DAS28-CRP Remission Research Articles

Fibroblast-like synoviocyte targeting antibodies are associated with failure to reach early and sustained remission or low disease activity after first-line therapy in rheumatoid arthritis

ObjectiveTo discover antibody biomarkers that can predict a lack of response to first-line therapy in rheumatoid arthritis (RA) patients.MethodsTwo RA cDNA phage display libraries were screened for novel antibodies in baseline RA sera from the Care in early RA (CareRA) trial, differentiating between patients who did or did not reach remission after first-line therapy (n=20 each). Antibody reactivity to identified University Hasselt (UH)-RA antigens was validated in baseline samples from 136 additional CareRA participants. The novel antibodies’ potential to predict failure to reach remission or low disease activity (LDA), according to the Disease Activity Score 28-joint C-reactive protein/erythrocyte sedimentation rate (DAS28CRP/ESR) and Clinical/Simplified Disease Activity Index (CDAI/SDAI), was studied by multivariate analyses. The presence of the antibody targets in RA synovial tissue and the fibroblast-like synoviocyte (FLS) cell line SW982 was determined by immunofluorescence.ResultsWe identified antibodies to 41 novel antigens. Antibodies against any of three antigens, UH-RA.305/318/329, discriminated between RA patients not reaching week (w)8 DAS28CRP remission and those that did (36% vs 13%,p=0.0031). In all patients, anti-UH-RA.305/318/329 antibody reactivity was associated with failure to reach week 8 DAS28CRP and DAS28ESR remission (OR 3.63,p=0.0031; OR 2.92,p=0.016; respectively), SDAI/CDAI sustained remission (OR 5.59,p=0.039 for both) and DAS28CRP and DAS28ESR sustained LDA (OR 3.7,p=0.009; OR 2.76,p=0.042; respectively). In rheumatoid factor/anti-citrullinated protein antibody (RF/ACPA) seronegative patients, these antibodies were strongly associated with failure to achieve week 8 DAS28CRP remission (OR 17.3,p=0.0029). Anti-UH-RA.305/329 antibodies were shown to target FLS in RA synovial tissue and SW982 cells.ConclusionWe identified three antibody biomarkers that are associated with failure to achieve remission/LDA after first-line RA therapy.

Efficacy and Safety of Levilimab in Combination with Methotrexate in Patients with Active Rheumatoid Arthritis: 56-Week Results of Phase III Randomized Double-Blind Placebo-Controlled Trial SOLAR.

. To evaluate the efficacy and safety of levilimab in combination with methotrexate (MTX) in subjects with MTX resistant active RA. : The study was conducted at 21 clinical sites in Russia and Belarus. All randomized subjects have completed the study between November 2019 and October 2021. Adult subjects (154) aged ≥18years with confirmed diagnosis of RA1 were randomly assigned (2 : 1) to receive either levilimab (162 mg, SC, QW) + MTX (n = 102) or placebo + MTX (n = 52). After W24 of the study all subjects continued toreceive open label levilimab. Subjects who have achieved DAS28-CRP ≤ 2.6 at W24 were switched to maintenance (Q2W) regimen of levilimab at W28 (LVL QW/Q2W and PBO/LVL Q2W arms). Those with DAS28-CRP > 2.6 at W28 continued with QW regimen (LVL QW and PBO/LVL QW arm). The PBO/LVL Q2W arm contained only one subject, thus not included in the analysis. The efficacy analysis was performed in a population of all randomized subjects. Those with missing data due to study discontinuation or rescue therapy prescription were considered non-responders. Otherwise, the analysis was performed on complete cases. Safety was assessed through monitoring of adverse events (AEs) in a population of those, who received at least on dose of LVL (n = 152). : Better response to treatment was observed in LVL QW/Q2W as it composed of those who reach DAS28-CRP ≤ 2.6 at W24. At this time point 15/27 (55.6%) of them achieved ACR70; 23/27 (85.2%) achieved DAS28-CRP remission (<2.6) and 7/27 (25.9%) achieved ACR/EULAR2011 remission of RA. After switching to LVL Q2W, rates of ACR70 and DAS28-CRP<2.6 did not significantly changed until W52: 17/27 (63.0%) and 21/27 (77.8%), respectively, yet the proportion of subject with ACR/EULAR 2011 remission further increased and reached 12/27 (44.4%). LVL QW arm was diminished by subjects who achieved high response to treatment at W24 and composed LVL QW/Q2W arm. Thus, ACR70, and remissions rate in this arm was close to zero at W24. However, continuation of LVL QW in those who not achieved DAS28-CRP ≤ 2.6 at W24 induced ACR70 response in 37/75 (36.0%), DAS28-CRP remission in 35/75 (46.7%) and ACR/EULAR 2011 remission in 8/75 (10.7%) at W52. The most common adverse events (reported in ≥5% of subjects) were blood cholesterol increase (30.3%), ALT increase (23.0%), lymphocyte count decrease (17.1%), ANC decrease (16.4%), blood triglycerides increase (13.8%), bilirubin increase (11.2%), AST increase (9.9%), WBC decrease (9.9%), IGRA with Mycobacterium tuberculosis antigen positive (7.2%), and injection site reactions (5.9%). No deaths occurred. : Open label period confirmed the lasting efficacy and safety of levilimab in combination with MTX in subjects with MTX resistant active RA and suggested the possibility of switching to levilimab maintenance regimen (once every 2 weeks) (Q2W) in those who achieved remission of RA at week 24.

Impact of blue-collar vs. white-collar occupations on disease burden in psoriatic arthritis patients: A Swiss clinical quality management in rheumatic diseases cohort study

Biomechanical stress may exacerbate inflammation in psoriatic arthritis (PsA). This study aimed to investigate disease activity, work disability, and drug response/retention rates in PsA patients among two different occupation’s types: blue-collar workers (BCol) with manual labor versus white-collar workers (WCol) with sedentary occupations. PsA patients registered in the Swiss cohort (SCQM) were classified as BCol or WCol workers and assessed at the initiation of a biologic or targeted synthetic disease-modifying anti-rheumatic drug (b-/tsDMARD). We compared the baseline characteristics at treatment start and the DAS28-CRP for the 1-year remission. Treatment retention was investigated using Kaplan–Meier curves and Cox regression analysis. Multivariable models were adjusted for potential confounders. Of 564 patients, 29% were BCol, and 71% were WCol workers. Baseline disease activity was comparable between both groups. BCol workers were predominantly male (79.8%) and more work disabled at baseline (84.0% vs. 27.9%; p < 0.01). One hundred seventy-four treatment courses (TCs) of 165 PsA patients were included for longitudinal analysis. Occupation did not significantly influence the achievement of DAS28-CRP remission at 1 year. Kaplan–Meier analysis (n = 671) indicated longer retention for BCol workers (mean retention duration: 3.15 years vs. 2.15 years, (p = 0.006). However, adjusted Cox regression analysis did not corroborate these findings. This study indicates that physically demanding occupations correlate with increased rates of work disability among PsA patients, while treatment response seems to be unaffected by the patients’ occupation type. Additional research is required to thoroughly comprehend the relationship between physical workload, disease activity, and treatment outcomes.Key Points• This study indicates that physically demanding occupations correlate with increased rates of work disability among PsA patients.• The treatment response among of PsA patients seems unaffected by the patients’ occupation type.

P112 The Impact of Filgotinib on Disease Activity Outcomes With Concomitant Pain Control in the Phase 3 FINCH Studies

Abstract Background/Aims Patients with rheumatoid arthritis (RA) often experience substantial pain despite treatment, and consider pain control an important treatment outcome. This post-hoc analysis of the FINCH studies assessed specific effects of filgotinib (FIL) on pain and its relationship with efficacy in patients with RA. Methods FINCH 1-3 (NCT02889796, NCT02873936, NCT02886728) were Phase 3, randomized, double-blind trials of FIL 100 mg and 200 mg (FIL100/200). For each treatment group, patients reported pain on a 100-mm visual analog scale (VAS). VAS pain ≤20 mm indicated health status was not negatively affected by pain; ≤10 mm reflected limited to no pain. Time to first VAS pain ≤10 mm was assessed. The duration of the study period during which VAS pain was ≤20 mm or ≤ 10 mm and the proportion of patients who achieved remission at Week 24 was evaluated. Of patients who achieved DAS28-CRP or CDAI remission, the proportion who also reported VAS pain ≤20 mm or ≤ 10 mm was determined. Results In FINCH 1, there was a higher probability of achieving VAS pain ≤10 mm with FIL200, vs ADA + MTX or PBO + MTX; responses were better or comparable with FIL100 vs other treatments. Similar findings were seen in FINCH 2 and 3. In FINCH 1, the time during which VAS pain score was ≤20 mm or ≤ 10 mm was greatest in the FIL200 group (Table). The duration of time under each pain threshold was greater in each FIL group vs PBO in FINCH 2 (Table) and in each FIL group vs MTX in FINCH 3. The proportion of patients who achieved VAS pain ≤20 mm and ≤10 mm in addition to DAS28-CRP remission was 35.8% and 26.3%, respectively, in the FIL200 + MTX group, vs 24.6% and 17.2% in the ADA + MTX group. Findings were similar when CDAI remission was assessed for FINCH 1 and 2. Conclusion Across the studies, duration of threshold pain responses achieved over the observation periods was greater with FIL vs comparators. These findings suggest that JAK1 inhibition may offer potential added value with respect to patient-reported pain as well as treat-to-target goals. Disclosure P.C. Taylor: Consultancies; AbbVie, Biogen, Eli Lilly, Fersenius Kabi, Galapagos, Gilead, GSK, Janssen, Nordic Pharma, Sanofi, UCB. Grants/research support; P.T. has received funding for research from Galapagos. A. Kavanaugh: Consultancies; AbbVie, Amgen, BMS, Janssen, Novartis, Pfizer, UCB. P. Nash: Honoraria; AbbVie, BMS, Celgene, Eli Lilly, Galapagos, GSK, Janssen, Novartis, Pfizer. Grants/research support; AbbVie, BMS, Celgene, Eli Lilly, Galapagos, GSK, Janssen, Novartis, Pfizer. J. Pope: Consultancies; AbbVie. G. Pongratz: Consultancies; AbbVie, Boehringer Ingelheim, Galapagos, Eli Lilly, Pfizer, Roche. Honoraria; AbbVie, Boehringer Ingelheim, Eli Lilly, Pfizer, Roche, Sanofi. B. Fautrel: Consultancies; AbbVie, BMS, Chugai, Fersenius Kabi, Galapagos, Eli Lilly, Medac, Nordic Pharma, Novartis, Pfizer, Sobi, UCB. Grants/research support; AbbVie, Eli Lilly, Pfizer. R. Alten: Consultancies; AbbVie, Amgen, Biogen, BMS, Celltrion, Gilead, Janssen, Eli Lilly, Medac, MSD, Mylan, Novartis, Pfizer, Roche, Sandoz, Sanofi, UCB, Viatris. Honoraria; AbbVie, Amgen, Biogen, BMS, Celltrion, Gilead, Janssen, Eli Lilly, Medac, MSD, Mylan, Novartis, Pfizer, Roche, Sandoz, Sanofi, UCB, Viatris. K. Hasegawa: Shareholder/stock ownership; Gilead. Other; Employee of Gilead. S. Rao: Other; Employee of Gilead. D. De Vries: Shareholder/stock ownership; Galapagos. Other; Employee of Galapagos. P. Stiers: Shareholder/stock ownership; Galapagos. Other; Employee of Galapagos. C. Watson: Shareholder/stock ownership; Galapagos. Other; Employee of Galapagos. R. Westhovens: Consultancies; Celltrion, Galapagos, Gilead. Honoraria; Celltrion, Galapagos, Gilead.

P123 Safety and efficacy of filgotinib, an update from the DARWIN 3 phase 2 long-term extension with a maximum of 8.2 years of exposure

Abstract Background/Aims DARWIN 3 (NCT02065700) is a long-term extension (LTE) study assessing the safety and efficacy of filgotinib (FIL) in patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX). In the DARWIN 1 (NCT01888874) and DARWIN 2 (NCT01894516) parent studies, patients received FIL in combination with MTX or FIL monotherapy, respectively. To provide an update on the safety and efficacy of FIL 200 mg (FIL200) in patients with RA, with or without MTX, with a maximum of 8.2 years of exposure. Methods Patients completing the DARWIN 1 and DARWIN 2 phase 2 studies could enter DARWIN 3, receiving FIL200[PE1] +/-MTX. The proportion of patients experiencing treatment-emergent adverse events (TEAEs) were reported, comprising data from both the parent and LTE studies. Efficacy was assessed from LTE baseline using the American College of Rheumatology (ACR) 20/50/70 criteria and DAS28-CRP, up to 264 weeks. Low disease activity and remission were defined as DAS28-CRP ≤3.2 and &amp;lt;2.6, respectively. Results In total, 739 patients were enrolled in DARWIN 3. In the FIL + MTX vs FIL monotherapy groups, TEAEs were reported for 90.9% and 92.1% of patients, respectively (Table). The most common TEAE was infection. In both treatment groups, eight patients had a TEAE leading to death (1.6% and 3.3%, respectively). Exposure-adjusted incidence rates, censored at time of first event for major adverse cardiovascular event, venous thromboembolism, herpes zoster, infections, serious infections, non-melanoma skin cancer (NMSC), malignancies excluding NMSC, gastrointestinal perforations and TEAEs leading to death, will be reported. Through five years, ACR20/50/70 responses were maintained in 86.3%/66.7%/50.7% of the FIL + MTX group and 90.8%/74.8%/51.4% of the FIL monotherapy group, respectively (observed data). DAS28-CRP low disease activity and remission rates (non-responder imputation) at DARWIN 3 baseline were 46.1%/40.1% (FIL + MTX) and 29.6%/24.8% (FIL monotherapy). At Week 264, the proportion of patients achieving low disease activity and remission were 34.0%/34.3% (FIL + MTX) and 27.0%/24.8% (FIL monotherapy). Conclusion With a maximum of 8.2 years of exposure in patients with RA, the FIL safety profile is similar between the background MTX and monotherapy treatment arms. Both arms show sustained efficacy over time. Disclosure P. Emery: Consultancies; Consultant of: AbbVie, AstraZeneca, BMS, Boehringer-Ingelheim, Galapagos, Gilead, Lilly, Novartis, Pfizer, Roche, and Samsung. Member of speakers’ bureau; y Speakers bureau: AbbVie, AstraZeneca, BMS, Boehringer-Ingelheim, Galapagos, Gilead, Lilly, Novartis, Pfizer, and Samsung. Grants/research support; Grant/research support from: AbbVie, BMS, Lilly, Novartis, Pfizer, Roche, and Samsung. R. Westhovens: Consultancies; Celltrion, Galapagos, and Gilead,. Member of speakers’ bureau; Celltrion, Galapagos, and Gilead. R.H.E. Alten: Consultancies; AbbVie, Amgen, Biogen, BMS, Celltrion, Gilead, Janssen, Lilly, Medac, MSD, Mylan, Novartis, Pfizer, Roche, Sandoz, SanofiGenzyme, UCB, and VIATRIS. L. Dagna: Consultancies; AbbVie, Amgen, AstraZeneca, Biogen, Boehringer-Ingelheim, BMS, Celltrion, Eli Lilly &amp; Company, Galapagos, GlaxoSmithKline, Janssen, Kiniksa Pharmaceuticals, Novartis, Pfizer, Roche, Sanofi-Genzyme,. Grants/research support; AbbVie, BMS, Celgene, GlaxoSmithKline, Janssen, Kiniksa, Merck Sharp &amp; Dohme, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI,. A. Kavanaugh: Consultancies; Amgen, AbbVie, BMS, Pfizer, UCB, Janssen, Novartis, and Pfizer. K.L. Winthrop: Consultancies; AbbVie, AstraZeneca, BMS, Eli Lilly &amp; Company, Galapagos, Gilead, GlaxoSmithKline, Novartis, Pfizer, Regeneron, Roche, Sanofi, and UCB. Grants/research support; BMS and Pfizer. J. Barry: Corporate appointments; Galapagos. Shareholder/stock ownership; Galapagos. R. Besuyen: Corporate appointments; Galapagos. Shareholder/stock ownership; Galapagos. C. Corallo: Corporate appointments; Galapagos. Shareholder/stock ownership; Galapagos. C. Watson: Corporate appointments; Galapagos. Shareholder/stock ownership; Galapagos. N. Martin: Consultancies; Galapagos. M. Genovese: Corporate appointments; Gilead Sciences. Shareholder/stock ownership; Gilead Sciences. A.J. Spindler: None. M. Stanislavchuk: Grants/research support; Amgen, AstraZeneca, Celgene, Eli Lilly, Galapagos, Gilead, Human Genome, Janssen, MSD, Nichi-Iko, Pfizer, and Roche. M. Greenwald: Grants/research support; AbbVie, Aclaris, Galapagos, Janssen, Lilly, and Nimbus.

Predicting Flare in Patients With Rheumatoid Arthritis in Biologic Induced Remission, on Tapering, and on Stable Therapy.

The tapering of biologic disease-modifying antirheumatic drug (b-DMARD) therapy for patients with rheumatoid arthritis (RA) in stable remission is frequently undertaken, but specific guidance on how to successfully taper is lacking. The objective of this study is to identify predictors of flare in patients in stable b-DMARD-induced clinical remission, who did or did not follow structured b-DMARD tapering. Patients with RA receiving b-DMARD treatment who had achieved sustained remission according to a Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) <2.6 for ≥6 months were offered tapering. Clinical, ultrasound (US) (total power Doppler [PD]/grayscale abnormalities), CD4+ T cell subsets, and patient-reported outcomes (PROs) were collected at inclusion. The primary endpoint was the occurrence of flare (loss of DAS28-CRP remission) over 12 months. Logistic regression analyses identified predictors of flare. Dichotomization into high/low-risk groups was based on 80% specificity using the area under the receiving operator curve (AUROC). Of 63 patients choosing tapering, 23 (37%) flared compared with 12 of 60 (20%) on stable treatment (P = 0.043). All patients who flared regained remission upon reinstating treatment. In the tapering group, flare was associated with lower regulatory T cell (Treg) (P < 0.0001) and higher CRP levels (P < 0.0001), erythrocyte sedimentation rate (P < 0.035), and inflammation-related cells (IRCs) (P = 0.054); stepwise modeling selected Tregs (odds ratio [OR] = 0.350, P = 0.004), IRCs (OR=1.871, P = 0.007), and CRP level (OR=1.577, P = 0.004) with 81.7% accuracy and AUROC=0.890. In the continued therapy group, modeling retained the tender joint count, total PD, and visual analog scale pain score, with 82.1% accuracy and AUROC=0.899. Most patients in the study were considered low risk of flare (80 of 123 patients [65%]). Only 5 of 37 (13.5%) of the low-risk patients who tapered flared, which was notable compared with the continued therapy group (20% flare). Flare on tapering b-DMARDs was predicted by lower Tregs and elevated inflammation biomarkers (IRCs/CRP level); flare on continued b-DMARDs was associated with raised pain parameters and US inflammation. Knowledge of these biomarkers should improve outcomes by targeted selection for tapering, and by increased monitoring of those on continued therapy predicted to flare.

Efficacy and safety of different Janus kinase inhibitors combined with methotrexate for the treatment of rheumatoid arthritis: a single-center randomized trial

ObjectiveTo compare the efficacy and safety between baricitinib (BARI) and tofacitinib (TOFA) for the treatment of the rheumatoid arthritis (RA) patients receiving methotrexate (MTX) in clinical practice.MethodsThis retrospective study recruited 179 RA patients treated with BARI (2–4 mg/d) or TOFA (10 mg/d) at The First Affiliated Hospital of Guangxi Medical University from September 2019 to January 2022. The rate of low disease activity (LDA) was used as the primary end point. Secondary end points included the Disease Activity Scale-28 (DAS-28)-C-reactive protein (CRP); the rate of DAS28-CRP remission; visual analogue scale (VAS) for pain, swollen joint, and tender joint counts; and adverse events at the 6-month follow-up. Several factors affecting LDA achievement were also analyzed.ResultsSeventy-four patients were treated with BARI and 105 were treated with TOFA, including 83.24% females, with a median (IQR) age of 56.0 (53.0–56.0) years old and disease duration of 12.0 (6.0–12.0) months. There was no difference of the rate of LDA between the BARI and TOFA treatment groups. All disease indices in the two groups were significantly improved, including a significantly lower VAS in the BARI group (P < 0.05), reflecting the drug efficacy after 1 and 6 months of treatment. The incidence of adverse reactions was similar in these two groups.ConclusionThe treatment efficacy and safety of BARI and TOFA in the RA patients were similar, but BARI was more effective in pain relief than TOFA. An older baseline age was more likely to achieve LDA in the BARI group, while a low baseline erythrocyte sedimentation rate (ESR) was more likely to achieve LDA in the TOFA group.

Should We Use bDMARDs as an Induction Therapy in Early and Severe Rheumatoid Arthritis? Results at 5years from the ERA UCLouvain Brussels Cohort.

This study sought to analyze the benefit of an early induction therapy with a biological disease-modifying anti-rheumatic drugs (bDMARD) during the first year of treatment with a 5-year follow-up in early rheumatoid arthritis (ERA). We included ERA patients from the UCLouvain Brussels cohort who met the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) 2010 classification criteria and were naïve to DMARDs. ERA patients were divided into two groups according to whether they received an induction bDMARD therapy or a standard therapy with methotrexate (MTX). Clinical response after the induction treatment at 6 and 12months followed by a MTX maintenance therapy at 36 and 60months was evaluated. Data from 470 ERA patients were collected, 189 received a bDMARD and 281 initiated MTX alone. In the bDMARD group, disease activity and HAQ were higher at baseline. A total of 391 patients were followed up to 5years. We then divided each group into two subgroups according to the last treatment they received at 5years: bDMARD > MTX (n = 95), bDMARD > bDMARD (n = 59); MTX > MTX (n = 134), MTX > bDMARD (n = 103). During the induction, we observed a clinical response with a large number of patients achieving DAS28-CRP remission. According to a treat-to-target (T2T) approach, remission rate was stable on MTX monotherapy or rescued by the addition or prolongation of a bDMARD. Interestingly, bDMARD followed by a MTX maintenance therapy experienced a stable and sustained DAS28-CRP remission rate in 53% of the ERA patients at year 5. Long-term remission is an achievable goal in ERA. Our results suggest that a bDMARD induction therapy followed by MTX maintenance therapy could be an interesting option.

Efficacy and safety of levilimab in combination with methotrexate in patients with active rheumatoid arthritis: 56-week results of phase III randomized double-blind placebo-controlled trial SOLAR

Background. Previously, 24-week results of phase III double-blind, placebo-controlled randomized clinical study (SOLAR) of levilimab in subjects with active rheumatoid arthritis (RA) proved a superiority of levilimab over placebo. Here we present 1-year efficacy and safety data of the SOLAR study.Objective – to evaluate the efficacy and safety of levilimab in combination with methotrexate (MTX) in subjects with MTX resistant active RA.Methods. The study was conducted at 21 clinical sites in Russia and Belarus. All randomized subjects have completed the study between November 2019 and October 2021.154 adults, aged ≥18 years with confirmed diagnosis of RA were randomly assigned (2:1) to receive either levilimab (162 mg, SC, QW) + MTX (n=102) or placebo + MTX (n=52).After W24 of the study all subjects continued to receive open label levilimab. Subjects who have achieved DAS28-CRP≤2.6 at W24 were switched to maintenance (Q2W) regimen of levilimab at W28 (LVL QW/Q2W and PBO/LVL Q2W arms). Those with DAS28-CRP&gt;2.6 at W28 continued with QW regimen (LVL QW and PBO/LVL QW arm). The PBO/LVL Q2W arm contained only one subject, thus not included in the analysis. The efficacy analysis was done in a population of all randomized subjects. Those with missing data due to study discontinuation or rescue therapy prescription were considered non-responders. Otherwise, the analysis was performed on complete cases.Safety was assessed through monitoring of adverse events (AEs) in a population of those, who received at least on dose of LVL (n=152).Results. Better response to treatment was observed in LVL QW/Q2W as it composed of those who reach DAS28-CRP≤2.6 at W24. At this time point 15/27 (55.6%) of them achieved ACR70; 23/27 (85.2%) achieved DAS28-CRP remission (&lt;2.6) and 7/27 (25.9%) achieved ACR/EULAR 2011 remission of RA. After switching to LVL Q2W, rates of ACR70 and DAS28-CRP&lt;2.6 did not significantly changed until W52: 17/27 (63.0%) and 21/27 (77.8%), respectively, yet the proportion of subject with ACR/EULAR 2011 remission further increased and reached 12/27 (44.4%).LVL QW arm was diminished by subjects who achieved high response to treatment at W24 and composed LVL QW/Q2W arm. Thus, ACR70, and remissions rate in this arm was close to zero at W24. However, continuation of LVL QW in those who not achieved DAS28-CRP≤2.6 at W24 induced ACR70 response in 37/75 (36.0%), DAS28-CRP remission in 35/75 (46.7%) and ACR/EULAR 2011 remission in 8/75 (10.7%) at W52.The most common adverse events (reported in ≥5% of subjects) were blood cholesterol increase (30.3%), ALT increase (23.0%), lymphocyte count decrease (17.1%), ANC decrease (16.4%). blood triglycerides increase (13.8%), bilirubin increase (11.2%), AST increase (9.9%), WBC decrease (9.9%), IGRA with Mycobacterium tuberculosis antigen positive (7.2%) and injection site reactions (5.9%). No deaths were occurred.Conclusions. Open label period confirmed the lasting efficacy and safety of levilimab in combination with MTX in subjects with MTX resistant active RA and suggested the possibility of switching to maintenance (Q2W) regimen in those who achieved remission of RA at week 24.

Comparison of Efficacy and Safety of Original and Biosimilar Adalimumab in Active Rheumatoid Arthritis in a Real-World National Cohort.

Background and Objectives: Real-world evidence should reflect the evidence obtained from controlled trials; therefore, the study aimed to compare biosimilar adalimumab (bADA) to original adalimumab (oADA) in terms of efficacy and safety in a real-life national cohort of rheumatoid arthritis (RA) patients. Materials and Methods: The following study is a prospective observational study in which we analyzed patients treated with reimbursed biologics from the Romanian Registry of Rheumatic Diseases (RRBR). RA cases must fulfill the 2010 classification criteria, as well as specific inclusion and exclusion criteria. The RRBR database was queried for all RA patients starting oADA or bADA (FKB327, GP2017, MSB11022, SB5 available) from 2 May 2019 (the first bADA initiation) until 26 March 2022 (study search date). Results: The study included 441 patients who started oADA (48.3%) or bADA (51.7%) in the same time period. At baseline, patients starting bADA had a significantly higher mean age and lower prevalence of women. After the first six months of treatment, there were no significant differences between the oADA and bADA regarding rates of Boolean (15.0% vs. 12.3%, p = 0.401), DAS28-CRP (32.4% vs. 34.2%, p = 0.686) and SDAI (16.4% vs. 14.0%, p = 0.483) remission rates. There were 107 cases of adverse events (AE): 81.3% on oADA and 18.7% on bADA. Notably, 51.4% of AE were infections. Regarding severity, 49.5% of AEs were mild, 34.6% were moderate, and 15.9% were severe. Conclusion: Biosimilar adalimumab showed similar efficacy and safety to original adalimumab after the first six months of treatment in RA patients from a national registry.

Psychosocial Burden Predicts Sustained Remission in Early Rheumatoid Arthritis: Unraveling the Complex Interplay of Well-Being and Disease Activity.

This study investigated how psychosocial aspects of disease affect the probability of achieving sustained remission in early rheumatoid arthritis (RA) and explored the directionality of this relationship. Data were analyzed from the randomized controlled Care in Early RA trial. Sustained remission was defined as a continued Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) of <2.6 from weeks 16 to 104. Patients completed the Short Form 36 (SF-36) health survey, Revised Illness Perception Questionnaire (IPQ-R), and the Utrecht Coping List. These psychosocial variables were studied at baseline and at week 16 as predictors of sustained remission with logistic regression. Next, subgroups of patients in remission at week 16 were identified by Latent Profile Analysis based on these psychosocial indicators. Time to first loss of remission was then compared between groups by Cox proportional hazards regression. Finally, directionality of associations between psychosocial indicators and DAS28-CRP was explored with cross-lagged panel models (CLPMs). Sustained DAS28-CRP remission was associated with higher SF-36 scores and less passive coping at baseline and with higher SF-36 scores and more positive IPQ-R outcomes at week 16. Among patients in DAS28-CRP remission at week 16 (n=287), 2 subgroups were identified: a low psychosocial burden group (n=231 of 287) and a high psychosocial burden group (n=56 of 287). The low psychosocial burden group retained remission longer (hazard ratio 0.51 [0.35-0.73]). In the CLPM, temporal relationships between psychosocial well-being and DAS28-CRP were complex, bidirectional, and disease-phase dependent. Suboptimal psychosocial well-being and negative illness perceptions predicted lower probability of sustained remission in an early RA cohort. Illness perceptions appeared to become more clinically relevant with time. Finally, 1 in 5 patients showed worse psychosocial outcomes despite early remission, and these patients tended to lose remission earlier.

Serum 14-3-3η as predictor of clinical remission and progression of structural damage in early rheumatoid arthritis following a treat-to-target strategy in a randomized controlled trial

Objective 14-3-3η is a proinflammatory mediator critical to joint destruction in rheumatoid arthritis (RA). We aimed to evaluate serum 14-3-3η for predicting disease activity and radiographic progression in patients with early RA in the double-blinded, randomized OPERA trial. Method 180 patients with early RA were randomized to receive methotrexate (MTX) + adalimumab or MTX + placebo in combination with glucocorticoid injections into swollen joints. Disease activity was measured using the 28-joint Disease Activity Score–C-reactive protein (DAS28-CRP). Clinical remission was defined as DAS28-CRP < 2.6. X-rays of hands and feet were evaluated by the Total Sharp van der Heijde score (TSS). Radiographic progression was defined as exceeding the smallest detectable change (1.8 TSS-units). Serum 14-3-3η was determined by enzyme-linked immunosorbent assay. Multivariate logistic regression models were used to identify predictors of DAS28-CRP remission at 6 months and radiographic progression at 12 months. Results Baseline 14-3-3η was a borderline significant independent predictor of radiographic progression at 12 months (odds radio = 1.02, 95% confidence interval 1.00–1.03, p = 0.05). In anti-cyclic citrullinated peptide antibody (ACPA)-negative patients, a moderate/high baseline 14-3-3η concentration increased the risk of radiographic progression at 12 months [4/51 (8%) vs 3/9 (33%), χ2 = 4.823, p = 0.028]. No value of 14-3-3η for predicting achievement of clinical remission was found. Conclusion Serum 14-3-3η was a borderline significant predictor of radiographic progression, particularly in ACPA-negative patients, but not of predicting achievement of clinical remission. Optimal cut-off levels of 14-3-3η for predicting radiographic progression in RA need further clarification.

OA26 Erythrocyte mean corpuscular volume as a surrogate marker for methotrexate polyglutamation during early treatment in rheumatoid arthritis

Abstract Background/Aims The long-term outcomes for patients with rheumatoid arthritis (RA) depend on early and effective disease control. Methotrexate remains the key first-line disease-modifying therapy for the majority of patients. The gradual onset of action of methotrexate has been proposed to be linked to the build-up of intracellular stores of the drug, achieved through the process of polyglutamation. This is a complex and expensive assay. Recent work has shown an association between the increase in mean corpuscular volume (MCV) of erythrocytes and improvements in disease activity. This study seeks to relate intracellular methotrexate and 5-methyl-tetrahydrofolate polyglutamate concentrations with changes in MCV and their association with early ‘steroid free’ remission in RA patients. Methods 68 drug-naïve, newly diagnosed RA patients were recruited form the Newcastle Early Arthritis Clinic (NEAC). These patients were followed up for 6 months with serial blood sampling and quantification of the erythrocyte methotrexate and 5-methyl-tetrahydrofolate polyglutamate levels by liquid chromatography-mass spectrometry (LC-MS). This was then related to the contemporaneous erythrocyte MCV values from the clinical monitoring bloods on those occasions and the treatment outcome at 6 months. The outcome measure used was 4 component DAS28CRP remission (&amp;lt;2.4) with only the baseline intramuscular steroid permitted for the definition of remission. Results The majority of patients displayed a gradual increase in MCV over the first 6 months of treatment (MCV change from patient baseline used to normalise the data). When grouped by the ‘steroid free’ remission outcome, there was a divergence in MCV change with greater MCV increases observed in those achieving remission from 4 months of treatment onward (p &amp;lt; 0.05). In the same patient group, the accumulation of longer chain methotrexate polyglutamates (chain length 3 to 5) was observed to follow a similar trend to MCV with higher polyglutamate concentrations in those achieving the remission outcome from 2 months of treatment (P &amp;lt; 0.05). When the contemporaneous MCV and MTX polyglutamate samples were compared, an association was observed between the longer chain MTX polyglutamates and the change in MCV values (R2 = 0.39, p &amp;lt; 0.001), but not between intracellular 5-methyl-tetrahydrofolate and MCV (R2 = 0.01, p = NS). Conclusion Change in MCV shows an association with early remission induction with MTX therapy in treatment-naïve RA patients. This change in MCV appears to be associated with the accumulation of intracellular MTX metabolites, rather than via depletion of intracellular folates. MCV may therefore represent a tractable proxy measure of methotrexate polyglutamation for application in larger studies or for the purpose of drug monitoring. Disclosure P.M. Brown: None. A.G. Pratt: None. A.E. Anderson: None. A.W. Morgan: None. J.D. Isaacs: None.

Use of tacrolimus for managing csDMARD-failed rheumatoid arthritis: A real- time experience from a single tertiary care centre

Aim: To evaluate the efficacy of tacrolimus in achieving disease activity score-28-c-reactive protein 3 [DAS28-CRP (3)] remission in patients managed with tacrolimus at the end of 24 week in a tertiary setting. Methodology: The retrospective study included RA patients who fulfilled American College of Rheumatology (ACR) 2010 criteria and managed by tacrolimus as an add-on to the background DMARD or as a substitute to conventional synthetic DMARD. Apart from demographic data, TJC, SJC, ESR and CRP were recorded at each visit. Subjects were grouped as those who achieved remission (DAS28-CRP (3) &lt;2.6) and not under remission (DAS28-CRP (3)&gt;2.6). Descriptive analysis was carried out for different variables in the classified groups, chi-square test for categorical variables and ANOVA and t-test to compare the continuous variables. Results: The study selected 100 patients who fulfilled the criteria for analysis. The corresponding number of subjects who received 4 mg, 3 mg, 2 mg, 1.5 mg and 1 mg of tacrolimus were 3, 23, 57, 2 and 15 respectively. The corresponding number of patients evaluated at 3, 6, 9 and 12 months were 100, 86, 71 and 56. Around 20% of the patients reached a state of remission by the end of 12 months. The DAS28-CRP (3) remission (&lt;2.6) was achieved in 7 (7%) out of 100 at the end of 3 months, which increased to 17 (20%) out of 86 by 6th month. Around 9 out of 57 maintained the remission till the end of 12 months and 11 (20%) out of 57, who were followed till 12th month, had moderate response. Discriminate function analysis showed that the age and duration of disease were strong predictors of achieving remission. Baseline DAS score and duration of illness at the time of introduction of tacrolimus negatively predicted the patients achieving remission.

Comparison of remission criteria in patients with rheumatoid arthritis treated with biologic or targeted synthetic disease-modifying anti-rheumatic drugs: results from a nationwide registry.

Background:Biologic or targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARD) are widely used for treatment of rheumatoid arthritis (RA), enabling patients to better achieve remission.Objective:The objective of the study was to investigate and compare remission rates in RA patients treated with different b/tsDMARDs during the period 2013–2019.Design:A longitudinal observational analysis was performed on data from a nationwide RA registry.Methods:Remission rates in the KOBIO-RA registry were defined by a disease activity score in 28 joints (DAS28), clinical disease activity index (CDAI), simplified disease activity index (SDAI), and Boolean-based assessment. After initiating treatment with b/tsDMARDs, yearly remission rates in response to b/tsDMARDs, either all or as subgroups (tumor necrosis factor-α inhibitors, tocilizumab, abatacept, and Janus kinase inhibitors), were investigated for 5 years. Sustained remission was defined as remission maintained for two consecutive years.Results:Patients (N = 1805) who completed at least one follow-up visit were analyzed (mean age = 55 years; 83.2% female). At month 12, 56.0% of patients achieved remission based on DAS28-C-reactive protein (CRP), 36.2% on DAS28-erythrocyte sedimentation rate (ESR), 10.4% on CDAI, 12.7% on SDAI, and 12.9% on Boolean criteria. Sustained remission rates were 62%, 40%, 13%, 11%, and 8% for the DAS28-CRP, DAS28-ESR, Boolean, SDAI, and CDAI remission criteria, respectively. Remission rates using the DAS28 definition varied most among the b/tsDMARD subgroups.Conclusion:Assessment of sustained remission using the CDAI, SDAI, or Boolean criteria is more stringent, yet congruous with the DAS28-based criteria in RA patients treated with b/tsDMARDs.

Tapering of Etanercept is feasible in patients with Rheumatoid Arthritis in sustained remission: a pragmatic randomized controlled trial

Objective In patients with rheumatoid arthritis (RA) in sustained remission, tapering of biological disease-modifying anti-rheumatic drugs can be considered. Tapering has already been investigated, but its feasibility remains to be determined. Therefore, we explored the feasibility of tapering etanercept in RA in a setting close to practice. Method Patients with RA in 28-joint Disease Activity Score (DAS28) remission (≥ 6 months) and treated with etanercept 50 mg weekly (≥ 1 year) were included in the pragmatic 1 year open-label multicentre randomized controlled TapERA (Tapering Etanercept in Rheumatoid Arthritis) trial. Patients were assigned to continue etanercept weekly or to taper to every other week (EOW). Patients who lost remission [DAS28–C-reactive protein (CRP) ≥ 2.6] were re-escalated to etanercept weekly. The primary outcome was the proportion of patients maintaining DAS28-CRP remission for 6 months. Results Sixty-six patients were randomized to etanercept weekly (n = 34) or EOW (n = 32). After 6 months, 26/34 patients (76%) in the weekly and 19/32 (59%) in the EOW group maintained disease control (p = 0.136). In the EOW group, 20/32 patients (63%) remained on their tapered treatment during the trial. Two patients reintroduced weekly etanercept themselves. Ten patients were re-escalated to etanercept weekly by the rheumatologist, after a median (interquartile range) interval of 3.0 (2.0–6.0) months. Among these patients, 7/10 regained remission after re-escalation, four of them at the next study visit. Conclusions Although non-inferiority could not be demonstrated, tapering of etanercept to EOW appeared feasible in patients in sustained remission.

POS0659 REAL WORD EXPERIENCE WITH TOFACITINIB IN PATIENTS WITH RHEUMATOID ARTHRITIS: AN INTERIM ANALYSIS FROM A FRENCH PROSPECTIVE OBSERVATIONAL STUDY DeFacTo

Background:Tofacitinib is an oral JAK inhibitor indicated for moderate to severe active rheumatoid arthritis (RA).Objectives:To present baseline patients characteristics and effectiveness data at 6 months of DeFacTo real life study (“IDentification of Factors predictive of Tofacitinib’s survival”).Methods:DeFacTo is an observational, open-label, prospective, multi-center, national study designed to evaluate the predictive factors of tofacitinib’s survival in patients with moderate-to-severe active rheumatoid arthritis according to the SmPC[1]. Here we present the 1st interim results involving a descriptive analysis of the 221 patients included between January 2019 and March 2020 (POP1). Effectiveness results at 6 months of 145 patients having ≥ 6 months follow-up (POP2) are also described.Results:The baseline characteristics of the POP1 patients (n = 221) were: 78.3% women with a mean age (± SD) of 60.4 ± 11.1 years, disease duration of 12.0 ± 9.8 years, TJC: 7.3 ± 5.7 and SJC: 5.1 ± 4.7; 44.0% of patients had erosions, 79.5% were RF+ and 75.9% were ACPA+. The mean CRP was 15.3 ± 21.8 mg/l, the ESR at one hour was 28.7 ± 23.6 mm, DAS28-4 CRP was 4.6 ± 1.0, DAS28-4 ESR was 4.9 ± 1.1 and the FACIT-Fatigue score was 27.6 ± 11.3. A total of 97.3% of patients had been previously treated by ≥1 csDMARD (mean number 1.9 ± 1.0) and 66.1% by b/tsDMARDs (mean number 2.9 ± 2.5), tofacitinib was prescribed as monotherapy (without csDMARD) in 49.3% of patients. The characteristics of the POP2 patients were similar to those of POP1. At 6 months in POP2, 29 patients have discontinued their treatment with tofacitinib. The results showed a decrease from baseline in inflammatory markers (CRP from 14.2±17.1 to 4.7±4.2 mg/l), pain (Pain VAS from 58.3±23.4 to 27.6±22.1) and DAS28 activity scores with 23% of patients in DAS28-CRP remission and 36% of patients in DAS28-CRP LDA (figure 1). This interim analysis didn’t identifyany new safety findings (Table 1).Conclusion:Preliminary results from this prospective observational study on the use of tofacitinib in patients suffering with RA in France indicate that its effectiveness and safety are similar to those found in the clinical studies[1-3]. In this study, tofacitinib was prescribed as monotherapy (without csDMARD) in more than 49% of cases.

A Low Gluten Diet Suppresses Disease Activity of Rheumatoid Arthritis

Background: This study aimed to evaluate the efficacy of a low gluten diet in the disease activity of Rheumatoid Arthritis (RA). Methods: Among 109 patients with RA enrolled in this study, 98 patients who completed 16 weeks on a low gluten diet regimen were included in the study. At baseline, we gave the patients the information about gluten-free and gluten-contained foods, and asked them to refrain from the daily gluten consumption during the experimental period. Results: The low gluten diet significantly improved DAS28-CRP and CDAI scores after 16 weeks. The percentages of patients achieving DAS28-CRP and CDAI-defined remission or LDA were significantly increased after 16 weeks. There was a significant increase in the percentage of the responders in EULAR treatment response after 16 weeks. Rheumatoid Factor (RF) but not C-reactive protein was significantly decreased after 16 weeks. When the self-reported level about adherence to the low gluten diet was divided into three categories, a significant decrease in DAS28-CRP, CDAI and RF was detected in the patients with the strict adherence to the low gluten diet. Conclusion: This study demonstrates that the strict adherence to a low gluten diet results in the decreased disease activity of RA.

A multi-biomarker disease activity score can predict sustained remission in rheumatoid arthritis

BackgroundReliable assessment of remission is important for the optimal management of rheumatoid arthritis (RA) patients. In this study, we used the multi-biomarker disease activity (MBDA) test to explore the role of biomarkers in predicting point remission and sustained remission.MethodsRA patients on > 6 months stable therapy in stable low disease activity (DAS28-ESR ≤ 3.2) were assessed every 3 months for 1 year. Baseline, intermittent (IR) and sustained (SR) remission were defined by DAS28-ESR, DAS28-CRP, simple disease activity index (SDAI), clinical disease activity index (CDAI) and ACR/EULAR Boolean criteria. Patients not fulfilling any remission criteria at baseline were classified as ‘low disease activity state’ (LDAS). Patients not fulfilling any remission criteria over 1 year were classified as ‘persistent disease activity’ (PDA). MBDA score was measured at baseline/3/6 months. The baseline MBDA score, the 6-month time-integrated MBDA score and MBDA biomarkers were used for analyses. The area under the receiver operating characteristic curve (AUROC) assessed the ability of the MBDA score to discriminate between remission and non-remission. Biomarkers were analysed at baseline using the Mann-Whitney test and over time using the Jonckheere-Terpstra trend test.ResultsOf 148 patients, 27% were in the LDAS, 65% DAS28-ESR remission, 51% DAS28-CRP remission, 40% SDAI remission, 43% CDAI remission and 25% ACR/EULAR Boolean remission at baseline. Over 1 year, 9% of patients were classified as PDA. IR and SR were achieved in 42%/47% by DAS28-ESR, 46%/29% by DAS28-CRP, 45%/20% by SDAI, 44%/21% by CDAI and 35%/9% by ACR/EULAR Boolean criteria, respectively. By all remission criteria, baseline MBDA score discriminated baseline remission (AUROCs 0.68–0.75) and IR/SR (AUROCs 0.65–0.74). The 6-month time-integrated MBDA score discriminated IR/SR (AUROCs 0.65–0.79). Baseline MBDA score and concentrations of IL-6, leptin, SAA and CRP were significantly lower in all baseline remission criteria groups vs LDAS. They and the 6-month time-integrated values were lower among patients who achieved IR/SR vs PDA over 1 year.ConclusionsThis study demonstrated that the MBDA score and its biomarkers IL-6, leptin, SAA and CRP differentiated between small differences in disease activity (i.e. between low disease activity and remission states). They were also predictors of remission over 1 year.

THU0093 EARLY REMISSION IS ASSOCIATED WITH LOWER FATIGUE LEVELS ON THE LONG TERM IN PATIENTS WITH RECENT ONSET RHEUMATOID ARTHRITIS

Background:Fatigue is mentioned as a symptom with high impact in many patients with Rheumatoid Arthritis (RA) and this symptom remains difficult to be managed by both the patient and the physician.Objectives:To investigate if rapid suppression of disease activity in early RA could impact fatigue complaints in the long run.Methods:For this study, we included patients from the 2-year pragmatic investigator-initiated Care in Early Rheumatoid Arthritis (CareRA) trial. Most patients were treated intensively, with different combinations of csDMARDs and glucocorticoid remission induction schemes, except one group without classic markers of poor prognosis that was treated with MTX weekly in monotherapy. Patients were followed up at least every 3 months, with more mandatory visits in the first 6 months of treatment. Clinical parameters including DAS28 components were registered at every visit. Fatigue was measured by the multi-dimensional fatigue inventory (MFI), a self-reported instrument consisting of 20 questions with a Likert scale from 1-5 as answer. These 20 questions can be subdivided in five subscales (0-20) of four questions (higher scores indicating higher fatigue levels): general fatigue, mental fatigue, physical fatigue, reduced activity and reduced motivation. General fatigue means the general feeling of being tired. Mental fatigue implicates concentration and memory problems. Physical fatigue implicates a lack of energy and strength. Reduced activity means that patients can do less activities for example on one day. Reduced motivation means that patients don’t want to plan or do things due to no motivation. MFI was obtained at baseline, at week 16, week 52 and week 104. Only patients with a filled-out MFI at baseline and available DAS28CRP at week 16 were included in this study.Patients were divided in 2 groups based on their response, defined as achieving or not achieving DAS28CRP remission (&lt;2.6) at week 16. These patients were classified as early responders and controls respectively. The 2 groups were compared by Mann-Whitney-U test. A generalized estimating equation (GEE) compared the 2 groups over the course of the 2-year trial per each of the 5 domains of the MFI, adjusting for baseline DAS28CRP and baseline MFI domain score.Results:Of the 379 patients recruited in the CareRA trial, 343 (90.5%) had a MFI score available at baseline and a DAS28CRP available at week 16 with 236 (68.8%) patients achieving remission, and 107 (31.2%) patients not achieving remission at week 16. After 2 years of treatment, the proportion of patients in DAS28CRP remission was still higher in the early responders versus controls (82.3% versus 63.5%, p=0.001). Every MFI domain after 2 years of treatment showed lower scores for early responders including general fatigue (p=0.017), physical fatigue (p=0.011), reduced activity (p=0.040) and mental fatigue (p=0.042) except reduced motivation (p=0.062) (see figure 1). GEE analysis demonstrated that all MFI domains differed over 2 years between patients in remission or not at week 16, including general fatigue (p&lt;0.001), physical fatigue (p&lt;0.001), reduced activity (p&lt;0.001), mental fatigue (p=0.037) and also reduced motivation (p=0.005).Figure 1.MFI domain scores at baseline and at week 104 per groupConclusion:Patients reaching remission after 16 weeks of treatment achieve lower fatigue levels over 2 years compared to patients not reaching this early remission. This study underlines the importance of early disease control. Successful early intensive treatment improves in the long run not only clinical outcomes but also an important patient preferred outcome such as fatigue.Disclosure of Interests:Diederik De Cock: None declared, Amber Nooyens: None declared, Delphine Bertrand: None declared, Veerle Stouten: None declared, Sofia Pazmino: None declared, Johan Joly: None declared, Rene Westhovens Grant/research support from: Celltrion Inc, Galapagos, Gilead, Consultant of: Celltrion Inc, Galapagos, Gilead, Speakers bureau: Celltrion Inc, Galapagos, Gilead, Patrick Verschueren Grant/research support from: Pfizer unrestricted chair of early RA research, Speakers bureau: various companies