR versus bDMARD-naive patients discontinued study drug (12.9% vs. 3.9%) or dose reduced/temporarily discontinued due to AEs (19.4% vs. 11.8%). Tofacitinib efficacy exceeded placebo at week 16 for bDMARD-naive/TNFi-IR patients and was sustained to week 48. The absolute magnitude of responses was generally greater in bDMARD-naive patients versus TNFi-IR patients. More TNFi-IR versus bDMARD-naive patients discontinued or dose reduced/temporarily discontinued tofacitinib due to AEs. Small sample size and sample size differences between subgroups limited the interpretation.

Factors associated with sarcopenia in Japanese patients with rheumatoid arthritis: results from the IORRA cohort study.

To investigate the prevalence of and factors associated with sarcopenia in Japanese patients with rheumatoid arthritis (RA).We analyzed a cross-section of patients with RA participating in the Institute of Rheumatology Rheumatoid Arthritis cohort survey in 2021. Participants completed self-administered questionnaires, including a 5-item sarcopenia screening index (SARC-F). Patients with a SARC-F score of 4 or higher were categorized as having sarcopenia.Among 2416 Japanese patients with RA (2113 women and 303 men; mean age 63.9years), 341 (14.1%) patients were categorized as having sarcopenia. In a multivariable analysis of patients of all ages, age, body mass index (BMI), disease duration, history of fracture, patient pain on a visual analog scale (VAS), patient or physician global assessments based on VAS, and use of nonsteroidal anti-inflammatory drugs (NSAIDs), biologic disease-modifying antirheumatic drugs (bDMARDs), and corticosteroids were significantly (P < 0.05) associated with sarcopenia. Disease duration, patient global assessments based on VAS, and use of NSAIDs and bDMARDs were significantly associated with sarcopenia among the patients aged < 65years, whereas age, female sex, BMI, disease duration, history of fracture, patient pain VAS and global assessments based on VAS, and use of bDMARDs and corticosteroids were significantly associated with sarcopenia in patients aged ≥ 65years.In Japanese patients with RA, age, BMI, disease duration, history of fracture, patient pain VAS and global assessments based on VAS, and use of NSAIDs, bDMARDs, and corticosteroids were associated with sarcopenia. Among older patients with RA, female sex was additionally associated with sarcopenia. Key Points • To our knowledge, this is the first report showing factors associated with sarcopenia in Japanese patients with rheumatoid arthritis using a large cohort database. • Age, BMI, disease duration, history of fracture, patient pain on a visual analog scale, and use of nonsteroidal anti-inflammatory drugs, biologic disease-modifying antirheumatic drugs, and corticosteroids were associated with sarcopenia in Japanese patients with rheumatoid arthritis. Limited to elderly patients, female sex was also associated with sarcopenia.

Systemic juvenile idiopathic arthritis: The Great Ormond Street Hospital experience (2005-2021).

Systemic juvenile idiopathic arthritis (sJIA) is a complex, systemic inflammatory disorder driven by both innate and adaptive immunity. Improved understanding of sJIA pathophysiology has led to recent therapeutic advances including a growing evidence base for the earlier use of IL-1 or IL-6 blockade as first-line treatment. We conducted a retrospective case notes review of patients diagnosed with sJIA over a 16-year period (October 2005-October 2021) at Great Ormond Street Hospital for Children. We describe the clinical presentation, therapeutic interventions, complications, and remission rates at different timepoints over the disease course. We examined our data, which spanned a period of changing therapeutic landscape, to try and identify potential therapeutic signals in patients who received biologic treatment early in the disease course compared to those who did not. A total of 76-children (female n = 40, 53%) were diagnosed with sJIA, median age 4.5 years (range 0.6-14.1); 36% (27/76) presented with suspected or confirmed macrophage activation syndrome. A biologic disease-modifying anti-rheumatic drug (bDMARD) alone was commenced as first-line treatment in 28% (n = 21/76) of the cohort; however, at last review, 84% (n = 64/76) had received treatment with a bDMARD. Clinically inactive disease (CID) was achieved by 88% (n = 67/76) of the cohort at last review; however, only 32% (24/76) achieved treatment-free CID. At 1-year follow-up, CID was achieved in a significantly greater proportion of children who received treatment with a bDMARD within 3 months of diagnosis compared to those who did not (90% vs. 53%, p = 0.002). Based on an ever-increasing evidence base for the earlier use of bDMARD in sJIA and our experience of the largest UK single-centre case series described to date, we now propose a new therapeutic pathway for children diagnosed with sJIA in the UK based on early use of bDMARDs. Reappraisal of the current National Health Service commissioning pathway for sJIA is now urgently required.

Care pathway analysis and evidence gaps in adult-onset Still's disease: interviews with experts from the UK, France, Italy, and Germany.

Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disease of unknown etiology. Published AOSD data are limited, and clinical guidelines were lacking until recently. Managing AOSD remains largely empirical with uncertainties and high variability about the optimal care pathway. Therefore, we used a qualitative approach to collect clinical judgments from the UK, Italy, France and Germany to inform the development of an agreed care pathway. Our work aimed to decrease the uncertainty associated with clinical practice, inform future research in AOSD, and help identify standardized definitions and outcomes in this population. Semi-structured interviews and thematic analysis were conducted. Eleven clinicians were interviewed between May and July 2022: four were based in Italy, three in the UK, two in France, and two in Germany. In this work, we identified the structure of the typical care pathway for AOSD patients, which can be used to inform future economic models in AOSD. The general structure of the pathway was similar across countries. Non-steroidal anti-inflammatory drugs are prescribed during the diagnostic workup while an additive approach is commonly used in confirmed cases: corticosteroids, conventional synthetic disease-modifying antirheumatic drugs, then biologic disease-modifying antirheumatic drugs (bDMARDs) (dose increased before switching). For severe presentations, more aggressive approaches with higher doses and early use of bDMARDs are used. The main elements of variation among countries and clinicians were the criteria used for diagnosis; order of bDMARDs and preferential treatments for articular and systemic patients; and tests for patient monitoring. There is also a lack of standardized outcome measures making comparisons and evidence synthesis challenging. We identified important evidence gaps for clinical practice, e.g., reliable tests or scores predictive of disease progression and treatment outcome, and recommendations for research, e.g., reporting of compliance rates and use of the Yamaguchi criteria for clinical study inclusion. Consensus is needed around the use of the Systemic score in clinical practice and the clinical utility of this score. A standardized definition of remission is also required in AOSD, and further research should look to identify and validate the specific laboratory markers to be considered when assessing remission.

Comorbid infections in patients with spondyloarthritis: frequency, structure and risk factors

Objective: To investigate the frequency, structure, and risk factors of comorbid infections (CI) in patients with spondyloarthritis (SpA).Material and methods. The study included 332 patients with SpA. Patients were interviewed by the investigating physician, and additional information was obtained from medical records.Results and discussion. Respiratory tract (RT) and ear, nose, and throat (ENT) infections ranked first in the structure of CI. Exacerbation of SpA after CI was found in 42% of patients, and more severe CI against the background of SpA was found in 83 patients. 63 cases of severe CI (SCI) were documented, 63.5% of which were infections of the RT and ENT organs. Predictors for the development of lower RT (LRT) and ENT organ infections were the use of biologic disease-modifying antirheumatic drugs (bDMARDs) in general (odds ratio, OR 2.018; 95% confidence interval, CI 1.221-3.335; p=0.006 and OR 1.761; 95% CI 1.1-2.819, respectively; p=0.018) and tumor necrosis factor-α (TNF-α) inhibitors in particular (OR 2.376; 95% CI 1.417-3.983; p=0.001 and OR 1.833; 95% CI 1.123-2.994; p=0.015), and disease duration of more than 5 years (OR 1.774; 95% CI 1.034—3.042; p=0.037 and OR 2.22; 95% CI 1.378-3.576; p=0.001). The risk of developing LRT infection was higher in the presence of chronic lung disease (OR 3.673; 95% CI 1.602-8.425; p=0.002) and Charlesson Comorbidity Index ≥1 (OR 2.381; 95% CI 1.439-3.94; p=0.001), risk of developing ENT organ infections - with the use of &gt;1 bDMARD (OR 2.4; 95% CI 1.199-4.804; p=0.013) and duration of methotrexate therapy over 5 years (OR 2.478; 95% CI 1.053-5.831; p=0.038). Risk factors for the development of SCI were the use of bDMARDs in general (OR 1.941; 95% CI 1.063-3.545; p=0.031) and TNFα in particular (OR 2.246; 95%, CI 1.218-4.139; p=0.01).Conclusion. The problem of CI in SpA is of great importance. The vast majority of patients with SpA should be vaccinated against pneumococcal infection and influenza.

How has the COVID-19 pandemic affected our rheumatology patients using biological/targeted DMARDs?

We aimed to investigate the effects of the coronavirus disease 2019 (COVID-19) pandemic on the course and treatment of patients with inflammatory rheumatic musculoskeletal disease (iRMD) using biologic or targeted synthetic disease modifying and rheumatic drugs (b/tsDMARDs). The study was carried out in two stages: in the first stage we investigated the delay of b/tsDMARD treatment in the first 3 months of the pandemic; in the second stage, we investigated all patients who decided to continue treatment after interruption in the 12-month period. A total of 521 patients were included in the study. The iRMD diagnosis was listed as spondyloarthritis (SpA) (54.3%), rheumatoid arthritis (RA) (25.7%), psoriatic arthritis (PsA) (8.4%), vasculitis (6.1%), and others (5.4%). Concurrent use of hydroxychloroquine (hazard ratio [HR] = 1.49), iv bDMARD use (HR = 1.34), and a history of discontinuation of drug in the first 3 months of the pandemic (HR = 1.19) were determined as factors that reduced 12-month drug retention rates. The use of glucocorticoid (HR = 3.81) and having a diagnosis of interstitial lung disease/chronic obstructive lung disease (HR = 4.96) were found to increase the risk of being infected by SARS coronavirus 2 (SARS-CoV-2). It was shown that approximately 1/5 of iRMD patients using b/tsDMARDs delayed their treatment due to the fear of COVID-19 in the first three months of the pandemic process. However, with good communication with the patients, b/tsDMARD treatment was restarted and the 12-month drug retention status was quite high.

Inflammation and immunomodulatory therapies influence the relationship between ATP-binding cassette A1 membrane transporter-mediated cholesterol efflux capacity and coronary atherosclerosis in rheumatoid arthritis

ObjectivesHigh-density lipoprotein (HDL) removes cholesterol from cells in atherosclerotic lesions, a function known as cholesterol efflux capacity (CEC). ATP-binding-cassette A1 (ABCA1) membrane transporter starts cholesterol transfer from macrophages to HDL particles. In rheumatoid arthritis (RA), methotrexate and biologic disease modifying drugs (bDMARDs) are atheroprotective whereas corticosteroids and C-reactive protein (CRP) are proatherogenic. We evaluated the influence of these factors on the relationship of ABCA1-CEC with atherosclerosis and cardiovascular events. MethodsAtherosclerosis was evaluated with computed tomography angiography in 140 patients with RA and repeated in 99 after 6.9 ± 0.3 years. Events including acute coronary syndromes, stroke, cardiovascular death, claudication, revascularization, and heart failure were recorded. ABCA1-CEC was quantified in J774A.1 murine macrophages and reported as percentage of effluxed over intracellular cholesterol. ResultsHigher ABCA1-CEC associated with (i) more calcified plaques at baseline only in patients with CRP>7 mg/L (median) (p-interaction = 0.001) and methotrexate nonusers (p-interaction = 0.037), and more partially-calcified plaques only in bDMARD nonusers (p-interaction = 0.029); (ii) fewer new calcified plaques in patients with below-median but not higher time-averaged CRP (p-interaction = 0.028); (iii) fewer new total and calcified plaques in prednisone unexposed but not patients exposed to prednisone during follow-up (p-interaction = 0.034 and 0.004) and (iv) more new plaques in baseline bDMARD nonusers and fewer in bDMARD users (p-interaction ≤ 0.001). Also, ABCA1-CEC associated with greater cardiovascular risk only in baseline prednisone users (p-interaction = 0.027). ConclusionABCA1-CEC associated with decreased atherosclerosis in patients with below-median baseline and time-averaged CRP and bDMARD use. Conversely, ABCA1-CEC associated with increased plaque in those with higher CRP, corticosteroid users, methotrexate nonusers, and bDMARD nonusers. While in well-treated and controlled disease ABCA1-CEC appears atheroprotective, in uncontrolled RA its action may be masked or fail to counteract the inflammation-driven proatherogenic state.

Switching biological disease-modifying antirheumatic drugs and Janus kinase inhibitors in patients with rheumatoid arthritis

The goal of treatment of rheumatoid arthritis (RA) is to achieve remission or low disease activity. A wide range of disease-modifying antirheumatic drugs is used for the treatment of RA, including biological disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (JAKi). However, even with the use of bDMARDs and JAKi, this goal can be achieved only in 40–60% of patients. Insufficient response to bDMARs and JAKi is the reason for switching to other drugs from the same group, such as tumor necrosis factor-α inhibitors, and to drugs with a different mechanism of action. The need to change therapy may be associated with its ineffectiveness due to various immune, genetic and epigenetic mechanisms, with the development of adverse reactions, as well as with comorbid pathology. To date, there is no certain predictors of effectiveness of a particular bDMARDs and JAKi and of the need and strategy for changing the therapy.The review considers the effectiveness of various classes of bDMARDs and JAKi in RA, the frequency and risk factors associated with the need to switch patients to other drugs, the role of chemokines as promising markers of response to RA treatment.

Clinical features of patients with ankylosing spondylitis with inefficacy of two or more biological disease modifying antirheumatic drugs

The “Treat-to-target” (T2T) strategy for axial spondyloarthritis (axSpA) has made it possible to optimize therapy in most patients, but in some of them the treatment goals are not achieved.Objective: to analyze the clinical features of patients with ankylosing spondylitis (AS) with inefficacy of two or more biological disease modifying antirheumatic drugs (bDMARDs).Material and methods. From February 2020 to March 2022 458 patients with AS, who met the modified New York criteria of 1984, were admitted to V.A. Nasonova Research Institute of Rheumatology. From this group, 30 (6.6%) patients with high clinical disease activity and inefficacy of at least two bDMARDs were selected. The control group consisted of 139 (30.5%) patients with AS, who either had no history of bDMARDs use, or had previously received only one of them. All patients were examined in accordance with generally accepted methods and underwent a double expert control.Results and discussion. Men predominated in the main and control groups (67 and 60%, respectively). In patients of the main group, there was a higher laboratory activity of the disease, especially ESR (p=0.002), more often peripheral arthritis was detected. In both groups, there was a high incidence of coxitis (69.2 and 69.7%, respectively), while in the main group there were significantly more patients who underwent total joint arthroplasty, and the frequency of detected syndesmophytes was 2 times lower compared to the control. Differences in the features of AS onset were also established: in the main group, the disease often began with reactive arthritis (ReA), while in the control group, with inflammatory back pain.Conclusion. The T2T strategy in axSpA does not always lead to the achievement of the intended goals, and, according to our data, among inpatients with AS, the number of people with a history of inefficacy of two or more bDMARDs reaches 6%. In these patients, compared with the control, the following features of the disease can be distinguished: frequent onset with ReA, a significant incidence of peripheral arthritis and joint arthroplasty, and a higher ESR.

Chinese Registry of Psoriatic Arthritis (CREPAR): I. Clinical characteristics of Chinese patients with psoriatic arthritis.

To describe the clinical characteristics of Chinese patients with psoriatic arthritis (PsA) using the data recorded in the Chinese Registry of Psoriatic Arthritis (CREPAR). This is a cross-sectional study based on the CREPAR registry, which is a prospective registry founded in December 2018. Data regarding clinical characteristics and treatment of patients were collected during every visit. Data recorded at enrollment were extracted, analyzed, and compared with data in other registries or cohorts. A total of 1074 patients were registered from December 2018 to June 2021. Of these, 929 (86.5%) patients had a history of peripheral arthritis, and 844 patients (78.6%) had peripheral arthritis at enrollment, of which polyarthritis is the most common subtype. Axial involvement was present in 39.9% of patients, and 50 (4.7%) patients had axial involvement only. More than half of the patients (55.4%) had at least two musculoskeletal presentations at enrollment. The prevalence of low disease activity and remission according to DAPSA were 26.4% and 6.8%, respectively. Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biological DMARDs were used in 64.9% and 29.1% of patients, respectively. Among patients with different musculoskeletal presentations, patients with dactylitis had the highest proportion of nonsteroidal anti-inflammatory and csDMARD use. The proportion of patients receiving bDMARDs was highest in axial PsA. The CREPAR registry has provided information on Chinese patients with PsA. Compared with data in other registries or cohorts, the disease activity of patients in CREPAR was higher, and the proportion of bDMARD use was lower.

Vaccination of pneumococcal infection in patients with systemic lupus erythe matosus and antiphospholipid syndrome: experience of 6 years of use

Infections remain one of the main causes of morbidity and mortality in patients with immuno-inflammatory rheumatic diseases. Objective – to study the efficacy, immunogenicity and safety of the 23-valent polysaccharide pneumococcal vaccine (PPV-23) in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (AРS). Materials and methods. 91 patients were included in the study: 78 with SLE, of which 18 (23 %) – with secondary AРS, 13 – with primary AРS. 85 patients received immunosuppressive therapy, including 30 – genetically engineered biological drugs (bDMARD); 23 – anticoagulants. PPV-23 was administered subcutaneously, patients were observed for a year after vaccination. Results. Local reactions were observed in 49% of patients with SLE and secondary AРS, in 23% of patients with primary AРS. General reactions were noted in isolated cases, were short-term and did not require additional prescriptions. During the follow-up period, no exacerbations of SLE, relapses of thrombosis and thromboembolism associated with vaccination were detected; no development of new autoimmune diseases was registered. 10 (13%) patients with SLE were immunized against the background of high activity of the disease, no adverse reactions were recorded. In some patients, a transient increase in a-DNA and ANF was observed during the year without signs of exacerbation of the disease. 56% of patients with SLE and secondary AРS, 15.4% with primary AРS were “responders” to the vaccine. There was no negative effect on the immune response of the dose of GC &gt;10 mg/day, age, duration and activity of the disease. With the treatment of bDMARD, a full-fledged vaccine response was recorded much less frequently than with standard therapy (38% and 67.4%, respectively; p=0.01). After vaccination, there was a significant decrease in the number of lower respiratory tract infections (LRTI) (p=0.0001), including community-acquired pneumonia (PN) (p=0.03) and acute bronchitis (p=0.04), ENT infections (p=0.001). In the treatment of rituximab (RTM), compared with belimumab (BLM), a greater number of LRTI was observed, mainly due to PN. After vaccination on RTM therapy, the number of INDP in general (p=0.008) and PN in particular (p=0.03) decreased, isolated cases of LRTI and ENT organs were recorded on BLM therapy. Within 4–6 years after vaccination, 30 patients with SLE retained the clinical effect of vaccination, while immunogenicity decreased to 18%. Conclusion. Safety, sufficient immunogenicity, and clinical efficacy of PPV-23 in patients with SLE and AРS have been shown. The use of bDMARD reduces the vaccine response. Immunization performed prior to or during treatment with bDMARD lasting &lt;1 year increases the number of vaccine responders.

Biologics Initiation in Rheumatoid Arthritis by Race and Ethnicity: Results From a Randomized Survey Study.

To investigate whether the race and ethnicity of a patient with rheumatoid arthritis (RA) influences rheumatologists' likelihood of choosing to initiate biologic disease-modifying antirheumatic drug (bDMARD) treatment. We conducted a randomized survey experiment in which identical brief case vignettes of hypothetical patients with RA were sent to US rheumatologists (respondents). Three of the four cases included some level of treatment decision ambiguity whereas the fourth case strongly favored bDMARD initiation. Each respondent was shown the four case vignettes, with the race and ethnicity (Black, Hispanic, White) randomly assigned for each case. Each vignette offered multiple choices for next therapeutic step, which we summarized using frequencies and proportions by race and ethnicity version. Among 159 US rheumatologists, we found that for the three cases with some level of treatment decision ambiguity, there was little to no variability in the proportions of respondents who chose to start a biologic for the Black and Hispanic variants (cases 1, 2, and 3). For case 4, respondents generally agreed to start a biologic with some minimal variability across the variants (92.6% for the Black version, 98.1% for the Hispanic version, and 96.2% for the White version). There are conflicting data regarding bDMARD use and initiation in patients with RA based on the sex and race of the patient. This work adds to this conversation by examining how the next therapeutic step chosen by rheumatologists varied by the race and ethnicity of the hypothetical patient.

Intra-articular injections of biological disease-modifying anti-rheumatic drugs in inflammatory arthropathies: An up-to-date narrative review

IntroductionSince the 1990s thebiological disease-modifying anti-rheumatic drugs (bDMARDs) have revolutionized the treatment of chronic dysimmune inflammatory arthropathies such as Rheumatoid Arthritis, Psoriatic Arthritis and Axial Spondylarthritis. Nevertheless, despite a full treatment regimen, mono- and oligoarticular persistence of the synovitis is sometimes observed. The intra-articular (IA) use of bDMARD drugs could resolve the persistent joint inflammation and result in a reduction in the degree of immunosuppression of individuals; moreover, the use of these drugs intra-articularly could be associated with a reduction in the treatment-related costs. MethodsWe extensively searched via PubMed and Google Scholar articles using as keywords “etanercept”, “infliximab”, “adalimumab”, “certolizumab”, “golimumab”, “tocilizumab”, “ixekizumab”, “secukinumab”, “rituximab” each combined with “intra-articular injection”. ResultsWe found and evaluated 161 papers, and then we selected 24 that were highly related to the topic of the present work. The articles examined a total of 349 patients, 85 males (M), and 168 females (F), mean age of 44.75±12.09 years old and considered 556 treated joints. Three hundred and forty-one patients were affected by Rheumatoid Arthritis, 198 by Psoriatic Arthritis, 56 by Axial Spondylarthritis, 26 by Juvenile Idiopathic Arthritis, 19 by Undifferentiated Arthritis, 1 by arthritis associated with inflammatory bowel disease and 9 patients by an unspecified inflammatory articular disorder. All patients were treated intra-articularly with a TNFα inhibitor among Adalimumab, Etanercept or Infliximab. Side effects were documented in 9 out of 349 (2.57%) treated patients and all were mild or moderate. In some cases the effectiveness of IA bDMARDs treatment was maintained for several months, however in the few published randomized controlled trials(RCTs) the corticosteroids (GCs) appeared to act better when administered intra-articularly compared to bDMARDs. ConclusionsThe IA use of bDMARDs seems to be weakly effective in the management of resistant synovitis and not superior to GCs injections. The treatment's main limit appears to be the poor persistence of the compound in the joint.

HPR144 Coverage of Biologics for Rheumatoid Arthritis in Canada

In Canada, there is a need for consistent access to medications across the country to ensure health care equity and the optimal management of patients. In 2015, private drug plans implemented a national standard for coverage of biologic disease-modifying antirheumatic drugs (bDMARDs) in rheumatoid arthritis (RA), which includes a prior trial of dual conventional synthetic DMARDs (csDMARDs). The aims of this study were to acquire an understanding of current bDMARD listing status and coverage criteria across jurisdictions, review the clinical evidence and guideline recommendations regarding the use of csDMARDs and bDMARDs, determine the current utilization of csDMARDs and bDMARDs across jurisdictions, and estimate the budgetary impact if jurisdictions harmonized the time to bDMARD initiation in RA.

CHANGE IN ARTERIAL STIFFNESS AND AMBULATORY BLOOD PRESSURE IN PATIENTS WITH RHEUMATOID ARTHRITIS: THE JOINTHEART STUDY

Objective: Use of disease modifying antirheumatic drugs (DMARDs) has been associated with reduction in blood pressure (BP) and arterial stiffness in clinical trials, but real-word data is lacking. We investigated change in ambulatory BP and arterial stiffness in outpatients with rheumatoid arthritis (RA) eligible for initiation or change in targeted synthetic (ts) or biological (b) DMARDs. Design and method: Eighty-nine consecutive RA patients (age 53±13, 68% women) were examined at initiation of ts/bDMARDs and repeated after 22 months. Ambulatory BP, carotid-femoral-pulse wave velocity (cfPWV) and Disease Activity Score in 28 joints using C-reactive protein (DAS28) were measured at baseline and at follow-up. High cfPWV was defined as cfPWV &gt; 10 m/s in accordance with guidelines. Results: At follow-up, 20% used tsDMARDs, 57% bDMARDs and 67% had achieved remission or low disease activity. DAS28 decreased from 3.9±1.3 at baseline to 2.8±1.2 at follow-up (p&lt;0.001). The ambulatory systolic BP increased (116±11 mmHg vs 120±13 mmHg, p = 0.010), while the ambulatory diastolic BP decreased (76±7 mmHg vs. 73±8 mmHg, p = 0.001) from baseline to follow-up. Body mass index (BMI) increased from 26.5±5.2 kg/m2 to 27.1±4.9 kg/m2, p = 0.009. Changes in ambulatory systolic and diastolic BP were associated with presence of diabetes at baseline, but not DAS28 or use of ts or bDMARDs. Mean cfPWV increased from 7.8±1.6 m/s at baseline to 8.5±1.8 m/s at follow-up (p&lt;0.001). The prevalence of high cfPWV increased from 10.8% to 16.3 %, p = 0.03. DAS28 (beta = 0.32, p = 0.01) and diabetes at baseline (beta = 0.39, p = 0.001) were associated with increase in cfPWV, independent of achieved remission/low disease activity at follow-up, baseline systolic BP, BMI, age, sex and use of antihypertensive drugs. Conclusions: In outpatients with RA, higher disease activity at baseline was associated with an increase in arterial stiffness during follow-up, despite DMARD therapy and significant decrease in disease activity.

Biological Therapies in Inflammatory Myopathies.

Idiopathic inflammatory myopathies (IIM) are a rare group of disorders that feature progressive immune-mediated skeletal muscle destruction along with skin, lung, and joint involvement. Management of IIMs necessitates glucocorticoid therapy followed by conventional steroid-sparing agents to control disease activity. In the settings of refractory myositis or life-threatening manifestations, e.g. lung involvement or oropharyngeal dysphagia, second-line therapies are needed to minimize disease burden, avoid end-organ damage and steroid toxicity, and decrease mortality. These therapies may include biological disease-modifying antirheumatic drugs (bDMARDs), and to a lesser extent, targeted synthetic disease-modifying antirheumatic drugs (TSD). This article reviews the current use of bDMARDs, e.g. intravenous immunoglobulin and rituximab, and a TSD-Janus kinase inhibitors (JAKI)-along with their indications, efficacy, and safety in managing IIM.

E092 Confirmatory factor analyses of the Tampa Scale of Kinesiophobia 11-item version and Pain Catastrophising Scale: A cross-sectional study in people living with axial spondyloarthritis

Abstract Background/Aims The Fear Avoidance Model (FAM) proposes pain-related fear of movement and pain catastrophising to be prominent psychological experiences that compromise physical function and activity behaviour in people living with chronic pain. Yet, little research has tested the FAM in people living with axial spondyloarthritis (axSpA) despite the evidenced benefits of physical activity and exercise. This study examines the structural aspect of construct validity of the 11-item Tampa Scale of Kinesiophobia (TSK-11) and Pain Catastrophising Sale (PCS) as an important first step, to establish valid measurement tools to effectively test the relevance of the FAM for people with axSpA. Methods An online survey was distributed via the National Axial Spondyloarthritis Society including the TSK-11 and PCS. Ninety-eight people with axSpA (M Age = 45.62 SD = 12.16, M BASFI = 3.7 SD = 2.60, Female = 70%, NSAID use = 58.76%, bDMARDS use = 62.24%) completed the survey (December 2020- April 2021). Internal consistency was examined via Cronbach alpha values and confirmatory factor analysis tested the TSK-11's two-factor structure and PCS's three-factor structure. A model has excellent fit to the data with values &amp;lt; 3 for the CMIN/DF, and around .95 for CFI, .06 for RMSEA, .08 for SRMR. Factor loadings &amp;lt; .40 support deletion. Results Alpha values supported the internal consistency of participant responses to the somatic (.78), avoidance behaviour (.80) and overall fear of movement (.89) TSK-11 items. Fit indices also showed a good fit to the data for the TSK-11’s two-factor structure once two error terms were correlated (CMIN/DF = 1.77/42, CFI = .93, RMSEA = .09 (.05 - .12), SRMR= .06). Standardised factors loadings for the somatic and avoidance factors ranged from .43 - .80 and .60 - .72, respectively. Internal consistency for the responses to the PCS-Helplessness (.92), PCS-Magnification (.82), PCS-Rumination (.94) and overall pain catastrophising (.95) scales were also supported. A good fit to the data was shown for the three-factor structure of the PCS (CMIN/DF = 2.15/61, CFI = .94, RMSEA= .11 (.08-.14), SRMR = .04) when two errors were correlated. Standardised factors loadings ranged from .67-.90, (Helplessness), .89 - .92 (Rumination) and .73 - .85 (Magnification). Conclusion The TSK-11 and PCS can be used to measure axSpA patient’s pain related fear of movement and pain catastrophising, but data support continued examination of their construct validity in larger samples of axSpA patients. One TSK-11 item revealed a border line factor loading (.43) for the somatic factor (“pain lets me know when to stop exercising so that I don’t injure myself”). Psychometrically valid instruments will help examine the role of pain related fear of movement and pain catastrophising on important health related outcomes for axSpA patients including physical function and physical activity behaviour. Disclosure P.C. Rouse: Grants/research support; PhD studentship matched funded by Bath Institute for Rheumatic Diseases (RAG-PR-33-120318). T.A. Ingram: None. M. Standage: None. R. Sengupta: Honoraria; Received honoraria for giving talks from Abbyie, Biogen, UCB, Novartis and Pfizer. Grants/research support; Research grants have been received from UCB, Abbvie, and Novartis.

P057 Immunosuppression doubles the risk of COVID-19 infection in a large vaccinated cohort of 898 patients with rheumatic diseases: implications for future practice

Abstract Background/Aims It is recognised that immunosuppressive medications, often relied upon in the management of autoimmune rheumatic disease, inhibit vaccine-induced immunity against the SARS-CoV-2 virus. A key challenge for rheumatologists is maximising immunity provided by the vaccine in their patients. Recent data has implicated methotrexate (MXT), a commonly used disease modifying anti-rheumatic drug (DMARD), in reducing patients’ vaccine-induced immunity against the virus and studies have demonstrated the effectiveness of pausing MXT medication for 2-weeks after receiving the vaccine in boosting patients’ immunity. There is a lack of data exploring the impact of concurrent biologic-DMARD (b-DMARD) use with MXT on COVID-19 infection rates in vaccinated individuals. This analysis forms part of a larger programme of research (clinicaltrials.gov NCT04542031) exploring COVID-19 in patients with rheumatic disease. Here we provide a comparative analysis of COVID-19 infection rates between patients taking MXT either with or without b-DMARD therapy and those on no immunosuppression. Methods We distributed two web-based questionnaires via SMS-messaging in April 2020 and December 2021 and two interim monitoring questionnaires in December 2020 and June 2021. All rheumatology patients with a valid mobile telephone number under follow up at the Royal Wolverhampton Trust were invited to participate in the study; those that consented received follow up questionnaires. We collected information on demographics, rheumatology diagnosis and treatment, vaccination status, and COVID-19 infection rates. Data were collected 7-days following questionnaire distribution. Results Initial questionnaires were sent to 7911 active follow up patients, 1636/7911 (21%) responded and consented to further follow up; 906/1636 (55.4%) provided a complete response to the final survey which was subsequently linked to survey one enabling analysis. Responders were female (622/906, 68.7%), white (865, 95.5%), 60 years or above (519, 57.3%), and vaccinated (898/906; 99.1%). Of those vaccinated significantly more patients that were on any immunosuppressive therapy compared to those on no immunosuppression (92/530 (17.4%) vs. 26/368 (7.1%); p &amp;lt; 0.001), and more in the MXT monotherapy group compared to no immunosuppression (33/222 (14.9%) vs. 26/368 (7.1%); p = 0.001) contracted COVID-19. Similar numbers in the MTX and b-DMARD and b-DMARD without MXT groups (23/140 (16.4%) vs. 36/168 (21.4%); p = 0.23) contracted COVID-19. Conclusion Recent trial data from the VROOM study has demonstrated that omitting a patients MXT therapy for a 2-week period following administration of the COVID-19 vaccine doubles their antibody response. This data highlights that the risk of COVID-19 infection in vaccinated rheumatology patients is doubled in patients on any immunosuppressive medication compared to those on no immunosuppression, while there is no significant difference in infection rates between patients on MXT and a b-DMARD and b-DMARD therapy without MXT. Further work exploring the impact of different types of immunosuppression on COVID-19 vaccine-induced immunity and simple interventions to maximise this immunity in immunosuppressed individuals is required. Disclosure N. Cox: None. J. Bateman: None.