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BackgroundComplement activation is a hallmark of SLE pathophysiology. We previously found that iC3b/C3 ratios associated with active disease and clinically meaningful changes in SLE disease activity. Since SLE is more severe in nonwhite populations, we hypothesized that iC3b/C3 ratios would be a more sensitive marker of disease activity in nonwhite populations.ObjectivesWe examined the relationship of iC3b/C3 ratios between African-American (AA) and White subjects with classified SLE.Methods159 adult SLE patients treated at the Washington University Lupus Center were enrolled in this observational study. 83 patients with 3-7 study visits were used for this longitudinal analysis. C3 and C4 were measured by nephelometry; iC3b by a lateral flow assay using an investigational medical device. SLE disease activity was measured using the SLEDAI 2K Responder Index-50 instrument. Statistical analyses were performed using SAS v9.4. Multilevel regression models examined associations for SLE disease activity. Ordinal logistic regression models with generalized estimating equation modeling (GEE) examined associations for clinically meaningful changes since the outcome variable is ordinal. Odds ratios and 95% confidence intervals were estimated using Proc GLIMMIX and Proc GENMOD.ResultsiC3b/C3 ratios and C3 associated with active disease in AA and White SLE subjects, with the association of the iC3b/C3 ratio in AA was stronger (Figure 1). In addition, AA with SLE associated C4, ESR, and dsDNA with active disease, while Whites associated with CRP. In multiple regression analysis, iC3b/C3 ratios independently associated with active disease in both groups, although the effect was more pronounced in AA (AA: OR=1.48, 95% CI=1.21-1.82; Whites: OR=1.17, 95% CI=1.02-1.34). Furthermore, in univariate regression analysis, only the iC3b/C3 ratio in AA associated with clinically meaningful changes in disease activity.ConclusioniC3/C3 ratios better correlated with active disease in AA compared to Whites. Furthermore, iC3b/C3 ratios correlated with clinically meaningful changes in disease activity only in AA. These data suggest that complement activation in SLE is dependent on race.Reference[1] Kim et al, Arthritis Rheumatol, 71:420, 2019, doi: 10.1002/art.40747AcknowledgementsI have no acknowledgements to declare.This research was funded/supported by Kypha, Inc. and National Institutes of Health (NIH)/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) under Award Number R21AR069833. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.Disclosure of InterestsDeepali Sen: None declared, Vibeke Strand Consultant of: AbbVie, Amgen, Arena Pharmaceuticals, Aria Pharmaceuticals, AstraZeneca, Bayer, Bristol Myers Squibb, Bioventus, Boehringer Ingelheim, Celltrion, ChemoCentryx, EMD Serono, Endo, Equillium, Galapagos, Genentech/Roche, Gilead Sciences, GSK, Horizon, Ichnos Sciences, Inmedix, Janssen, Kiniksa Pharmaceuticals, Kypha, Lilly, Merck, MiMedx, Novartis, Pfizer, Regeneron, Rheos Medicines, R-Pharm US, Samsung, Sandoz, Sanofi, Scipher Medicine, Servier Pharmaceuticals, SetPoint Medical, Sorrento Therapeutics, Sun Pharma, UCB., Qiang Fu: None declared, Alfred Kim Speakers bureau: AstraZeneca, Aurinia, Exagen Diagnostics, GlaxoSmithKline, Consultant of: Alexion, ANI Pharmaceuticals, AstraZeneca, Aurinia, Exagen Diagnostics, GlaxoSmithKline, Kypha, Pfizer, Grant/research support from: GlaxoSmithKline.

BackgroundSLE patients present significant challenges in the management of their condition.ObjectivesThis study aims to uncover differences in physician perceptions and real-world treatment patterns and outcomes among moderate to severely active patients in the EU5 (France, Italy, Spain, Germany, and UK).Methods1,279 moderate-to-severe (M/S) adult SLE patient records were collected in collaboration with 289 EU5 rheumatologists via an online survey platform from November 2021 through January 2022.Results22% of moderate-to-severe EU5 SLE patients in the chart audit were receiving belimumab to treat their SLE. In half of those cases where patients were NOT on belimumab they were not considered good candidates for the therapy. The key reason for not initiating belimumab treatment being that patients were “well-controlled” on their current pharmacologic regimen.Closer inspection of these “well-controlled” patients (n=228) at the chart level revealed clinical aspects that highlight a potential gap in patient care:The majority of SLE patients in the “well-controlled” subset had moderately active disease, but over one-in-ten were classified with severe disease.On average, 40% of “well controlled” SLE patients had one or more flares over the past year.One-third of the “well controlled” patient subset suffers from at least one moderate-to-severe manifestation of their SLE, with musculoskeletal, dermatologic, and renal manifestations being most prevalent.29% of “well-controlled” patients have at least one moderate-to-severe symptom of their disease. These include pain/stiffness, fatigue, synovitis, malar rash, photosensitivity, edema, fever, and alopecia.Table 1.SLE Disease SeverityModerateSevere“Well-controlled” patients89%11%SLE Flares (past year)None1 flare2 flares3 flares“Well-controlled” patients60%30%8%2%Severe SLE ManifestationsHas at least one moderate-to-severe manifestation“Well-controlled” patients32%SLE ManifestationModerate-to-Severe Manifestation SeverityMusculoskeletal24%Dermatologic11%Renal6%Pulmonary5%Severe SymptomsHas at least one moderate-to-severe symptom“Well-controlled” patients29%SymptomModerate-to-Severe Symptom SeverityPain, stiffness19%Fatigue16%Synovitis7%Malar rash6%Photosensitivity6%Edema4%Further, one-third of “well controlled” SLE patients are on steroids, with 40% on a higher dose (>5mg/day) to control their disease. The mean overall dosage of the group was 9.4mg/day, a potentially harmful dosage particularly if used long term.Figure 1.ConclusionEU5 physicians’ perception of “well controlled” SLE may not align with some patients’ clinical reality. Use of belimumab or other advanced therapies [1] in these cases may lead to improved patient outcomes and less reliance on steroids, which are often associated with adverse effects, even at low doses [2].References[1]At the time of fielding, anifrolumab had not yet been approved for treatment of SLE in the EU5.[2]European Lupus Society: SLEuro Lupus White Book, 2022 (sleuro.org). “Timely administration of immunosuppressants, either biologics or non-biologics, should be performed for a better control of disease activity coupled with an early steroid sparing effect.”Acknowledgements:NIL.Disclosure of InterestsRyan Rex: None declared, Emily Hettel: None declared, Vibeke Strand Consultant of: AbbVie, Amgen, Aria, AstraZeneca, Bayer, Bioventus, Blackrock, BMS, Boehringer Ingelheim, Celltrion, Chemocentryx, Equillium, Gilead, Genentech/Roche, Glenmark, GSK, Horizon, Inmedix, Janssen, Kiniksa, Kypha, Lilly, Merck, MiMedx, Novartis, Pfizer, Priovant, Regeneron, Rheos, R-Pharma, Samsung, Sandoz, Sanofi, Scipher, Setpoint, Sorrento, Spherix, Tonix, Sawyer May: None declared.

BackgroundThe VOLTAIRE trials program compared safety, efficacy, and immunogenicity of biosimilar BI 695501 with adalimumab reference product (RP) for indications including moderate-severely active rheumatoid arthritis (RA), Crohn’s disease (CD), and chronic plaque psoriasis (PsO). Details of each active-comparator, randomized controlled trial (RCT) are published. [1,2,3]ObjectivesHere we compare immunogenicity across these indications and by patient sex.MethodsImmunogenicity was assessed at various timepoints by the proportion of patients with anti-drug antibodies (ADAs) and neutralising antibodies (nAbs), using acid dissociation followed by an electrochemiluminescence assay (ECL; MSD platform; Meso Scale Diagnostics LLC, USA).[4] Assay sensitivity was 50 ng/mL, and drug tolerance ≥30 μg/mL (free drug) at the low positive control level.ResultsData are presented in Table 1.Table 1.Immunogenicity dataVOLTAIRE-RAVOLTAIRE-CDVOLTAIRE-PsOBI 695501RPBI 695501RPBI 695501RPAntibody first detectableADABaselineBaselineBaselineWeek 4 aBaselineBaselinenAbBaselineBaselineWeek 4 aWeek 4 aBaselineBaselineADA titre at primary endpoint, mean (SD)54.1 (93.54)at wk 12163.2 (753.96)at wk 24353.5 (1816.96) at wk 12294.7 (1555.05) at wk 24647.9 (2176.14) at wk 417.5 (31.03) at wk 432.0 (1, 16384) at wk 16 b32.0 (1, 8192) at wk 16 bProportion of patients with antibodies (ADAs and nAbs) over timeADA positiveccBaseline3.4% (11/323)6.5% (21/321)4.3% (3/69)0% (0/74)10.7% (17/159)10.8% (17/158)Day 7 (Wk 1)5.7% (18/317)9.3% (29/311)Day 14 (Wk 2)10.1% (32/318)16.0% (51/318)Day 28 (Wk 4)20.1% (64/319)19.7% (62/315)20.6% (14/68) b5.5% (4/73) bDay 84 (Wk 12)32.4% (101/312)34.9% (106/304)Day 113 (Wk 16)68.2% (101/148)71.8% (107/149)Day 168 (Wk 24)43.2% (127/294)47.8% (144/301)nAb positiveccBaseline2.8% (9/323)5.0% (16/321)0% (0/69)0% (0/74)0.6% (1/159)1.9% (3/158)Day 7 (Wk 1)2.5% (8/317)3.9% (12/311)Day 14 (Wk 2)3.1% (10/318)8.2% (26/318)Day 28 (Wk 4)6.9% (22/319)7.3% (23/315)8.8% (6/68) a2.7% (2/73) aDay 84 (Wk 12)13.1% (41/312)16.8% (51/304)Day 113 (Wk 16)54.1% (80/148)55.7% (83/149)Day 168 (Wk 24)16.0% (47/294)20.6% (62/301)Proportion of patients with ADA antibodies by subgroupSexWk 12Male (13/53)24.5%Female (88/259)34.0%Wk 24Male (19/50)38.0%Female (110/246)44.7%Wk 12Male (18/47)38.3%Female (88/257)34.2%Wk 24Male (25/47)53.2%Female (119/254)46.9%Wk 4Male (8/37)21.6%Female (6/31)19.4%Wk 4Male (2/42)4.8%Female (2/31)6.5%Wk 16Male (65/93)69.9%Female (36/55)65.5%Wk 16Male (66/97)68.0%Female (41/52)78.8%a. Wk 4 = Day 29 in CD trial; b. Median (minimum, maximum); c. Reported by randomisation completed at baselineConclusionMinor differences in immunogenicity (ADAs, ADA titres and nAbs) between BI 695501 and adalimumab RP were observed across these 3 indications. The proportion of ADA- and nAb-positive patients increased from baseline in all 3 RCTs, and were similar in RA and CD RCTs, but rates were higher in PsO RCT. Subgroup analysis by patient sex showed the same trend. These differences may be partially explained by concomitant background therapy (MTX) in RA trial, stable doses of AZA, 6-MP or MTX in 36% of CD patients and the absence of background therapy in PsO RCT. Comparisons are limited by different visit schedules in the trials. Historical comparisons to RP data are complicated by recent differences in regulatory requirements for increased ADA assay sensitivity and stringency for biosimilar products than those originally used for the RP. Acid dissociation followed by the more sensitive ECL assay for detection of ADAs is not dependent on serum drug concentrations. In conclusion, these analyses confirm the biosimilarity of BI 695501 with the adalimumab RP across RA, CD, and PsO.References[1] Cohen SB, et al. Ann Rheum Dis. 2018;77:91-21.[2] Hanauer S, et al. Lancet Gastroenterol Hepatol. 2021;6:816-25.[3] Menter A, et al. Expert Opin Biol Ther. 2021;21:87-96.[4] Wynne C, et al. Expert Opin Inv Drugs 2016;25:1361-70.AcknowledgementsThe authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors. The authors received no direct compensation related to the development of the abstract. Writing support was provided by Debra Brocksmith, MB ChB, PhD, of Elevate Scientific Solutions (Envision Pharma Group), which was contracted and funded by Boehringer Ingelheim Pharmaceuticals, Inc. (BIPI). BIPI was given the opportunity to review the abstract for medical and scientific accuracy.Disclosure of InterestsVibeke Strand Consultant of: AbbVie, Amgen, Aria, AstraZeneca, Bayer, Bioventus, Blackrock, BMS, Boehringer Ingelheim, Celltrion, Chemocentryx, Equillium, Gilead, Genentech/Roche, Glenmark, GSK, Horizon, Inmedix, Janssen, Kiniksa, Kypha, Lilly, Merck, MiMedx, Novartis, Pfizer, Priovant, Regeneron, Rheos, R-Pharma, Samsung, Sandoz, Sanofi, Scipher, Setpoint, Sorrento, Spherix, and Tonix, Shaun Bender Employee of: Boehringer Ingelheim Pharmaceuticals, Inc. (previous employment), Dorothy McCabe Employee of: Boehringer Ingelheim Pharmaceuticals, Inc.

The best imaging target for remission is demonstration that no progression of structural damage has occurred. Radiographs are able only to show inhibition of structural damage over a 6 to 12 month period, and they do not demonstrate erosions as early after onset of clinical manifestations as do Magnetic Resonance Imaging [MRI] or Power Doppler Ultrasonography [PDUS]. Likely reflecting erosions and JSN already destined to happen, future radiographic progression is best determined by damage at baseline. Radiographs remain the “gold standard” by which inhibition of structural damage is demonstrated – from a regulatory point of view, this definition, also clinically meaningful, is “no progression”: either change ≤0 in vander Heijde modified Total Sharp Scores [vdHS] or ≤0.5 to account for variability between ≥2 readers. Clinically meaningful changes in vdHS scores have been variously described to be ≥3, ≥5 points or >smallest detectable change [SDC] over 12 or 24 months. However such cut- offs have little meaning unless viewed in the context of baseline damage [and thus the individual patient], and more frequently than not SDC values well exceed observed mean changes over time. PDUS visualizes synovitis and erosions; MRI synovitis, bone edema [BE or osteitis] and erosions – both better visualize structural damage early in disease as well as its progression. Prospectively we know that both imaging methodologies demonstrate changes ascribed to inflammation that ultimately result in damage observed by x ray. Most would surmise that synovitis by PDUS and/or BE by MRI at 3 or 6 months will be reflected by progression in radiographic vdHS scores at 12 months. Although not fully prospectively validated, MRI hopefully will soon become the more sensitive standard for assessing progression of structural damage in randomized controlled trials [RCTs]. PDUS lends itself more easily to daily clinical practice but has been successfully utilized in RCTs, based on standardization of techniques and acquisition of imaging. The opposite process is less clear. Although healing of erosions has been demonstrated longitudinally by x ray, resolution of erosions evident on MRI appears to be less reversible. Although PDUS can demonstrate synovitis and erosions, it is not able to show BE, and gray scale US has evidenced abnormalities even in healthy volunteers. To return to the target of “remission” – do we need a separate definition based on imaging? or to add an imaging component to our remission criteria? In a majority of RCTs, a large percentage of patients considered in remission by stringent definitions such as SDAI, CDAI and Boolean do not demonstrate progression in vdHS scores and longitudinal observational studies [LOS] have shown similarly that few have persistent synovitis/erosions by PDUS or BE/erosions by MRI. This is particularly true if there are no swollen joints or elevated CRP. The question remains, are there still patients with “sub-clinical” synovitis/inflammation that can be detected by these more sensitive imaging techniques who will not do well over time or tolerate tapering of therapy? Here again definitions of clinically meaningful progression, or the lack thereof, based on PDUS and MRI are still to be determined. Thus the importance of the planned RCTs examining attainment of remission based on clinical definitions with/without PDUS: ARCTIC and TURA, or with/without MRI: IMAGINE. Until these results are known it is best that we rely upon strict clinical definitions of remission, particularly in early disease, knowing that, if maintained over ≥12 months these will result in little progression of structural damage. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.6234

Background Secukinumab has demonstrated sustained improvement in the signs and symptoms of psoriatic arthritis (PsA) over 2 years in the FUTURE 2 study (NCT01752634). This post hoc analysis assessed the ability of secukinumab to achieve Psoriatic Arthritis Disease Activity Score (PASDAS)-based remission or low disease activity (LDA) through 2 years among patients with PsA in the FUTURE 2 study. Methods PASDAS (cut-off scores: remission ≤ 1.9; LDA > 1.9 and < 3.2; Moderate Disease Activity ≥ 3.2 and < 5.4; and high disease activity [HDA] ≥ 5.4) was assessed in the overall population (tumour necrosis factor inhibitor [TNFi]-naïve and TNFi-experienced), in patients stratified by prior TNFi use and by disease duration at weeks 16, 52 and 104. The impact of secukinumab on individual PASDAS core components and on the relationship between PASDAS states and patient-reported outcomes (PROs), including physical function, health-related quality of life (HRQoL) and work productivity, were also assessed. Data for the approved doses of secukinumab (300 and 150 mg) are reported. PASDAS scores and core components were reported as observed, and PROs were analysed using mixed models for repeated measures. Results In the overall population, PASDAS remission and LDA were achieved in 15.6% and 22.9%, respectively, of patients treated with secukinumab 300 mg and in 15.2% and 19.2%, respectively, in the secukinumab 150 mg group versus 2.3% and 13.8%, respectively, with placebo at week 16. In the TNFi-naïve group, a higher proportion of patients achieved remission + LDA at week 16 with secukinumab 300 and 150 mg (46.2% and 42.9%, respectively) versus placebo (17.5%), with corresponding responses in TNFi-experienced patients being 22.6% and 19.4% versus 13.3%. Remission/LDA responses with secukinumab were sustained through 2 years. Patients achieving remission/LDA reported greater improvements in PROs than patients in HDA through 2 years. Conclusions Secukinumab-treated patients achieved higher PASDAS-defined remissions or LDA compared with placebo at week 16, which were sustained through 2 years. Remission/LDA was achieved by both TNFi-naïve and TNFi-experienced patients treated with secukinumab, with higher rates in TNFi-naïve patients. Secukinumab-treated patients achieving remission/LDA reported significantly greater improvements in PROs, including physical function and different dimensions of health-related quality of life and work, than patients in HDA. Trial registration ClinicalTrials.gov, NCT01752634 . Registered on December 19, 2012. EUDRACT, 2012-004439-22 . Registered on December 12, 2012.

Objective:To better understand the impact of gout on functional status, health-related quality of life (HRQoL), mortality and healthcare utilisation in US veterans.Methods:All veterans seen in Veterans Integrated Service Network-13 from 1 October 1996 to 31 March 1998 received mailed surveys asking about demographic characteristics; performance of activities of daily living and HRQoL by Short Form-36 (SF-36) for Veterans. Administrative data included demographics; inpatient/outpatient healthcare utilisation; ICD-9 codes for gout, medical comorbidities and arthritis excluding gout—“arthritic comorbidity” and 1-year mortality. Multivariable estimates compared results between veterans with/without gout using least means squared.Results:Subjects with gout were significantly older, retired, not married, current non-smokers, with more comorbidities. Multivariable-adjusted bodily pain was somewhat worse (49.7 vs 47.1, p<0.01) and mental health (66.7 vs 68.6, p<0.01) domain scores somewhat better in patients with gout, both differences significant but not clinically meaningful (less than threshold of 5–10 points); other SF-36 domain and summary scores and functional limitations were similar. Medical or arthritic comorbidities predicted clinically/statistically lower adjusted scores in all SF-36 domains and physical domains (physical component summary), respectively. Patients with gout had significantly more annual primary care visits (3.5 vs 2.7, p<0.001) and admissions to hospital (18.3% vs 15.1%, p<0.01), fewer mental health visits (10.1% vs 13.7%, p<0.01) and similar mortality (2.6% vs 2.2%, p = 0.23).Conclusions:Gout is independently associated with higher medical and arthritic comorbidity, primary care and inpatient utilisation. Poorer HRQoL, functional limitation and higher mortality noted in univariate analyses in patients with gout were attributable to higher comorbidity and sociodemographic characteristics.

Background:Certolizumab pegol is a PEGylated tumour necrosis factor inhibitor.Objective:To evaluate the efficacy and safety of certolizumab pegol versus placebo, plus methotrexate (MTX), in patients with active rheumatoid arthritis (RA).Methods:An international, multicentre, phase 3, randomised, double-blind, placebo-controlled study in active adult-onset RA. Patients (n = 619) were randomised 2:2:1 to subcutaneous certolizumab pegol (liquid formulation) 400 mg at weeks 0, 2 and 4 followed by 200 mg or 400 mg plus MTX, or placebo plus MTX, every 2 weeks for 24 weeks. The primary end point was ACR20 response at week 24. Secondary end points included ACR50 and ACR70 responses, change from baseline in modified Total Sharp Score, ACR core set variables and physical function.Results:Significantly more patients in the certolizumab pegol 200 mg and 400 mg groups achieved an ACR20 response versus placebo (p⩽0.001); rates were 57.3%, 57.6% and 8.7%, respectively. Certolizumab pegol 200 and 400 mg also significantly inhibited radiographic progression; mean changes from baseline in mTSS at week 24 were 0.2 and −0.4, respectively, versus 1.2 for placebo (rank analysis p⩽0.01). Certolizumab pegol-treated patients reported rapid and significant improvements in physical function versus placebo; mean changes from baseline in HAQ-DI at week 24 were −0.50 and −0.50, respectively, versus −0.14 for placebo (p⩽0.001). Most adverse events were mild or moderate, with low incidence of withdrawals due to adverse events. Five patients developed tuberculosis.Conclusion:Certolizumab pegol plus MTX was more efficacious than placebo plus MTX, rapidly and significantly improving signs and symptoms of RA and physical function and inhibiting radiographic progression.Trial registration number:NCT00175877

Background:Tumour necrosis factor α (TNFα) is a proinflammatory cytokine involved in the pathogenesis of rheumatoid arthritis (RA). Treatment with TNFα inhibitors reduces disease activity and improves outcomes for patients with RA. This study evaluated the efficacy and safety of certolizumab pegol 400 mg, a novel, poly-(ethylene glycol) (PEG)ylated, Fc-free TNFα inhibitor, as monotherapy in patients with active RA.Methods:In this 24-week, multicentre, randomised, double-blind, placebo-controlled study, 220 patients previously failing ⩾1 disease-modifying antirheumatic drug (DMARD) were randomised 1:1 to receive subcutaneous certolizumab pegol 400 mg (n = 111) or placebo (n = 109) every 4 weeks. The primary endpoint was 20% improvement according to the American College of Rheumatology criteria (ACR20) at week 24. Secondary endpoints included ACR50/70 response, ACR component scores, 28-joint Disease Activity Score Erythrocyte Sedimentation Rate 3 (DAS28(ESR)3), patient-reported outcomes (including physical function, health-related quality of life (HRQoL), pain and fatigue) and safety.Results:At week 24, the ACR20 response rates were 45.5% for certolizumab pegol 400 mg every 4 weeks vs 9.3% for placebo (p<0.001). Differences for certolizumab pegol vs placebo in the ACR20 response were statistically significant as early as week 1 through to week 24 (p<0.001). Significant improvements in ACR50, ACR components, DAS28(ESR)3 and all patient-reported outcomes were also observed early with certolizumab pegol and were sustained throughout the study. Most adverse events were mild or moderate and no deaths or cases of tuberculosis were reported.Conclusions:Treatment with certolizumab pegol 400 mg monotherapy every 4 weeks effectively reduced the signs and symptoms of active RA in patients previously failing ⩾1 DMARD compared with placebo, and demonstrated an acceptable safety profile.Trial registration number:NCT00548834.

Background:Patients with systemic lupus erythematosus (SLE) experience poor health-related quality of life (HRQoL), even despite attaining responses by the SLE Responder Index (SRI)-4. [1]Objectives:We herein aimed to determine the prevalence of poor HRQoL in SLE patients who had attained low disease activity (LDA) or remission and sustained LDA or sustained remission after a 52-week therapeutic intervention in a clinical trial setting.Methods:A post-hoc analysis was conducted using data from four trials: BLISS-52, BLISS-76, BLISS-SC, and EMBRACE. We defined LDA according to the Lupus LDA State (LLDAS) criteria, i.e., SLEDAI-2K ≤4 excluding major organ activity or fever or new activity since the previous assessment, Physician Global Assessment (PGA) ≤1 (scale 0–3), and prednisone ≤7.5 mg/day. We defined remission according to the Definitions of Remission in SLE (DORIS) criteria i.e., clinical (c)SLEDAI-2K=0, PGA <0.5, and prednisone ≤5 mg/day. Sustained LLDAS/remission were defined as persistent LLDAS/remission for at least two visits, four weeks apart, maintained through week 52. Poor HRQoL was defined as Short Form-36 (SF-36) physical/mental component summary (PCS/MCS) and domain scores ≤ the normative fifth percentile, i.e., the worst 5% of scores reported from US population-based age- and sex-matched individuals, Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F) scores <30, and responses of “some/moderate problems” or “extreme/major problems” in each one of the five EQ-5D dimensions of the three-level version of EQ-5D (EQ-5D-3L).Results:Of 480, 239, 363, and 177 patients who attained LLDAS, DORIS remission, sustained LLDAS, and sustained DORIS remission at week 52, respectively, 16%, 14%, 15%, and 9% reported poor SF-36 PCS and 12%, 12%, 13%, and 14% reported poor SF-36 MCS scores, respectively. The greatest percentages were reported in the physical functioning domain (23–26%), followed by the general health domain (16–26%), while 19–26% reported FACIT-F scores ≤30. Lastly, pain/discomfort was the EQ-5D dimension that yielded the greatest frequencies of poor experience (28–29%) (Figure 1).Conclusion:Despite attainment of LLDAS or remission, substantial proportions of SLE patients experience poor HRQoL, indicating that current LDA and remission definitions fail to capture important aspects of patients’ well-being.REFERENCES:[1] Gomez A, et al. Adverse Health-Related Quality of Life Outcome Despite Adequate Clinical Response to Treatment in Systemic Lupus Erythematosus. Front Med (Lausanne). 2021 Apr 16;8:651249.Figure 1.Poor HRQoL despite (sustained) LLDAS or DORIS remission. Bars (A–B) and radar charts (C–D) depicting proportions of patients who reported poor HRQoL among patients who attained LLDAS (in dark pink), DORIS remission (in dark blue), sustained LLDAS (in dark pink), and sustained DORIS remission (in dark blue).Acknowledgements:NIL.Disclosure of Interests:Ioannis Parodis I have received research funding and/or honoraria from Amgen, AstraZeneca, Aurinia, Bristol Myers Squibb (BMS), Elli Lilly, Gilead, GlaxoSmithKline (GSK), Janssen, Novartis, Otsuka, and Roche. MN has received research grant support from Janssen and Boehringer Ingelheim; received honoraria from Janssen, GSK, AstraZeneca, Pfizer, and Boehringer Ingelheim. AL reports employment with BMS outside the submitted work., Julius Lindblom: None declared, Nursen Çetrez: None declared, Leonardo Palazzo: None declared, Henri Ala: None declared, Mandana Nikpour: None declared, Adrian Levitsky: None declared, Vibeke Strand I have received consulting fees from AbbVie, Alpine, Alumis, Amgen, Aria, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Celltrion, Ermium, Genentech/Roche, GSK, Horizon, Inmedix, Janssen, Kiniksa, Lilly, Merck, MiMedx, Novartis, Omeros, Pfizer, RAPT, Regeneron, R-Pharm, Samsung, Sandoz, Sanofi, Scipher, Setpoint, Sorrento, Spherix, Tonix, and Urica.

Background Interleukin 6 (IL-6) plays a key role in the inflammatory cascade in rheumatoid arthritis. BMS945429 is a humanised, monoclonal antibody that potently binds IL-6. Objective To conduct aphase II study to determine the efficacy and safety of BMS945429 in patients with active rheumatoid arthritis and an inadequate response to methotrexate. Methods Patients were randomised 1:1:1:1 to BMS945429 (80, 160 or 320 mg; administered intravenously) or placebo plus methotrexate during this 16-week, double-blind trial. The primary efficacy end point was the proportion of patients with a 20% improvement in American College of Rheumatology responses (ACR20) at week 12. Additional end points included ACR50 and ACR70 responses and 28-joint Disease Activity Scores (DAS28). Results Of 127 randomised and treated patients, 116 completed the trial. ACR20 responders at week 12 were 81% (80 mg; p<0.0001 vs placebo), 71% (160 mg; p=0.0005 vs placebo), 82% (320 mg; p<0.0001 vs placebo) and 27% (placebo), respectively. By week 16, 14% (80 mg), 28% (160 mg) and 44% (320 mg) of BMS945429 patients were in DAS28 remission (DAS28 score <2.6). Statistically significant and clinically meaningful improvements in health-related quality of life (HRQoL) were reported in all active treatment groups. Administration of BMS945429 was associated with increases in liver enzymes and in serum cholesterol. There were no serious infections, infusion reactions or apparent immunogenicity. Conclusions In this phase II study, BMS945429 was associated with rapid and significant improvements in disease activity and HRQoL in patients with active rheumatoid arthritis and an inadequate response to methotrexate.