Explore the vast range of titles available.

Objectives To compare the effectiveness of rituximab versus an alternative tumour necrosis factor (TNF) inhibitor (TNFi) in patients with rheumatoid arthritis (RA) with an inadequate response to one previous TNFi. Methods SWITCH-RA was a prospective, global, observational, real-life study. Patients non-responsive or intolerant to a single TNFi were enrolled ≤4 weeks after starting rituximab or a second TNFi. Primary end point: change in Disease Activity Score in 28 joints excluding patient's global health component (DAS28-3)–erythrocyte sedimentation rate (ESR) over 6 months. Results 604 patients received rituximab, and 507 an alternative TNFi as second biological therapy. Reasons for discontinuing the first TNFi were inefficacy (n=827), intolerance (n=263) and other (n=21). A total of 728 patients were available for primary end point analysis (rituximab n=405; TNFi n=323). Baseline mean (SD) DAS28-3–ESR was higher in the rituximab than the TNFi group: 5.2 (1.2) vs 4.8 (1.3); p<0.0001. Least squares mean (SE) change in DAS28-3–ESR at 6 months was significantly greater in rituximab than TNFi patients: −1.5 (0.2) vs −1.1 (0.2); p=0.007. The difference remained significant among patients discontinuing the initial TNFi because of inefficacy (−1.7 vs −1.3; p=0.017) but not intolerance (−0.7 vs −0.7; p=0.894). Seropositive patients showed significantly greater improvements in DAS28-3–ESR with rituximab than with TNFi (−1.6 (0.3) vs −1.2 (0.3); p=0.011), particularly those switching because of inefficacy (−1.9 (0.3) vs −1.5 (0.4); p=0.021). The overall incidence of adverse events was similar between the rituximab and TNFi groups. Conclusions These real-life data indicate that, after discontinuation of an initial TNFi, switching to rituximab is associated with significantly improved clinical effectiveness compared with switching to a second TNFi. This difference was particularly evident in seropositive patients and in those switched because of inefficacy.

Objectives Rituximab is an effective treatment in patients with established rheumatoid arthritis (RA). The objective of the IMAGE study was to determine the efficacy of rituximab in the prevention of joint damage and its safety in combination with methotrexate (MTX) in patients initiating treatment with MTX. Methods In this double-blind randomised controlled phase III study, 755 MTX-naïve patients with active RA were randomly assigned to MTX alone, rituximab 2×500 mg + MTX or rituximab 2×1000 mg + MTX. The primary end point at week 52 was the change in joint damage measured using a Genant-modified Sharp score. Results 249, 249 and 250 patients were randomly assigned to MTX alone, rituximab 2×500 mg + MTX or rituximab 2×1000 mg + MTX, respectively. At week 52, treatment with rituximab 2×1000 mg + MTX compared with MTX alone was associated with a reduction in progression of joint damage (mean change in total modified Sharp score 0.359 vs 1.079; p=0.0004) and an improvement in clinical outcomes (ACR50 65% vs 42%; p<0.0001); rituximab 2×500 mg + MTX improved clinical outcomes (ACR50 59% vs 42%; p<0.0001) compared with MTX alone but did not significantly reduce the progression of joint damage. Safety outcomes were similar between treatment groups. Conclusions Treatment with rituximab 2×1000 mg in combination with MTX is an effective therapy for the treatment of patients with MTX-naïve RA. CLinicalTrials.gov identifier NCT00299104.

ObjectivesThe efficacy of tocilizumab (TCZ), an anti-interleukin-6 receptor antibody, has not previously been evaluated in a population consisting exclusively of patients with early rheumatoid arthritis (RA).MethodsIn a double-blind randomised controlled trial (FUNCTION), 1162 methotrexate (MTX)-naive patients with early progressive RA were randomly assigned (1:1:1:1) to one of four treatment groups: 4 mg/kg TCZ+MTX, 8 mg/kg TCZ+MTX, 8 mg/kg TCZ+placebo and placebo+MTX (comparator group). The primary outcome was remission according to Disease Activity Score using 28 joints (DAS28–erythrocyte sedimentation rate (ESR) <2.6) at week 24. Radiographic and physical function outcomes were also evaluated. We report results through week 52.ResultsThe intent-to-treat population included 1157 patients. Significantly more patients receiving 8 mg/kg TCZ+MTX and 8 mg/kg TCZ+placebo than receiving placebo+MTX achieved DAS28-ESR remission at week 24 (45% and 39% vs 15%; p<0.0001). The 8 mg/kg TCZ+MTX group also achieved significantly greater improvement in radiographic disease progression and physical function at week 52 than did patients treated with placebo+MTX (mean change from baseline in van der Heijde–modified total Sharp score, 0.08 vs 1.14 (p=0.0001); mean reduction in Health Assessment Disability Index, −0.81 vs −0.64 (p=0.0024)). In addition, the 8 mg/kg TCZ+placebo and 4 mg/kg TCZ+MTX groups demonstrated clinical efficacy that was at least as effective as MTX for these key secondary endpoints. Serious adverse events were similar among treatment groups. Adverse events resulting in premature withdrawal occurred in 20% of patients in the 8 mg/kg TCZ+MTX group.ConclusionsTCZ is effective in combination with MTX and as monotherapy for the treatment of patients with early RA.Trial registration numberClinicalTrials.gov, number NCT01007435

ObjectiveInvestigate whether the efficacy and safety of intravenous tocilizumab (TCZ) demonstrated at week 52 in patients with early rheumatoid arthritis (RA) are maintained to week 104.MethodsMethotrexate (MTX)-naive patients with early progressive RA were randomly assigned to double-blind 4 mg/kg TCZ+MTX, 8 mg/kg TCZ+MTX, 8 mg/kg TCZ+placebo or placebo+MTX for 104 weeks. Patients not receiving 8 mg/kg TCZ and not achieving Disease Activity Score-28 joints (DAS28-erythrocyte sedimentation rate (ESR)) ≤3.2 at week 52 switched to escape therapy (8 mg/kg TCZ+MTX). Analyses were exploratory.ResultsIntent-to-treat and safety populations included 1157 and 1153 patients, respectively. DAS28-ESR remission (<2.6) rates were maintained from weeks 52 to 104 (eg, 8 mg/kg TCZ+MTX, 49.3% to 47.6%). Placebo+MTX and 4 mg/kg TCZ+MTX escape patients' week 104 response rates were 51.4% and 30.5%, respectively. Inhibition of radiographic progression was maintained with 8 mg/kg TCZ (eg, 8 mg/kg TCZ+MTX mean (SD) change from baseline in modified total Sharp score: 0.13 (1.28), week 52; 0.19 (2.08), week 104). The safety profile of TCZ was consistent with that of previous reports.ConclusionsPatients with early RA treated with TCZ monotherapy or TCZ+MTX maintained clinical benefits during their second year of treatment with no new safety signals.Trial registration number:NCT01007435; Results.

Background:Systemic lupus erythematosus (SLE) may potentially affect different organs with kidney involvement representing the most significant organ manifestation. There is a need for biomarkers indicating active disease and an early detection of renal disease. Expression of CD169 (SIGLEC1) on peripheral blood monocytes has been proposed as a surrogate for a dominant type I IFN signature and increased disease activity1.Objectives:To study CD169 expression on urine and peripheral blood monocytes in correlation to clinical characteristics and serological markers of disease activity.Methods:64 patients from the St. Gallen SLE cohort, also enrolled in the Swiss SLE Cohort Study (SSCS), were consecutively recruited into this prospective cross-sectional, observational study and compared to 14 age- (39 [32-49] years) and sex (female 12/14 (86%)) matched healthy controls (HC). Expression of CD169 on urine and peripheral blood monocytes was assessed using quantitative flow cytometry.2 Clinical assessment included SELENA-SLEDAI, PGA, SF-36, SLICC/ACR damage index and laboratory parameters as shown in Table 1.Independent associations of continuous and categorical variables were analysed by of variance (ANOVA) models, using the general linear model approach. Correlation analyses were performed calculating parametric Spearman correlation coefficients.Results:37.5% of SLE patients had active disease with a SELENA-SLEDAI ≥4 and 14/64 (22%) of SLE patients had biopsy proven lupus nephritis class III-V. Expression of CD169 on peripheral blood monocytes in SLE patients was significantly higher compared to age and sex matched HC (p = 0.0016) while it was significantly lower on urine monocytes (Figure 1A). In SLE patients, CD 169 expression on peripheral blood monocytes positively correlated with disease activity (SELENA-SLEDAI) (r = 0.384, p = 0.002) (Figure 1B), ESR (r = 0.341, p = 0.006), and anti-dsDNA antibodies levels (r = 0.513, p < 0.0001), while an inverse correlation was observed with C3c (r = - 0.290, p = 0.021) and C4 (r = - 0.258, p = 0.04) levels. Moreover, biopsy proven renal manifestation (r = 0.419, p = 0.001), fever (r = 0.551, p < 0.0001), rash (r = 0.322, p = 0.01), and leucopenia (r = 0.334, p = 0.007) were associated with expression of CD169 on blood monocytes.Baseline characteristics of patients with and without renal disease are detailed in Table 1. CD169 expression on urine monocytes was comparable when analyzing spot-, 12-hour (h)-, and 24-h urine samples. A decreased CD169 expression on urine monocytes (<20%) was detected in 67% of SLE patients, in all patients with biopsy proven nephritis, and in 38% of HC (p = 0.0006). A lower CD169 expression on urine monocytes was associated with an increase in SELENA-SLEDAI (r = 0.280, p = 0.026), with biopsy proven renal manifestation (r = 0.262, p = 0.038) (Figure 1C), an increased albumin/creatinine ratio (r = 0,351 p = 0.005) (Figure 1D) and with serum creatinine levels (r = -0.331, p = 0.008), the presence of anti-Sm- (r = 0,457, p < 0.0001) and levels of anti-dsDNA- (r = 0,290, p = 0.021) antibodies (Table 1).Conclusion:In this cohort of SLE patients, higher expression of CD169 on peripheral blood monocytes inversely correlated with decreased CD169 expression on monocytes in urine (r = 0.336, p = 0.007), and was associated with the presence of renal disease and markers of active renal SLE disease. Our data suggest that lower CD169 expression on monocytes in urine than on monocytes in peripheral blood indicates more severe renal involvement and should be explored in more detail.REFERENCES:[1] Biesen R, et al. Arthritis Rheum 2008;58(4):1136-45[2] Stuckrad SLV, et al. Lupus 2020;29(14):1914-25Acknowledgements:We would like to thank the lupus volunteers of the Swiss SLE Cohort Study St.Gallen who made this work possible.Disclosure of Interests:None declared.

BackgroundAcetaminophen (APAP = paracetamol) may potentially impact vaccine-associated immune responses as the intake of APAP has been associated with a worse outcome in tumor patients receiving checkpoint inhibitors.[1]Different DMARD regimen have been shown to impair the humoral immune response to mRNA SARS-CoV-2 vaccines in patients with rheumatoid arthritis but the effect of paracetamol has not been explored thus far.ObjectivesTo analyse whether the intake of APAP may interfere with antiviral humoral immune responses following two doses of an anti-SARS-CoV-2 mRNA based vaccine in patients with rheumatoid arthritis (RA) on DMARD therapy.MethodsThe RECOVER trial (Rheumatoid Covid-19 Vaccine Immune Response) was a non-randomised, prospective observational control group trial and enrolled 77 RA patients on DMARD therapy and 21 healthy controls (HC). We performed a posthoc analysis of blood samples taken before the first vaccine dose (T0), two (T1) and three (T2) weeks after the first and second vaccine dose, and at 12 (T3) weeks. APAP intake was measured using ELISA. The antibody response (anti-S) to the receptor binding domain (RBD) within the SARS-CoV-2 S1 protein was measured with the Elecsys Anti-SARS-CoV-2-S (Roche Diagnostics GmbH) test. The neutralizing activity NT50 at week 12 was assessed using an HIV-based pseudovirus neutralization assay against Wuhan-Hu-1.ResultsBaseline characteristics of participants are detailed in Table 1. The immunogenicity analyses were based on 73 RA patients after exclusion of 4 patients with previously unnoticed SARS-CoV-2 infection (positive for anti-nucleoprotein at baseline). APAP was detected in serum samples from 34/73 (25%) RA patients and in 7/21 (33%) HC (least at one timepoint T0, T1 and/or T2). APAP intake in HC did not affect levels of anti-S at any timepoint and all HC developed potent neutralizing activity (NT50 ≥ 250) at week 12. RA patients, who tested positive for APAP at T1, showed comparable anti-S levels at T1, T2 and T3 compared to RA patients not exposed to APAP. The detection of APAP at T2 corresponded to lower anti-S levels at T2 (Figure 1 A, B). The detection of APAP at T2 was associated with a significantly lower SARS-CoV-2 neutralizing activity at week 12 compared to patients without perivaccination APAP exposure (p =0.04) (Figure 1 C).ConclusionA decrease of antiviral humoral immune responses was observed in RA patients (but not in HC) who were exposed to APAP at the time of the second mRNA vaccine dose compared to patients in whom APAP was not detected. Our data suggest that the use of paracetamol within the time period around vaccination may impair vaccine-induced immune responses in patients with an already higher risk for blunted immune responses.Reference[1]Bessede A et al. Ann Oncol 2022; 33: 909-915Table 1.Baseline characteristics: RA patients and HC with/without APAP exposureRAAPAP –n = 37RAAPAP +n = 36p-valueHCAPAP –n = 8HCAPAP +n = 13p-valueAge (yrs), mean (± SD)62 (13)67 (10)0.07(NS)45 (12)44 (14)0.90(NS)Female sex, n (%)24 (65)19 (53)0.29(NS)2 (25)5 (38)0.53(NS)Vaccination type/schedulemRNA-1273, n (%)4 (11)8 (22.2)0.19(NS)0 (0)0 (0)BNT162b2, n (%)33 (89)28 (77.8)0.19(NS)8 (100)13 (100)RA disease characteristicsACPA ± RF, n (%)17/37 (46)19/36 (53)0.56(NS)NANANARA disease duration (yrs ± SD)9.2 (9.8)10.2 (8.1)0.67(NS)NANANADMARD therapycsDMARD-mono, n (%)13/37(35)9/36(25)0.35(NS)NANANAbDMARD-mono/combo, n (%)16/37(43)16/36(44)0.92(NS)NANANAtsDMARDs-mono/combo, n (%)8/37(22)11/36(31)0.38(NS)NANANAPrednisone, n (%)15/37 (41)12/36 (33.3)0.52(NS)NANANAMean daily dose prednisone (mg ± SD)4.6 ± 1.13.9 ± 2.30.39(NS)NANANA* APAP = acetaminophenFigure 1.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Cystic fibrosis (CF) is characterized by mutations within the CFTR (cystic fibrosis transmembrane conductance regulator) gene that result in a defect of the chloride transporter protein in different organs, particularly in the lung. Musculoskeletal symptoms have been reported in up to 29% of CF patients [1], most frequently as recurrent episodes of mono- or polyarthritis in joints of hands and feet. Recently, potent CFTR modulator therapies targeting the F508del mutation in CF have become available (i.e., Trikafta© - consisting of a triple combination of elexacaftor, tezacaftor, and ivacaftor) that increase CFTR protein availability and function at cell surfaces. To characterize musculoskeletal symptoms in a cohort of consecutive CF patients. 25 CF patients were enrolled in this monocentric, prospective, and cross-sectional cohort study. Rheumatologic evaluation included clinical and laboratory parameters. Data were analyzed by covariance (ANCOVA) models, using the general linear model approach. Correlation analyses were performed calculating nonparametric Spearman correlation rank coefficients. Baseline characteristics are outlined in Table 1. 22/25 CF patients were under CFTR modulator treatment with a mean treatment duration of 13 + 4 months. Arthralgias and myalgias were reported in 48% and 20% of patients, respectively. Arthritis, mainly involving small joints, was clinically detected in 6/25 (24%) patients and confirmed by ultrasound (US) in 3/6 patients. Self-reported myalgias, but not self-reported arthralgias, were significantly associated with the presence of swollen joints (r = 0.7452, p < 0.0001), tender joints, (r = 0.6674, p = 0.0003), a positive squeeze test (r = 0.5898, p = 0.0019) and morning stiffness (r = 0.6556, p = 0.0004) (Table 1). Disease activity as assessed by the Simplified Disease Activity Index (SDAI) was moderate (mean 18 + 3). CCP and rheumatoid factor (RF) were detected in one patient not on CFTR modulator therapy (with US synovitis of PIP). Two patients on CFTR modulator therapy tested positive for RF. Another patient was seronegative but synovitis was confirmed by US. Of note, longer duration of CFTR modulator therapy was significantly associated with a lower number of tender joints (r = -0.410 p = 0.054), swollen joints (r = -0.400, p = 0.048) and a lower CRP (r = -0.509, p = 0.048) (Figure 1). The current cohort study confirms that musculoskeletal symptoms are frequent in adult CF patients. Self-reported myalgias were significantly associated with arthritis mainly involving small joints. Interestingly, longer duration of CFTR modulator therapy was associated with a decreased number of tender and swollen joints in line with the assumption that amelioration of mucosal airway inflammation may decrease the risk of developing CF arthropathy. [1]Janssen KMJ et al. Arthritis Res Ther 2015. doi: 10.1186/s13075-015-0690-6 [Display omitted] NIL. None Declared. Table 1Baseline characteristic of cystic fibrosis (CF) patients, PGA = Patient global assessment, RF = Rheumatoid factorsCFpatientsn = 25CF+Arthropathyn = 6CF- Arthropathyn = 19PAge (years), mean (±SD)26 ± 528 ± 725 ± 3NSBMI (kg/m2), mean (±SD)23 ± 424 ± 522 ± 3NSFemale sex, n (%)13/25 (52)3/6 (50)10/19 (53)NSCF disease characteristicsPGA (0-10) Tiredness, mean (±SD)2.6 ± 1.72.8 ± 1.52.2 ± 1.6NSProductive cough ejection > 1 Tablespoon, n (%)3/25 (12)2/6 (33)1/19 (5)0.038CFTR modulator n (%)22/25 (88)3/6 (50)0/19 (0)0.001Clinical joint characteristicsPGA (0-10) Pain, mean (±SD)1.9 ± 2.43.2 ± 0.90.8 ± 0.80.001Arthralgia, n (%)12/25 (48)5/6 (83)7/19 (37)0.047Myalgia, n (%)5/25 (20)4/6 (67)1/19 (5)0.001Swollen Joint, n (%)5/25 (20)5/6 (83)0/19 (0)<0.0001Tender Joint, n (%)6/25 (24)6/6 (100)0/19 (0)<0.0001Morning stiffness, n (%)6/25 (24)3/6 (50)3/19 (16)NSSqueeze test, n (%)2/25 (8)2/6 (33)0/19 (0)0.008ACPA, n (%)/RF, n (%)1/25 (4)/3/25 (12)1/6 (17)/3/6 (50)0/19 (0)/0/19 (0)NS/ 0.001Laboratory parametersESR (mm/h), mean (±SD)9 ± 1122 ± 145 ± 40.045CRP (mg/L), mean (±SD)4.2 ± 5.18.3 ± 3.42.8 ± 4.70.014

Background:An ongoing debate revolves around whether axial spondyloarthritis (axSpA) with psoriasis and psoriatic arthritis (PsA) with axial involvement (axPsA) constitute the same disease or separate entities. The discussion is intensified by the absence of a universally accepted definition for axPsA. With regards to biologic disease-modifying antirheumatic drugs (bDMARDs), both tumor necrosis factor and interleukin-17 inhibitors (TNFi and IL-17i, respectively) have proven effective in both axSpA and PsA. However, interleukin-23 inhibitors (IL-23i) have demonstrated efficacy in PsA but not in axSpA. Post-hoc analyses of randomized controlled trials (RCTs) of IL-23i in PsA suggest, however, that this drug class might also be efficacious in axPsA.Objectives:To compare the retention of TNFi, IL-17i and IL-23i in patients with axPsA in a large national observational cohort of PsA patients treated under real-life conditions.Methods:Patients diagnosed with PsA were included in this study if their treating rheumatologist confirmed the presence of axial involvement (based on their interpretation of clinical signs, symptoms, and imaging) in the online database of the national PsA registry at any time before the initiation of bDMARD treatment. Treatment with TNFi, IL-17i, and IL-23i was considered if started between 2015 and 2023, as all three modes of action were approved for the treatment of PsA during this period. Drug retention was investigated using mixed-effects Cox proportional hazards models adjusted for covariates, including age, sex, presence of enthesitis or peripheral arthritis, current smoking, obesity, degree of cutaneous psoriatic involvement (at least moderate-severe vs. ≤ mild-moderate), start of the treatment course (TC) 2019-2023 vs. 2015-2018, and the number of bDMARDs and targeted synthetic (ts-)DMARDs previously utilized. Sensitivity analyses were performed with additional adjustments for the level of C-reactive protein and co-medication with conventional synthetic (cs)DMARDs. The analyses accounted for the possibility that some patients might have been treated with several drugs of the same class, as well as with drugs of different classes.Results:A total of 952 TCs in 543 patients with axPsA met the inclusion criteria. Among these, 364 TCs had available information on covariates and were included in the adjusted analyses (219 TNFi, 97 IL-17i (84 secukinumab and 13 ixekizumab), and 48 IL-23i (33 ustekinumab and 15 guselkumab)). Patients were older and had a longer symptom duration at start of IL-17i and IL-23i TCs compared to TNFi (Table 1). While the distribution of patients with peripheral arthritis was similar between the groups, the proportion of patients with enthesitis was lower at the start of IL-23i. AxPsA patients starting IL-17i and IL-23i exhibited more severe skin disease, aligning with the established superior efficacy of these drugs for psoriatic skin disease compared to TNFi. Patients initiating IL-17i and IL-23i had experienced a higher number of previous bDMARD failures. The adjusted analysis revealed no evidence for a difference between drug discontinuation between IL-17i vs. TNFi and IL-23i vs. TNFi (HR 0.98, 95% CI 0.68-1.41; and HR 1.01, 95% CI 0.62-1.63, respectively) (Table 2). These results were confirmed after additional adjustment for CRP and co-medication with a csDMARD (HR 1.08, 95% 0.71-1.63 for IL-17i vs. TNFi and HR 0.98, 95% CI 0.56-1.69 for IL-23i vs. TNFi).Table 1. Patient characteristics at the start of individual treatment courses (N = 364) stratified by drug class: TNFi, IL-17i, and IL-23i, respectively.Table 2. Mixed-effects Cox proportional hazards models for analysis of drug discontinuation of a bDMARD in PsA patients with axial involvement. (Analysis performed in 364 treatment courses in 275 patients with 244 discontinuation events).Conclusion:While the profiles of axPsA patients treated with IL-17i and IL-23i differed from those treated with TNFi, our data do not demonstrate a significant difference in drug retention among the three drug classes after adjusting for potential confounding.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:Adrian Ciurea: None declared, Andrea Goetschi: None declared, Burkhard Moeller Speaking fees from Janssen, Novartis, Pfizer, Eli Lilly, Grant/Research support from Amgen, Michael J. Nissen Speaking fees from AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, Amgen, Consulting fees from AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, Research grant from Novartis, Pfizer, Kristina Buerki: None declared, René Braem: None declared, Michael Andor: None declared, Thomas Hügle Payments for lectures and presentations from Pfizer, Fresenius Kabi, AbbVie, Merck Sharp and Dohme, Galapagos, Eli Lilly and Novartis, Holds stock or stock options of Atreon SA and Vtuls, royalties from Curmed, Pariticapted on Advisory Boards for DETECTRA, Andrea Rubbert-Roth Honoraria for lectures from AbbVie, Janssen, Novartis and Pfizer, Consulting fees from AbbVie, Janssen and Pfizer, Support for attending meetings from Janssen, Pfizer, Diego Kyburz Honoraria for presentations from AbbVie, Eli Lilly, Payments for participation on advisory boards from AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, Roche, Research grant from AbbVie, support for attending meetings from Janssen and Eli Lilly, Sabine Adler: None declared, Oliver Distler: None declared, Almut Scherer Employed by Bristol-Myers-Squib in 2007-2008, Raphael Micheroli Honoraria for lectures or presentations from AbbVie, Eli Lilly, Janssen, Gilead, Pfizer.

Background:Polymyalgia Rheumatica (PMR) is a common inflammatory rheumatic condition in people aged ≥50 years with incidence peaking at 70–80 years. PMR is primarily treated with glucocorticoids (GC) with guideline recommended treatment duration of 36–48 weeks without a flare or 40–52 weeks with a single flare.[1] However, it is estimated that 77%, 51%, and 25% of PMR patients remain on GC at 1, 2, and 5 years, respectively.[2] Extended GC therapy can increase the risk of GC-related toxicity, particularly in this elderly population. Thus, early recognition of patients who may require GC treatment for >1 year will help identify patients at risk of GC toxicity who could benefit from GC sparing therapies. Few studies have evaluated factors that could be indicators of patients likely to require extended GC therapy.[3,4]Objectives:To identify characteristics at 6 months in new onset PMR patients associated with extended GC use beyond 1 year.Methods:This was an exploratory analysis of an inception cohort of PMR patients identified from fee-for-service Medicare claims from 10/01/2016 to 12/31/2020.[5] Patients included had no history of PMR or giant cell arteritis, were ≥50 years, had ≥1 inpatient or ≥2 outpatient claims for PMR (ICD-10-CM M35.3) ≥30 days and <365 days apart. They initiated GC (prednisone equivalent) 7.5–25 mg/day ≤30 days after 1st inpatient code or from 1st outpatient to ≤30 days after 2nd outpatient code, had GC dose ≥200 mg in first ≤30 days and ≥4 months continuous GC use. Continuous enrollment ≥1 year prior to first diagnosis date was required. Patients with other systemic rheumatic disease, active malignancy treatment, multiple sclerosis, solid organ transplant, or prescription for conventional synthetic immunomodulatory drugs [csIM (methotrexate [MTX], leflunomide, azathioprine)] or interleukin-6 receptor inhibitors, ≤1 year prior to first (inpatient) or second (outpatient) PMR diagnosis to 6 months after GC initiation (baseline period), were also excluded (GC cohort). A supplemental analysis evaluated patients who met other criteria and received a csIM ≤6 months from GC initiation (csIM cohort). The primary outcome was comparison of characteristics (demographic, clinical, and healthcare resource utilization) at 6 months between patients who were on GC vs. off GC (>60-day gap) at 1 year. Comorbidities were defined using diagnosis, procedure, or drug codes. Frailty was assessed by a validated claims-based frailty index[6] and defined using a published threshold.[7]Results:A total of 4,748 patients were included in the GC cohort and 318 in the csIM cohort. MTX was the most common csIM [200/318 (62.9%)]. Of patients in the GC cohort and csIM cohort, 3,038 (64.0%) and 183 (57.5%) were on GC at 1 year, respectively. In both GC and csIM cohorts, significantly more patients on GC vs. off GC at 1 year were on GC dose ≥5 mg at 6 months. Patients on GC vs. off GC at 1 year also had significantly higher cumulative GC use at 6 months in both cohorts (Table 1). In the GC cohort, demographic characteristics and presence of comorbidities or frailty at 6 months, were not associated with GC use at 1 year while in the csIM cohort, age, year GC was initiated, initial GC dose, and glaucoma were significantly associated with GC use at 1 year (Tables 1,2). A sensitivity analysis including patients who initiated MTX within 6 months found 55.5% (111/200) of patients were on GC at 1 year and MTX use was significantly associated with GC use at 1 year: fewer patients on GC vs. off GC at 1 year had received MTX within 6 months [111/3149 (3.5%) vs 89/1799 (4.9%); p=0.015].Conclusion:More than half of PMR patients remained on GC beyond 1 year. Evaluation of GC dose at 6 months may be useful to identify patients who may benefit from GC sparing therapy.REFERENCES:[1] Dejaco C et al. Arthritis Rheumatol 2015, 67:2569–80.[2] Floris A et al. Clin Rheumatol 2022, 41:19–31.[3] Perricone C et al. Clin Exp Med 2023, 23:3391–7.[4] Birra D et al. Clin Exp Rheum 2020, 38:436–41.[5] Curtis J, et al. Arthritis Rheumatol 2023, 75.[6] Kim DH et al. J Gerontol A Biol Sci Med Sci 2018, 73:980–7.[7] Halawa OA, et al, Ophthalmology 2023, 130: 646-54.Acknowledgements:This study was funded by Sanofi and Regeneron Pharmaceuticals, Inc. Medical writing support for this abstract was provided by Kavita Garg, PhD, CMPP, of Sanofi.Disclosure of Interests:Anisha B Dua Consultant: AbbVie, Amgen, Astra Zeneca, GSK, Sandoz, Sanofi, Andrea Rubbert-Roth Honoraria for consultation and lectures from AbbVie, BMS, Gilead, Lilly, Pfizer, Roche, Sanofi, UCB, Kerri Ford Employee of Sanofi and may hold stock and/or stock options in the company, Stefano Fiore Employee of Sanofi and may hold stock and/or stock options in the company, Lita Araujo Employee of Sanofi and may hold stock and/or stock options in the company, Timothy Beukelman Consultant: UCB, Fenglong Xie: None declared, Jeffrey R Curtis Consulting and research grants from AstraZeneca, Amgen, AbbVie, Bendcare, Genentech, GSK, Horizon, Janssen, Lilly, Novartis, Pfizer, Sanofi, Scipher, Setpoint, and UCB.

Objectives To confirm the effectiveness and safety of the interleukin 6-receptor antagonist tocilizumab in patients with rheumatoid arthritis (RA) in a setting close to real-life medical care in Germany. Methods A multicentre open-label phase IIIb study was undertaken. Patients with active RA with a 28-joint Disease Activity Score (DAS28) >3.2 despite previous disease-modifying antirheumatic drugs (DMARDs) were treated with tocilizumab 8 mg/kg every 4 weeks. The primary end point was the proportion of patients achieving LDAS ≤3.2 at week 24; secondary end points included American College of Rheumatology (ACR), European League Against Rheumatism (EULAR) or Clinical Disease Activity Index (CDAI) responses and decrease in acute phase. Analyses in subgroups such as rheumatoid factor (RF)-positive versus RF-negative patients and patients with an inadequate response to treatment with DMARDs (DMARD-IR) versus those with an inadequate response to tumour necrosis factor (TNF) antagonists (TNF antagonist-IR) were performed. Safety was assessed by adverse event documentation. Results 286 patients were treated and 83.6% completed the study. 41.6% had previously been treated with TNF antagonists. 57% of the intention-to-treat patients achieved the primary end point of LDAS, 47.6% achieved DAS remission <2.6 and a EULAR ‘good response’ was achieved by 54.9%; ACR50/70 response rates at week 24 were 50.7% and 33.9%, respectively. The mean±SD decrease in CDAI from baseline to week 24 was 71±29%. C reactive protein levels normalised rapidly within 1 week. Major improvements in fatigue, pain and morning stiffness were observed in the first 4 weeks and further improved until week 24. DAS28, EULAR and ACR responses at week 24 did not differ between RF-positive and RF-negative patients. TNF antagonist-naive patients responded better than patients who had previously failed on TNF antagonists. The safety profile of tocilizumab was comparable to that previously observed in the phase III trial programme. Serious infections were observed in 3.1% of patients. Conclusions Tocilizumab is highly effective in a setting close to real-life medical care with a rapid and sustained improvement in signs and symptoms of RA. A manageable safety profile was seen over the 24-week study period.