Biologic Disease-modifying Antirheumatic Drugs Research Articles

Disease modification in axial spondyloarthritis - still a controversy?

This review evaluates recent advancements in disease-modifying therapies for axial spondyloarthritis (axSpA). A recent study could not demonstrate an additional effect of NSAID therapy on golimumab [Tumor Necrosis Factor-α inhibitor (TNFi)] on structural progression; however, this might be due to the fact that the study was underpowered. While DMARDs have shown promise in suppressing inflammation, their impact on structural progression remains uncertain. A well powered trial showed no difference in spinal progression between secukinumab [Interleukin17A inhibitor (IL17Ai)] and adalimumab-biosimilar (TNFi). Preliminary data on Janus kinase inhibitors (JAKi) focus on MRI findings but lack evidence on radiographic spinal progression. While some studies suggest promising outcomes, others reveal limitations and inconclusive findings. Recent studies explore the effectiveness of NSAIDs, biological disease-modifying antirheumatic drugs like TNFi and IL-17i, as well as JAK inhibitors in axSpA. Conflicting evidence surrounds these therapies' ability to impede structural progression, with challenges in study design and interpretation. Moreover, changes in demographics and treatment methods underscore the importance of examining trends over time when assessing disease outcomes. Ultimately, ongoing research could benefit from new imaging tools when evaluating therapeutic strategies for modifying disease progression in axSpA.

Higher infection risk for JAK inhibitors tofacitinib and baricitinib compared to subcutaneous biological DMARDs.

Rheumatoid arthritis (RA) is usually treated with disease modifying antirheumatic drugs (DMARDs), including biological DMARDs (bDMARDs) and more recently, Janus kinase inhibitors (JAKi). Randomized trials suggest similar infection risks for JAKi and bDMARDs, but real-world data are scarce. From a nationally representative prescription database, adult RA patients starting a new JAKi or bDMARD between August 1st, 2018, and January 31st, 2021, were included. Prescriptions of antibiotic, antiviral or antifungal medication were used as proxy for infections. Infection incidence rates (IR) were compared between JAKi and bDMARDs and infection risks were estimated using multilevel Poisson regression adjusted for follow-up time and potential confounders and stratified for age < 65 and ≥ 65 years. In 14,989 patients, we identified 20,050 treatment episodes with either JAKi or bDMARDs. The infection IR was significantly higher in JAKi (48/100 patient years) compared bDMARDs (35/100 patient years, adjusted incidence rate ratio (IRR) 1.22, 95% CI 1.12-1.33). More herpes zoster infections were seen in JAKi compared to bDMARDs (adjusted IRR 2.65, 95% CI 1.94-3.60). No significant differences in infection IRs were found comparing JAKi baricitinib and tofacitinib. In older patients, infection IRs were higher, but IRRs were similar between age groups. In comparison to bDMARDs, JAKi are associated with a slightly higher infection risk and a higher risk of herpes zoster specifically. In older patients, infection IRs are higher but similar infection risks for JAKi and bDMARDs are observed. No differences in infection risk between tofacitinib and baricitinib were found. Key Points • Compared to bDMARDs, JAKi are associated with a slightly higher infection risk for all ages • An increased risk of herpes zoster in patients who use JAK inhibitors was confirmed • No significant differences in infection incidence were found between tofacitinib and baricitinib.

Adult-onset Still’s disease: analysis of a monocentric cohort of patients

Objective Adult-onset Still’s disease (AOSD) is a multigenic autoinflammatory disease with a severe systemic involvement. Because of the rarity of the disease, most published cohorts are multicentric. The aim of this report is to describe a monocentric cohort of AOSD patients, reporting clinical features and response to therapy in a long follow-up. Method Thirty-eight patients, attending the Clinical Immunology Unit and fulfilling Yamaguchi, Fautrel, or Daghor-Abbaci classification criteria for AOSD, were recruited for this study. In all patients, clinical and serological data were collected at diagnosis and every 6 months thereafter. The Pouchot score was calculated at every visit. Results Fever, arthromyalgia, and skin rash were the most frequent manifestations, followed by lymphadenopathy, sore throat, arthritis, splenomegaly, hepatic involvement, pleuropericarditis, and weight loss. As far as the disease course is concerned, 25% presented a monocyclic and 35% a polycyclic pattern, and 40% developed chronic articular involvement. Severe complications were observed at disease onset in 21% of the patients. All of the patients were treated with steroids; 74% also received conventional synthetic disease-modifying anti-rheumatic drugs (methotrexate in most cases) and 71% biological disease-modifying anti-rheumatic drugs (interleukin-1 inhibitors in most cases). Therapeutic switching for lack/loss of efficacy or adverse drug reactions was necessary in 66%. Conclusion The analysis of this cohort confirms that AOSD is a complex, severe, and heterogeneous disease. However, despite long-term treatment and comorbidities, therapies are effective and well tolerated. The therapeutic armamentarium now available allows long-lasting remission with low immunosuppression to be achieved in most patients.

Bimekizumab: A Review in Psoriatic Arthritis.

Although several biological disease-modifying antirheumatic drugs (bDMARDs), including interleukin (IL)-17A inhibitors, are approved for psoriatic arthritis, the treatment of this disease remains suboptimal. Bimekizumab (Bimzelx®), a dual IL-17A and IL-17F inhibitor, is approved in the EU, Great Britain and Japan for the treatment of psoriatic arthritis. In pivotal phase 3 clinical trials in patients who were bDMARD-naïve or previously had an inadequate response or intolerance to tumour necrosis factor (TNF) α inhibitors, bimekizumab improved the signs and symptoms of psoriatic arthritis across a range of joint, skin, radiographic and patient-reported outcomes compared with placebo, including the proportion of patients achieving a ≥ 50% response in the American College of Rheumatology criteria. Phase 2 clinical trial data have shown that responses are maintained up to 3 years. Bimekizumab was generally well tolerated in patients with psoriatic arthritis, with a safety profile consistent with that in other approved indications. The most common adverse events included nasopharyngitis, upper respiratory tract infection, oral candidiasis, headache and diarrhoea. In conclusion, bimekizumab extends the treatment options available to patients with psoriatic arthritis.

Relapses of juvenile idiopathic arthritis in adulthood: A monocentric experience.

Our aim was to describe a monocentric cohort of young adult patients with juvenile idiopathic arthritis (JIA), assessing the risk of relapse after transition to adult care. We conducted a retrospective study and collected clinical, serological, and demographic data of young adult patients (18-30 years old) referred to the Transition Clinic of a single Italian centre between January 2020 and March 2023. Patients with systemic-onset JIA were excluded. Primary outcome was disease relapse, defined by Wallace criteria. Risk factors were analysed by Cox proportional hazards regression. Fifty patients with age 18-30 years old were enrolled in the study and followed for a median 30 months. The median disease duration at transition was 15 years. Twenty (40%) patients were on conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and 38 (76%) were on biological DMARDs through adulthood. Twenty-three patients relapsed after transitioning to adult care for a median 9-month follow-up (IQR 0-46.5). Most relapses involved the knees (69.6%). The univariate analysis identified monoarthritis (HR 4.67, CI 1.069-20.41, p value = 0.041) as the main risk factor for relapse within the first 36 months of follow-up. Early onset, ANA positivity, past and ongoing treatment with csDMARDs or bDMARDs, therapeutic withdrawal, and disease activity within 12 months before transition did not significantly influence the risk of relapse. In JIA patients, the risk of relapse after transitioning to adult care remains high, irrespective of disease subtype and treatment. The main risk factor for the early occurrence of articular activity is monoarticular involvement.

Nurses' roles, interventions, and implications for management of rheumatic diseases.

Nurses have become integral members of multidisciplinary teams in managing rheumatic diseases, departing from their traditional patient care roles. This article provides a comprehensive review of nurses' roles, interventions, and impacts in several rheumatic diseases, including rheumatoid arthritis, osteoarthritis, spondyloarthritis, gout, systemic lupus erythematosus, and polymyalgia rheumatica. It has been demonstrated that care under nursing supervision is effective and safe, with benefits including disease management, quality of life, and treatment adherence. In addition, nurses play a crucial role in promoting health, educating patients, and administering biological disease-modifying anti-rheumatic drugs. The COVID-19 pandemic has highlighted the significance of telehealth services and nurses' role in delivering remote care. However, nursing education and training challenges persist, particularly in standardization and access to postgraduate education. Efforts to enhance the role of nurses in rheumatology care are necessary to optimize patient outcomes and meet the evolving needs of individuals with rheumatic diseases. Collaboration across healthcare institutions, professional groups, and educational facilities is necessary for promoting the continual growth and advancement of rheumatology nurse practice. By equipping nurses with the requisite knowledge, expertise, and resources to deliver top-notch care, we can enhance the well-being of individuals with rheumatic diseases and foster improved overall health outcomes.

Sex-related differences in dispensation of rheumatic medications in older patients with inflammatory arthritis: A population-based study.

The aim of our study was to compare dispensation of rheumatic medications between older male and female patients with early rheumatoid arthritis (RA) and psoriatic arthritis (PsA). This retrospective cohort study was performed using health administrative data from Ontario, Canada (years 2010 - 2017) on incident patients with RA and PsA, who were 66 years or older at the time of diagnosis. Yearly dispensation of rheumatic drugs was compared between older male and female patients for three years after diagnosis using multivariable regression models, after adjusting for confounders. The groups of drugs included in the analysis were DMARDs classified as conventional DMARDs (csDMARDs) and advanced therapy (biologic DMARDs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs)), NSAIDs, opioids and oral corticosteroids. Results were reported as Odds Ratios with 95% Confidence Intervals (CI). We analyzed 13,613 patients (64% females) with RA and 1,116 patients (57% females) with PsA. Female RA patients were more likely to receive opioids (OR [95% CI] 1.39 [1.22-1.58] to 1.51 [1.32-1.72]) and NSAIDs (OR [95% CI] 1.14 (1.04-1.25) to 1.16 [1.04-1.30]). Dispensation of DMARDs showed no sex-difference in either group. Subgroup analyses showed more intense use of advanced therapy in the RA cohort and of csDMARDs in the PsA cohort when patient and physician sex was concordant. This study did not identify any sex difference in use of DMARDs among older RA and PsA patients. Reasons for the higher use of opioids and NSAIDs among female RA patients warrants further research.

2023 Management Recommendations of Bangladesh Rheumatology Society on Pharmacological Treatment of Rheumatoid Arthritis With Synthetic and Biologic Disease-Modifying Drugs.

Rheumatoid arthritis (RA) is the most common inflammatory polyarthritis in Bangladesh. Bangladesh Rheumatology Society (BRS) proposes these management recommendations to treat the considerable burden of RA in the resource-constrained situation based on the best current evidence combined with societal challenges and opportunities.BRS formed a task force (TF) comprising four rheumatologists. The TF searched for all available literature, including updated American College of Rheumatology (ACR), European Alliance of Associations for Rheumatology (EULAR), and Asia-Pacific League of Associations for Rheumatology (APLAR) and several other guidelines, and systematic literature reviews until October 2023, and then a steering committee was formed, which included rheumatologists and internists. We followed the EULAR standard operating procedures to categorize levels of evidence and grading of recommendations. This recommendation has two parts -- general (diagnosis of RA, nomenclature of disease-modifying anti-rheumatic drugs [DMARDs], disease activity indices) and management portion. The TF agreed on four overarching principles and 12 recommendations. Overarching principles deal with early diagnosis and disease activity monitoring. Recommendations 1-5 discuss using glucocorticoids, NSAIDs, and conventional synthetic DMARDs (csDMARD). Recommendations 6-9 stretch the use of targeted synthetic DMARDs (tsDMARDs) and biological DMARDs (bDMARDs). The suggested DMARD therapy includes initiation with methotrexate (MTX) or another csDMARD (in case of contraindication to MTX) in the first phase and the addition of a tsDMARD in the second phase, switching to an alternative tsDMARDs or bDMARDs in the subsequent phases. The TF included the Padua prediction score for the thromboembolism risk estimation. Recommendations 10-12 cover infection screening, vaccination, and DMARD tapering. Bangladesh has a higher prevalence of RA. This recommendation will serve as a tool to treat this high burden of patients with RA scientifically and more effectively.

Total knee and hip replacement in rheumatoid arthritis: А current trend

Total joint replacement (TJR) is a surgical procedure widely used in severe destructive joint damage. TJR of the knee and hip joint (TKR and THR respectively) occupies an important place in the complex treatment of rheumatoid arthritis (RA) and osteoarthritis (OA), and can significantly reduce pain and improve function in patients with severe structural joint damage due to an ineffectiveness of conservative therapy. In recent years, due to the development of the modern concept of active treatment of RA (treat-to-target) and the introduction of new classes of anti-inflammatory drugs, such as biologic disease modifying antirheumatic drugs and JAK inhibitors, the need for TJR in RA has begun to decrease. At the same time, the aging of the population, the increase in the number of patients with OA and the lack of generally approved pathogenetic therapy determine the increase of TKR/THR incidence in this disease. This review presents the long-term dynamics of the incidence of TKR and THR according to the national registers of different countries. The issues of the complication risks in patients with RA and OA, current recommendations for anti-rheumatic therapy in RA in the perioperative period are also considered.

Rheumatoid arthritis epidemiology: a nationwide study in Poland.

To assess the incidence and prevalence of rheumatoid arthritis (RA) in Poland for the period 2013-2021, total and dependent on gender, age, region and serological status. Information on reported National Health Fund (NHF) health services and reimbursed prescriptions were used, defining an RA patient as a person who had at least two visits in different quarters with ICD-10 code M05 or M06 and at the same time filled at least one reimbursed prescription for a drug whose active substance is methotrexate, sulfasalazine, leflunomide or was treated with biologic disease-modifying anti-rheumatic drugs (bDMRDs) or targeted synthetic DMARDs (tsDMARDs) as part of a drug program financed by the National Health Fund. The nationwide standardised incidence rate of RA in 2021 was 29 persons per 100,000 population (18 per 100,000 population of seropositive vs. 11 per 100,000 population of seronegative RA). The prevalence of RA in Poland in 2021 was 689.0 people per 100,000 population, a total of 0.7% (1.1% in women and 0.3% in men). The incidence of seronegative RA was approximately 38%. The majority of new RA diagnoses were in the sixth and seventh decades of life, irrespective of patients' gender. The results allow RA to be classified as a disease with a significant social impact. A trend of later onset of RA has been observed, which requires special consideration of the needs of patients over 55years of age.

OA36 Systemic juvenile idiopathic arthritis: the Great Ormond Street Hospital experience (2005-2021)

Abstract Background/Aims sJIA is a complex, systemic-inflammatory disorder. The proposed biphasic model of disease suggests that unchecked early auto-inflammation driven by increased innate immune activation, including dysregulation of IL-1 and IL-6, may lead to a state of chronic T-lymphocyte activation. This leads to an unfavourable balance of T-effector and regulatory cells that can drive chronic arthritis over time. It is therefore unsurprising that there is growing evidence to support instigation of IL-1 or IL-6 blockade as first-line treatment in sJIA. Early cytokine antagonist therapy could abrogate development of a population of these arthritis-causing T-cells to avert chronic systemic inflammation and arthritis. Aims: 1) describe clinical presentations, therapeutic interventions, complications, and remission rates at different time-points over disease course in sJIA; 2) identify potential therapeutic signals in patients with sJIA who received biologic treatment early in disease course compared to those who did not. Methods Retrospective review of all patients with sJIA at GOSH (02/10/05-21/10/21, inclusive). Data collected: patient demographics; clinical and laboratory data; treatment history; adverse events. Time-points for data collection: at diagnosis; 3-months; 1-year; last follow-up. Descriptive statistics reported as median and range or IQR for continuous variables, and as absolute frequencies and percentages for categorical variables. Comparisons of quantitative variables were made by Mann-Whitney U-test. Categorical data were compared using Fisher’s exact test (p-values&amp;lt;0.05 were considered significant). Results A total of 76 children (female n = 40, 53%) were diagnosed with sJIA; median age was 4.5 years (range 0.6-14.1). 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% versus 53%, p = 0.002). Conclusion We propose a UK treatment-algorithm for children diagnosed with sJIA (see figure). We recommend reappraisal of the current NHS England commissioning policy. Disclosure C. Foley: None. D. McKenna: None. K. Gallagher: None. K. McLellan: None. H. Alkhdher: None. S. Lacassagne: None. E. Moraitis: None. C. Papadopoulou: None. C. Pilkington: None. M. Al Obaidi: None. D. Eleftheriou: None. P. Brogan: None.

E067 Bimekizumab maintained efficacy responses through 52 weeks in biologic disease-modifying antirheumatic drugnaïve patients with psoriatic arthritis who were responders at week 16: results from BE OPTIMAL, a phase 3, activereference study

Abstract Background/Aims Given the chronic nature of psoriatic arthritis (PsA), sustaining high levels of disease control with treatment is important. Assessing maintenance of response in patients that achieve treatment targets is of interest as loss of response can occur with long-term therapy. Bimekizumab (BKZ), a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A, has demonstrated rapid, clinically meaningful joint and skin efficacy responses at Week (Wk) 16 versus placebo (PBO) in patients with PsA; responses were sustained to Wk52. We report the maintenance of response in joint and skin efficacy outcomes to 52 wks in BKZ-treated patients with PsA who responded at Wk16. Methods BE OPTIMAL (NCT03895203), which included a 16-wk double-blind, PBO-controlled period and a 36-wk active treatment-blind period, assessed BKZ in biologic disease-modifying antirheumatic drug (DMARD)-naïve patients with active PsA. Patients were randomised 3:2:1 to subcutaneous BKZ 160mg every 4 wks (Q4W), PBO or reference (adalimumab 40mg Q2W). At Wk16, PBO patients switched to BKZ 160mg Q4W. Maintenance of response is reported as the percentage of BKZ-treated patients who achieved response at Wk16 and maintained at Wk52. Data are reported for patients randomised to BKZ 160mg Q4W at baseline. Endpoints include American College of Rheumatology (ACR)20/50/70, Psoriasis Area and Severity Index (PASI)75/90/100, minimal/very low disease activity (MDA/VLDA) and Disease Activity Index for PSoriatic Arthritis (DAPSA) remission or low disease activity (REM+LDA; ≤14) and remission (REM; ≤4) responses. Wk16 responders are reported using nonresponder imputation (NRI); maintenance of response to Wk52 is reported using NRI and observed case (OC). Treatment-emergent adverse events (TEAEs) to Wk52 are reported for patients who received ≥1 dose of BKZ, including patients randomised to PBO at baseline. Results At baseline, 431 patients were randomised to BKZ 160mg Q4W; 217/431 (50.3%) had psoriasis affecting ≥3% body surface area (BSA). 414/431 (96.1%) completed Wk16; 388 (90.0%) completed Wk52. Most patients who achieved response at Wk16 maintained at Wk52 across a range of joint and skin outcomes. At Wk16, 268 (62.2%)/189 (43.9%)/105 (24.4%) patients achieved ACR20/50/70; responses were maintained at Wk52 by 88.4%/86.8%/82.9% (NRI); 92.9%/91.1%/87.9% (OC). Of 217 patients with psoriasis affecting ≥3% BSA at baseline, 168 (77.4%)/133 (61.3%)/103 (47.5%) achieved PASI75/90/100 at Wk16. Most patients maintained response at Wk52: 88.1%/82.7%/79.6% (NRI); 98.7%/94.0%/89.1% (OC). The same pattern was observed for composite measures of efficacy. 194(45.0%) patients achieved MDA at Wk16; 85.6% (NRI)/90.7% (OC) maintained response at Wk52. At Wk16, 205 (47.6%)/47 (10.9%) achieved DAPSA REM+LDA/DAPSA REM; 85.9%/68.1% maintained response at Wk52. To Wk52, 555/702 (79.1%) BKZ-treated patients reported ≥1 TEAE; 46 (6.6%) reported serious TEAEs. Conclusion With BKZ treatment, most Wk16 responders maintained robust efficacy responses to Wk52 across joint, skin and composite efficacy outcomes. Safety profile of BKZ was consistent with previous reports. Disclosure W.R. Tillett: Consultancies; AbbVie, Amgen, Celgene, Eli Lilly, GSK, Janssen, MSD, Novartis, Ovo Pharma, Pfizer and UCB Pharma. Honoraria; AbbVie, Amgen, Celgene, Eli Lilly, GSK, Janssen, MSD, Novartis, Ovo Pharma, Pfizer and UCB Pharma. Grants/research support; AbbVie, Amgen, Celgene, Eli Lilly, GSK, Janssen, MSD, Novartis, Ovo Pharma, Pfizer, UCB Pharma. Other; Speaking fees from AbbVie, Amgen, Celgene, Eli Lilly, GSK, Janssen, MSD, Novartis, Ovo Pharma, Pfizer and UCB Pharma. J.F. Merola: Consultancies; AbbVie, Amgen, Biogen, BMS, Dermavant, Eli Lilly, Janssen, LEO Pharma, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma and UCB Pharma. Other; Investigator for AbbVie, Amgen, Biogen, BMS, Dermavant, Eli Lilly, Janssen, LEO Pharma, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma and UCB Pharma. Y. Tanaka: Honoraria; AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Chugai, Eisai, Eli Lilly, Gilead, GSK, Pfizer, Taiho and Taisho. Grants/research support; Chugai, Mitsubishi-Tanabe and Taisho. Other; Speaking fees from AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Chugai, Eisai, Eli Lilly, Gilead, GSK, Pfizer, Taiho and Taisho. E.G. Favalli: Consultancies; AbbVie, BMS, Celltrion, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer and UCB Pharma. Other; Speaking fees from AbbVie, BMS, Celltrion, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer and UCB Pharma. D. McGonagle: Consultancies; AbbVie, Celgene, Janssen, Merck, Novartis, Pfizer and UCB Pharma. Honoraria; AbbVie, Celgene, Janssen, Merck, Novartis, Pfizer and UCB Pharma. Member of speakers’ bureau; AbbVie, Celgene, Janssen, Merck, Novartis, Pfizer and UCB Pharma. Grants/research support; AbbVie, Celgene, Janssen, Merck, Novartis and Pfizer. J.A. Walsh: Consultancies; AbbVie, Amgen, Eli Lilly, Janssen, Merck, Novartis, Pfizer and UCB Pharma. Grants/research support; AbbVie, Amgen, Eli Lilly, Janssen, Merck, Novartis, Pfizer and UCB Pharma. D. Thaçi: Consultancies; AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Eli Lilly, Galapagos, Galderma, Janssen-Cilag, Kyowa Kirin, LEO Pharma, Novartis, Pfizer, Regeneron, Samsung, Sandoz, Sanofi, Target-Solution and UCB Pharma. Grants/research support; AbbVie, LEO Pharma and Novartis. Other; Investigator for AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Eli Lilly, Galapagos, Galderma, Janssen-Cilag, Kyowa Kirin, LEO Pharma, Novartis, Pfizer, Regeneron, Samsung, Sandoz, Sanofi, Target-Solution and UCB Pharma. B. Ink: Shareholder/stock ownership; AbbVie, GSK and UCB Pharma. Other; Employee of UCB Pharma. R. Bajracharya: Shareholder/stock ownership; UCB Pharma. Other; Employee of UCB Pharma. V. Taieb: Shareholder/stock ownership; UCB Pharma. Other; Employee of UCB Pharma. C.T. Ritchlin: Consultancies; AbbVie, Amgen, Eli Lilly, Gilead, Janssen, Novartis, Pfizer and UCB Pharma. Grants/research support; AbbVie.

Management of pregnancy in autoimmune rheumatic diseases: maternal disease course, gestational and neonatal outcomes and use of medications in the prospectiveItalian P-RHEUM.it study

ObjectivesTo investigate pregnancy outcomes in women with autoimmune rheumatic diseases (ARD) in the Italian prospective cohort study P-RHEUM.it.MethodsPregnant women with different ARD were enrolled for up to 20 gestational weeks...

P171 Bimekizumab impact on core group for research and assessment of psoriasis and psoriatic arthritis domains for patients with psoriatic arthritis: 52-week results from four phase 3 studies

Abstract Background/Aims The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (PsA; GRAPPA) domainbased treatment recommendations for PsA focus on six domains: peripheral arthritis, axial disease, enthesitis, dactylitis, skin psoriasis, and nail psoriasis, and PsA-related conditions: uveitis and IBD. Bimekizumab (BKZ), a monoclonal IgG1 antibody that selectively inhibits IL17F in addition to IL17A, has superior clinical efficacy vs placebo (PBO) to Week (Wk)16 in phase 3 clinical trials of PsA patients. In patients with psoriasis, superior skin domain efficacy was demonstrated versus secukinumab (IL-17A inhibitor), ustekinumab (IL-12/23 inhibitor), and adalimumab (TNF inhibitor [TNFi]). Methods Included patients received subcutaneous BKZ 160 mg or PBO every 4-wks (Q4W) in BE OPTIMAL (NCT03895203; biologic disease-modifying antirheumatic drugs [bDMARD]naïve patients with PsA), BE COMPLETE (NCT03896581; patients with PsA who were TNFiinadequate responders [TNFiIR]), BE MOBILE 1 (NCT03928704; nonradiographic axial spondyloarthritis [nr-axSpA]) and BE MOBILE 2 (NCT03928743; radiographic [r-]axSpA [i.e. ankylosing spondylitis]). BE OPTIMAL included a reference arm (adalimumab 40 mg Q2W) to Wk52; data not shown. From Wk16, all PBO-randomised patients received BKZ 160 mg Q4W to Wk52 (PBO/BKZ). Wk16 completers from BE COMPLETE entered BE VITAL (NCT04009499; openlabel extension). Outcomes are reported by GRAPPA domain as change from baseline and/or responder rate. Missing data were imputed using non-responder (binary) or multiple (continuous) imputation. Results Wk52 completion was high (BE OPTIMAL: 770/852 [90.4%], BE COMPLETE: 347/400 [86.8%], BE MOBILE 1: 220/254 [86.6%], BE MOBILE 2: 298/332 [89.8%]). Baseline demographics and disease characteristics were previously reported. Across all GRAPPA domains, improvements from Wk16 were sustained at Wk52 in BKZ-treated patients across all studies. Individual domain responses were generally consistent between bDMARD naïve and TNFi-IR patients; results from BE MOBILE 1 and 2 demonstrated BKZ efficacy in patients with axSpA (Table). Responses were generally consistent between BKZ and PBO/BKZ patients at Wk52. To Wk52, there were low rates of adjudicated IBD (2 [0.2%] in BE OPTIMAL) and no instances of uveitis. Conclusion Treatment with BKZ resulted in robust and sustained improvements across GRAPPA domains to Wk52 for both bDMARD naïve and TNFi-IR patients with PsA; results from patients with axSpA support efficacy in the axial domain. Disclosure J.F. Merola: Consultancies; AbbVie, Amgen, Biogen, BMS, Dermavant, Eli Lilly, Janssen, LEO Pharma, Pfizer, Novartis, Regeneron, Sanofi, Sun Pharma, and UCB Pharma. Other; Investigator for AbbVie, Amgen, Biogen, BMS, Dermavant, Eli Lilly, Janssen, LEO Pharma, Pfizer, Novartis, Regeneron, Sanofi, Sun Pharma, and UCB Pharma. P.J. Mease: Consultancies; AbbVie, Acelyrin, Aclaris, Amgen, BMS, Boehringer Ingelheim, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Moonlake Pharma, Novartis, Pfizer, Sun Pharma and UCB Pharma. Member of speakers’ bureau; AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma. Grants/research support; AbbVie, Acelyrin, Amgen, BMS, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Sun Pharma and UCB Pharma. A. Deodhar: Consultancies; AbbVie, BMS, Eli Lilly, Janssen, MoonLake, Novartis, Pfizer, UCB Pharma. Member of speakers’ bureau; Janssen, Novartis, Pfizer. Grants/research support; AbbVie, BMS, Celgene, Eli Lilly, MoonLake, Novartis, Pfizer, UCB Pharma. B. Ink: Shareholder/stock ownership; AbbVie, GSK, UCB Pharma. Other; Employee of UCB Pharma. C. Fleurinck: Other; Employee of UCB Pharma. R. Bajracharya: Shareholder/stock ownership; UCB Pharma. Other; Employee of UCB Pharma. J. Coarse: Shareholder/stock ownership; UCB Pharma. Other; Employee of UCB Pharma. L.C. Coates: Consultancies; AbbVie, Amgen, BMS, Boehringer Ingelheim, Celgene, Domain, Eli Lilly, Galapagos, Gilead, Janssen, Moonlake Pharma, Novartis, Pfizer, UCB Pharma. Member of speakers’ bureau; AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, GSK, Janssen, medac, Novartis, Pfizer, UCB Pharma. Grants/research support; AbbVie, Amgen, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, UCB Pharma.

P046 The influence of deprivation in the outcomes of Psoriatic Arthritis within the UK - utilising Outcomes of Treatment in Psoriatic Arthritis Study Syndicate data

Abstract Background/Aims Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy, which affects approximately 30% of patients with psoriasis and is associated with a high degree of morbidity. The introduction of biological disease-modifying antirheumatic drugs (bDMARDs) revolutionised treatment strategies for patients with PsA, however response is not universal. Deprivation and its associated risk factors may impact the initiation of and response to treatment with bDMARDs. There is limited data exploring the effect of deprivation on disease response to biologics in PsA. Psoriasis patients with a higher socioeconomic status have been shown to be more likely to respond to biologics, to our knowledge this has not been investigated in PsA. This study aimed to assess the impact of deprivation on initiation of and clinical response to biologic DMARDs. Methods Patients commencing a bDMARD were recruited to the UK prospective observational study Outcome of Treatment in Psoriatic Arthritis Studies Syndicate (OUTPASS REC ref:13/NW/0068). Index of Multiple Deprivation (IMD), the official measure of relative deprivation in England, was the exposure of interest. Subjects were ranked based on their IMD and split into the 20% most deprived (deciles 1-2), middle 40% (deciles 3-6) and 40% least deprived (deciles 7-10). This was done to aid analysis as IMD weightings provide greater differentiation among the least advantaged areas with fewer distinctions for less deprived areas. Treatment response was measured using changes in DAS28/PsARC, analysed using multivariate linear regression and multivariate logistic regression, respectively. Response was measured at three months as NICE guidance advises review of biological therapies at this time. Results There was no difference in the distribution of patients between the three groups (most deprived=138, middle deprived=207, least deprived=193). There were no statistically significant differences in the time from diagnosis to starting biologics in the most deprived group compared to the middle (p = 0.62) or least deprived p = 0.42) groups. There was no statistically significant difference in treatment responses between the groups. DAS28 change and PsARC improvement at three months remained similar between the most deprived, the middle deprived (p = 0.71, p = 0.08) and least deprived groups (p = 0.81, p = 0.22). Conclusion There was no difference in the distribution of IMD in patients recruited to OUTPASS, suggesting that the study is inclusive in recruiting across IMD subgroups. There was no difference in time from diagnosis to starting bDMARD therapy or response to treatment across the deprivation spectrum. These findings suggest that the NHS in England is performing its role of providing care according to need and regardless of circumstance. The study assesses deprivation in the context of free healthcare and may not be applicable to fee-paying healthcare systems. Further research is required to determine the relationship between deprivation and other outcomes, including work instability, in PsA. Disclosure M. Lyon: None. S. Zhao: None. A. Barton: Member of speakers’ bureau; speaker fees from Chugai-Roche and Galapagos. Grants/research support; grant funding from BMS, Pfizer, all unrelated to the work presented. H. Chinoy: Corporate appointments; Advisory Board member for Astra Zeneca, Pfizer, Argenx, Galapagos; Data and Science Monitoring Board chair for Horizon Therapeutics.. Consultancies; Consulting for PTC Therapeutics. Member of speakers’ bureau; fees as a speaker for GSK, UCB. M. Jani: None. J. Bluett: Grants/research support; research grant award from Pfizer and travel/conference fees from UCB, Fresenius Kabi, Pfizer and Eli Lilly.

OA05 Potential impact of European Medicines Agency measures to minimise risk of serious side effects on those using JAK inhibitors in the UK

Abstract Background/Aims Janus kinase inhibitors (JAKi) are effective therapies for rheumatoid arthritis (RA). However, concerns about their safety in certain 'at-risk' populations have resulted in risk minimisation measures introduced by European Medicines Agency (EMA) in January 2023, which limits JAKi prescription to certain patient subgroups unless no suitable alternative is available. The potential impact on current and future JAKi use in the UK is unknown. Using a national cohort study of patients who have already started their first JAKi, this analysis aimed to describe the proportion meeting ≥1 of these criteria and therefore may be impacted by these changes. Methods RA patients starting their first-ever JAK inhibitor (tofacitinib, baricitinib, upadacitinib, or filgotinib) therapy in the British Society for Rheumatology RA Biologics Register (BSRBR-RA) before 31st May 2022 (pre-EMA warning) were included. Patients with missing data in any EMA criteria related variables were excluded. Descriptive statistics were used to present patients' characteristics at the start of JAKi. This analysis defined four at-risk criteria assessed at the treatment start: 1) aged ≥65; 2) increased risk of major cardiovascular issues (history of hypertension, hyperlipidaemia, diabetes, ischaemic heart disease, or stroke); 3) current or past smokers; 4) increased risk of cancer (defined as prior cancer). The previous number of distinct biological disease-modifying antirheumatic drugs (bDMARDs) classes was described among those who met the criteria. Results A total of 1,362 patients starting their first JAKi were included, most commonly baricitinib (76%), followed by tofacitinib (16%; see Table). The cohort was 78% female, with an average age of 60. Among them, 28% of patients had received ≥3 prior bDMARDs classes. 80% percent of patients (1,090) met ≥1 EMA risk criterion, with the most common individual criterion current/past smoker (54%). Of those who met ≥1 risk criteria, 645 (59%) met ≥1 EMA risk criterion and 29% had already received ≥3 prior bDMARDs classes. Conclusion A very high proportion of patients, four-in-five, initiating JAKi in UK before the EMA advisory would have fallen into the ‘high-risk' category for whom prescribing would only be advised if no suitable alternatives were available. Whilst almost a third of them had previously received ≥3 different bDMARDs classes, it’s likely that many of them would have suitable alternatives. These data highlight the enormous impact of the recent licensing updates for JAKi class. Disclosure Z. Tian: None. L. Kearsley-fleet: None. J. Galloway: Honoraria; Abbvie, Galapagos, Janssen, Lilly, Novartis, Pfizer, UCB, Vifor. Grants/research support; Abbvie, Galapagos, GSK, Janssen, Pfizer. K. Watson: None. M. Lunt: None. K.L. Hyrich: Honoraria; Abbvie. Grants/research support; Pfizer, BMS.

P108 Filgotinib for Rheumatoid Arthritis: an observational cohort to assess clinical effectiveness in a single centre

Abstract Background/Aims Filgotinib, a Janus-kinase (JAK) 1 preferential inhibitor, was approved for use in the UK in moderate or severe rheumatoid arthritis (RA) in 2021, as monotherapy or in combination with Methotrexate. Evidence of real-world effectiveness is currently limited. Methods Patients prescribed Filgotinib between December 2021 and August 2022 in NHS Lothian were identified from pharmacy registration data. All underwent clinical efficacy assessment at three months. Electronic patient records (EPR) were reviewed to record baseline data including previous and current treatments. Duration of Filgotinib treatment was recorded, and discontinuation reason if applicable. DAS-28 scores within six months prior to starting Filgotinib were recorded, along with available subsequent scores. Pre-existing interstitial lung disease (ILD), venous thromboembolism (VTE), major adverse cardiovascular events (MACE) and malignancy were recorded, along with incident events during treatment. Results 145 patients were prescribed Filgotinib; 106 (73.1%) females and 39 (26.9%) males, with median age 64 years. Median treatment duration was 447 days. 35 (24.1%) were treated with the reduced 100mg dose. 81 (55.9%) received conventional disease-modifying anti-rheumatic drugs (DMARDs) alongside Filgotinib. 41 (28.3%) patients discontinued treatment: 10 (6.9%) due to loss of effect; 16 (11.0%) due to lack of efficacy; six (4.1%) experienced side effects leading to cessation; five (3.4%) stopped for alternative reasons; one (0.7%) experienced a severe allergic drug reaction; three (2.1%) developed lung cancer and treatment was stopped in each case. 12 (8.3%) patients had ILD prior to treatment. 10 (6.9%) had prior major cardiovascular events, eight (5.5%) had previously treated malignancy, and six (4.1%) had previous VTE. During treatment, 1 (0.7%) patient developed ILD and two (1.4%) developed VTE. There were three (2.1%) new malignancies, all lung cancer. No new MACE occurred. 120 (82.8%) patients were previously treated with biologic or targeted synthetic DMARDs. 59 (40.7%) had failed multiple biologic DMARDs of different classes. 19 (13.1%) switched to Filgotinib from another JAK inhibitor. Pre-treatment DAS-28 scores were recorded in 55 (37.9%) patients with mean 5.1, and during treatment in 44 patients (30.3%) with mean 3.5. 17 (11.7%) patients had DAS-28 recorded both before and during treatment, with pre-treatment mean 5.0 and subsequent mean 2.9. Of these, 10 (58.8%) were classified as a good response by EULAR disease activity criteria, and four (23.5%) as a moderate response. Three (17.6%) were non-responders. Conclusion Our cohort includes 40.7% difficult-to-treat RA. Drug survival as a clinical efficacy surrogate was 71.7% at median duration 447 days, demonstrating patient acceptability and clinical effectiveness. Our service is poor at DAS-28 recording in the EPR, which may partly reflect imaging use at response assessment. Since this cohort was established, the European Medicines Agency has issued guidance advising caution using JAK inhibitors in high-risk groups to minimise the chance of serious side effects. Disclosure C.D. Box: None. S. Ramsay: None. N.D. McKay: Other; N.D.M. has received funding for conference registrations from Abbvie, UCB and Novartis, fees for lecturing from Gilead, and has taken part in advisory board meetings for UCB and Gilead.

BDMARD can prevent the progression of AA amyloidosis to end-stage renal disease.

AA amyloidosis (AA) can be the consequence of any chronic inflammatory disease. AA is associated with chronic inflammatory diseases (cid+AA), autoinflammatory syndromes (auto+AA) or AA of unknown origin or idiopathic AA (idio+AA). The major organ manifestation is renal AA that can progress to end-stage renal disease (ESRD) and multiple organ failure. This study is a monocentric retrospective analysis of the renal outcome and survival of patients with cid+AA (n=34), auto+AA (n=24) and idio+AA (n=25) who were treated with cytokine-inhibiting biological disease-modifying antirheumatic drugs (bDMARDs). 83 patients with renal AA were identified and followed for a mean observational period of 4.82 years. C reactive protein (CRP), serum amyloid alpha and proteinuria were significantly reduced with bDMARD therapy. Progression to ESRD was prevented in 60% (cid+AA), 88% (auto+AA) and 81% (idio+AA) of patients. Tocilizumab was given to 34 patients with cid+AA and idio+AA and was more effective in reducing CRP and progression to ESRD and death compared with other bDMARDs. bDMARDs reduce systemic inflammation in various diseases, leading to a reduction of proteinuria and prevention of ESRD. Importantly, tocilizumab was more effective than other bDMARDs in controlling systemic inflammation in patients with chronic inflammatory diseases and idiopathic AA, leading to better renal and overall survival.

Drug therapy in juvenile spondyloarthritis.

This review summarizes latest developments in treatment of juvenile spondyloarthritis (JSpA), specifically enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA). There has been addition of biologic disease modifying antirheumatic drugs (bDMARDs) beyond tumor necrosis factor inhibitors (TNFi) for JSpA such as IL-17 blockers, IL-23 blockers, and janus activating kinase inhibitors with favorable safety profile. Conducting robust clinical trials for this subpopulation of JIA remains a challenge; extrapolation studies are being used to obtain approval from regulatory agencies. Newer drug therapies have expanded the scope of treatment for patients with JSpA. bDMARDs such as adalimumab, etanercept, infliximab, and secukinumab have demonstrated clinically significant treatment efficacy in ERA and JPsA. Based on extrapolation studies, intravenous golimumab, etanercept, abatacept, and ustekinumab have gained Food and Drug Administration (FDA) approval for JPsA. Long-term follow-up studies continue to demonstrate acceptable safety profiles. There is need for more real-world data on drug efficacy from Registry studies and research on effective de-escalation strategies.

The role of repeat kidney biopsy in patients with lupus nephritis (case report)

Lupus nephritis (LN) occurs in 35–60% of patients with systemic lupus erythematosus (SLE), often in the early stages of the disease. LN is one of the most severe manifestations of SLE and, if not treated promptly and effectively, can lead to rapid and severe loss of kidney function. Despite modern pharmacotherapy, 5–20% of patients develop end-stage renal failure within 10 years of diagnosis of LN. The main principle of LN therapy is to prevent deterioration of renal function, but a consensus on outcome assessment criteria and clinically relevant short- and long-term goals for LN therapy has not yet been reached. There is increasing evidence of the importance of repeat kidney biopsies to assess the outcomes of the initial phase of therapy and to determine the long-term prognosis of renal failure. It is believed that the information obtained from repeat biopsies can help to make optimal treatment decisions and thus increase the likelihood of achieving a complete renal response in the short term and a more favorable renal prognosis in the long term.We describe a clinical case of a young patient with highly active SLE and morphologically confirmed class IV-S LN. Repeat biopsy and clinical and laboratory examination, had confirmed a clinical and laboratory remission of the disease on the background of the therapy. This made it possible to reduce the dose of methylpednisolone and cytostatic drugs (mycophenolate mofetil) and to discontinue therapy with biologic diseasemodifying antirheumatic drug (rituximab).