Abatacept Research Articles

Differential long-term retention of biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis by age group from the FIRST registry

BackgroundThe effectiveness and safety of biological disease-modifying antirheumatic drugs (bDMARDs) by age group (< 65, 65–74, and ≥ 75 years) are uncertain. We examined retention rates reflecting the effectiveness and safety of bDMARDs in actual clinical practice for clarifying optimal therapeutic strategies for rheumatoid arthritis (RA) by age groups.MethodsData of patients who were treated with tumor necrosis factor inhibitors (TNFi), abatacept (ABA), and tocilizumab (TCZ) between February 2011 and April 2017 were collected from a prospective observational registry of RA patients. A total of 1362 patients were enrolled, of which 695 were aged < 65 years, 402 were aged 65–74 years, and 265 were aged ≥ 75 years. Primary outcome was the drug retention rate in adjusted data using inverse probability of treatment weighting based on generalized propensity scores.ResultsIn patients aged < 65 years, 3-year retention rates of TNFi, ABA, and TCZ were 43%, 47%, and 69%, respectively (ABA versus TCZ, p = 0.017; TNFi versus TCZ, p = 0.002). In patients aged 65–74 years, 3-year retention rates of TNFi, ABA, and TCZ were 44%, 53%, and 60%, respectively (TCZ versus TNFi, p = 0.034). In patients aged ≥ 75 years, 3-year retention rates for TNFi, ABA, and TCZ were 38%, 63%, and 58%, respectively (ABA versus TNFi, p = 0.017).ConclusionsWe found that the effectiveness and safety of TCZ were maximal in patients aged < 75 years and that patients aged ≥ 75 years might be suitable candidates for TCZ and ABA therapy. The use of therapeutic strategies appropriate to each age group might improve the outcomes of bDMARD therapy for RA.

Survival of bDMARDs in bionaive patients with rheumatoid arthritis: data from a retrospective 12-month follow-up

Analysis of survival on biological therapy in previously bionaive patients with rheumatoid arthritis (RA) during the first year of therapy in real clinical practice. The retrospective study included 204 adult patients with RA. In the hospital, patients were first prescribed therapy with various biological disease-modifying antirheumatic drugs (bDMARDs): infliximab, adalimumab, etanercept, certolizumab pegol, tocilizumab, abatacept (ABA), rituximab (RTM). Patients were divided by age in accordance with the classification adopted by WHO. Clinical forms of RA were presented: RA, seropositive for rheumatoid factor, RA, seronegative for rheumatoid factor, RA with extra-articular manifestations, adult-oneset Stills disease, juvenile RA. The reasons for the cancellation of bDMARD during the first year of treatment were: insufficient effectiveness (including primary inefficiency), adverse events, administrative reasons, clinical and laboratory remission, death. A year after being included in the study, treatment was continued in 92 (45%) patients and was discontinued in 112 patients. The average time of treatment amounted to 0.750.33 years. The longest duration of treatment was in the RTM and ABA groups (0.920.22 and 0.830.29 years, respectively). In 56 (50%) patients, bDMARD was canceled due to insufficient effectiveness (including primary inefficiency), 28 patients (25%) due to the development of adverse reactions, 19 (17%) patients for administrative reasons, 7 (6.25%) patients due to drug remission. During the first year of therapy, there were 2 (1.75%) deaths due to severe comorbid conditions in patients, one of whom received RTM, the other tocilizumab. Study showed that 45% of patients with RA continue treatment with first-time bDMARD for more than 12 months. The most common reason for discontinuation of therapy was its lack of effectiveness. The best survival rate of bDMARDs was observed in RTM and ABA. When selecting bDMARD in each case, it is necessary to take into account the continuity at all stages of treatment.

SAT0151 EFFICACY AND SAFETY OF UPADACITINIB VERSUS ABATACEPT IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS AND PRIOR INADEQUATE RESPONSE OR INTOLERANCE TO BIOLOGIC DISEASE-MODIFYING ANTI-RHEUMATIC DRUGS (SELECT-CHOICE): A DOUBLE-BLIND, RANDOMIZED CONTROLLED PHASE 3 TRIAL

Background:Upadacitinib (UPA) is an oral, reversible, selective JAK 1 inhibitor approved for the treatment of moderate to severe rheumatoid arthritis (RA). The efficacy/safety of UPA has been demonstrated in phase 3 studies, including superiority to adalimumab in patients (pts) with prior inadequate response (IR) to methotrexate.1-4Objectives:To assess the efficacy/safety of UPA vs abatacept (ABA) in pts with prior IR or intolerance to biologic DMARDs (bDMARDs).Methods:Pts were randomized to once daily UPA 15 mg or intravenous ABA (at Day 1, Weeks [Wks] 2, 4, 8, 12, 16 and 20 [&lt; 60 kg: 500 mg; 60-100 kg: 750 mg; &gt;100 kg: 1,000 mg]), with all pts continuing background stable csDMARDs. The study was double-blind for 24 wks. Starting at Wk 12, pts who did not achieve ≥20% improvement from baseline (BL) in both tender and swollen joint counts at two consecutive visits, had background medication(s) adjusted or initiated. The primary endpoint was change from BL in DAS28(CRP) at Wk 12 (non-inferiority). The non-inferiority of UPA vs ABA was tested using the 95% CI of treatment difference against a non-inferiority margin of 0.6. The two key secondary endpoints at Wk 12 were change from BL in DAS28(CRP) and the proportion of pts achieving clinical remission (CR) based on DAS28(CRP), defined as DAS28(CRP) &lt;2.6. Both endpoints were to demonstrate the superiority of UPA vs. ABA. Treatment-emergent adverse events (TEAEs) are reported up to Wk 24 for all pts who received at least one dose of study drug.Results:Of 612 pts treated; 67% of pts had received 1 prior bDMARD, 22% received 2 prior bDMARDs, and 10% received ≥ 3 prior bDMARDs. 549 (90%) completed 24 wks of treatment. Common reasons for study drug discontinuation were AEs (UPA, 3.6%; ABA, 2.6%) and withdrawal of consent (UPA, 1.7%; ABA, 2.6%).Non-inferiority and superiority were met for UPA vs ABA at Wk 12 for change from BL in DAS28(CRP) (-2.52 vs -2.00; -0.52 [-0.69, -0.35]; p &lt;0.001 for UPA vs ABA). UPA also demonstrated superiority to ABA in achieving DAS28(CRP) &lt;2.6 (30.0% vs 13.3%; p &lt;0.001 for UPA vs ABA; Figure 1). Improvements in disease activity and remission rates were maintained through Wk 24. The proportions of pts achieving low disease activity (defined as DAS28(CRP) ≤3.2), ACR20, ACR50, and ACR70 responses were greater with UPA compared with ABA at Wk 12 (nominal p &lt;0.05). More stringent outcome measures – CR, ACR50, and ACR70 responses - remained higher with UPA than ABA through Wk 24 (nominal p &lt;0.05). Incidence of serious TEAEs, AEs leading to discontinuation, hepatic disorders, and CPK elevations were numerically higher with UPA versus ABA (Figure 2). Eight cases of herpes zoster were reported (4 in each treatment arm). No malignancies were reported. One case of adjudicated MACE, two adjudicated cases of VTE (1 pt with DVT and 1 pt with PE; both pts had at least one risk factor for VTE), and one treatment-emergent death were reported with UPA.Conclusion:In RA pts with a prior IR or intolerance to bDMARDs, UPA demonstrated superior improvement in signs and symptoms vs ABA based on change in DAS28(CRP) and in achieving CR at Wk 12. The safety profile of UPA was consistent with the phase 3 RA studies with no new risks identified.

SAT0104 MAINTENANCE OF SDAI REMISSION AND PATIENT-REPORTED OUTCOMES (PROS) FOLLOWING DOSE DE-ESCALATION OF ABATACEPT IN MTX-NAÏVE, ANTI-CITRULLINATED PROTEIN ANTIBODY (ACPA)+ PATIENTS WITH EARLY RA: RESULTS FROM AVERT-2, A RANDOMISED PHASE IIIB STUDY

Background:The Phase IIIbAssessingVeryEarlyRATreatment (AVERT)-2 trial (NCT02504268) evaluated SC abatacept (ABA) + MTX vs ABA placebo (PBO) + MTX in ACPA+ patients (pts) with early, active RA.1Results from the 56-wk induction period (IP) showed a significantly greater proportion of pts treated with ABA + MTX (vs MTX alone) reported clinically meaningful improvements in HAQ-DI, global disease activity and pain, which were sustained at 52 wks.2Objectives:To report maintenance of SDAI remission and PROs from the AVERT-2 de-escalation (D-E) period.Methods:Pts received blinded SC ABA (125 mg once wkly [QW]) + MTX or ABA PBO + MTX induction treatment for 56 wks. In this analysis, pts who completed induction with ABA + MTX and had sustained SDAI remission (≤3.3 at Wks 40 and 52) were re-randomised 1:1:1 to ABA QW + MTX, stepwise D-E (ABA every other wk + MTX for 24 wks then ABA PBO + MTX for 24 wks), or ABA QW + MTX PBO for 48 wks in the D-E period. PROs included physical function (HAQ-DI [0–3; decrease=improvement] and Short-Form 36 [SF-36] v2.0 Physical Functioning Scale [PFS]; 0–100; increase=improvement), and fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F] score; 0–52; decrease=improvement). Endpoints included: proportion of pts in SDAI remission and pts with HAQ-DI response (decrease from IP Day [D]1 in HAQ-DI ≥0.30); adjusted mean change (adMC) from D-E D1 in HAQ-DI, SF-36 PFS or FACIT-F to D-E Wk 48. adMCs were estimated using a mixed effect model with repeated measures.Results:147 ABA + MTX-treated pts were re-randomised in the D-E period. Across re-randomised arms, the range of mean scores was 1.87–2.52 for SDAI and 0.18–0.30 for HAQ-DI at entry into D-E period (D-E D1). 74% of pts receiving ABA QW + MTX maintained SDAI remission at D-E Wk 48 (Fig 1); this proportion was higher than in the ABA withdrawal and ABA QW + MTX PBO arms. Pts continuing ABA QW + MTX maintained HAQ-DI response during D-E (Fig 1), but by D-E Wk 48 the proportion of pts with HAQ-DI response in the ABA withdrawal arm declined by 30%. At D-E Wk 48, a small numerical decrease (adMC –0.04) in HAQ-DI was observed in the ABA QW + MTX arm; increases were seen in the withdrawal (adMC 0.26) and ABA QW + MTX PBO arms (adMC 0.16). By D-E Wk 48, SF-36 PFS increased (adMC 1.68) in the ABA QW + MTX arm but decreased in the withdrawal (adMC –3.34) and ABA QW + MTX PBO (adMC –1.45) arms. FACIT-F score increased during D-E in all arms, but the increase at D-E Wk 48 was lower in the ABA QW + MTX arm (adMC 0.79) vs the withdrawal (adMC 4.12) and ABA QW + MTX PBO (adMC 2.41) arms. Similar trends were seen for other PROs including Work Productivity and Activity Impairment-RA; while activity impairment remained stable in the ABA QW + MTX arm, there was a trend for worsening in the withdrawal arm.Conclusion:In the AVERT-2 D-E period, continued combination therapy (abatacept + MTX) resulted in maintenance of benefits on PROs, particularly physical functioning, in seropositive pts with early RA. D-E of abatacept followed by complete withdrawal was associated with the greatest loss of remission as well as worsening of PROs. The PRO results corresponded well to the maintenance of clinical (SDAI) remission.

FRI0105 EVALUATION OF CXCL13 AND ICAM1 SERUM LEVELS AS PREDICTORS OF CLINICAL RESPONSE TO ABATACEPT IN RHEUMATOID ARTHRITIS.

Background:Soluble intercellular adhesion molecule 1 (ICAM1) and C-X-C motif chemokine 13 (CXCL13) were described as differentially associated with two major subtypes of synovitis in rheumatoid arthritis (RA). Raised serum levels of ICAM1 (which is upregulated in synovial fibroblasts in response to TNFα), and of CXCL13 (which is expressed by synovial follicular dendritic cells and activated mature antigen-experienced T-helper cells), are associated with a myeloid or lymphoid synovial phenotype, respectively (1). It has been suggested that a preferential clinical response to anti-TNFα, as compared to anti-IL-6R monotherapy, can be predicted by measuring these two biomarkers (2). No information is available on the possible utility of these biomarkers in RA patients treated with abatacept (ABA), a T-cell co-stimulation blocker.Objectives:To analyze the effect of ABA on ICAM1 and CXCL13 serum levels in RA and to verify whether they predict the response to the drug.Methods:63 RA patients [F/M=51/12; median (10th-90thpercentile) age=60 (41-72) years; CRP-DAS28=4.6 (3.3-5.8); ACPA positive: 86%], before and after 6 months of treatment with ABA + methotrexate and 22 sex and age-matched healthy controls (HC) were evaluated. Serum ICAM1 and CXCL13 levels were dosed by commercial ELISA (Life Technologies and R&amp;D). Response to treatment was defined with the EULAR criteria.Results:CXCL13 serum levels were higher in RA at baseline than in HC [136 (42-325) vs 32 (19-57) pg/ml, p&lt;0.01], while no difference was observed in ICAM1 [186 (125-276) vs 184 (153-246) ng/ml, p=0.9]; positive correlations between ICAM1 and CRP (r:0.28; p=0.03) and CXCL13 levels and CRP (r:0.40; p&lt;0.01) and CRP-DAS28 values (r:0.27, p=0.05) were found. After therapy with ABA, a reduction of CXCL13 was observed [136 (42-325) vs 94 (29-319) pg/ml, p&lt;0.01], both in responders [n: 37: 151 (57-462) vs 97 (26-329) pg/ml; p&lt;0.01] and non-responders (n: 14: 142 (68-293) vs 89 (42-198) pg/ml; p=0.01]. Not significant variation of ICAM1 serum levels was found in the entire cohort [186 (125-276) vs 190 (113-252) ng/ml, p=0.06]. However, a significant decrease was observed in non-responders [222 (169-302) vs 186 (110-233) ng/ml, p=0.02]. At baseline, no significant difference was found among patients seropositive for ACPA if compared with the negative ones [ACPA+ vs ACPA- for ICAM1 [187 (123-280) vs 177 (134-258) ng/ml; p=0.7] and for CXCL13 [143 (42-368) vs 113 (56-270) pg/ml; p=0.4]].Conclusion:Our results confirmed that CXCL13 serum levels are directly correlated with disease activity and demonstrated that ABA therapy induces their reduction. These findings suggest that the co-stimulation blockade at central level and/or in the synovium lead to a reduced production of CXCL13. We could not demonstrate that CXCL13 levels predict the clinical response to ABA in this cohort of patients.

FRI0107 EFFECTIVENESS OF ABATACEPT ON CLINICAL DISEASE ACTIVITY AND RADIOGRAPHIC PROGRESSION IN RHEUMATOID ARTHRITIS PATIENTS IN DAILY CLINICAL PRACTICE IN JAPAN: COMPARISONS ACCORDING TO ACPA STATUS

Background:The clinical effectiveness of abatacept (ABA) in rheumatoid arthritis (RA) patients has been reported to be higher when the patients’ anti-cyclic citrullinated peptide antibody (ACPA) status is positive. The report from the ORA registry demonstrated that the ACPA positivity was associated with a better response to ABA [1]. In a sub-analysis of the AMPLE trial, patients with very high ACPA titers who were treated with ABA had a statistically significant response compared to patients with lower titers [2]. However, these studies did not demonstrate the data regarding the structural progression.Objectives:This study aimed to evaluate the effectiveness of ABA on the clinical disease activity as well as the radiographic progression in patients with RA in the clinical settings.Methods:All eligible patients were registered in the TBCR, a Japanese multicenter registry system for RA patients treated with biologics [3]. The present study included 553 consecutive patients whose ACPA data were obtained, treated with ABA and observed for longer than 52 weeks. We primarily compared the status of disease activity (SDAI) and radiographic progression (van der Heijde modified total Sharp score: mTSS) between ACPA-positive [ACPA (+)] and ACPA-negative [ACPA (-)] RA patients. The ACPA positive was defined as ≥13.5 U/ml of anti-CCP antibody.Results:Number of cases was 446/ 107 [ACPA (+)/ ACPA (-)], respectively. Baseline characteristics between groups were quite similar; mean age was 68.0/ 67.3 years, rate of methotrexate (MTX) use rate was 41.2/ 50.0%, rate of bio-naive was 28.0/ 31.8%, and mean SDAI score was 22.2/ 20.8. Significant difference was observed in mean change in SDAI score from baseline to 52 weeks between the ACPA (+) and ACPA (-) group (-13.4 vs -9.9, p = 0.027) (Figure 1A). Proportion of patents that achieved low disease activity (LDA; SDAI ≤11) at 52 weeks was significantly higher in the ACPA (+) group compared to the ACPA (-) group (72.1 vs 56.0%, p &lt; 0.01) (Figure 1B). In univariate and multivariate logistic regression analysis, ACPA positivity was an independent predictor for achievement of LDA at 52 weeks (Table). There observed no significant difference between ACPA (+) and ACPA (-) group in the proportion of patients that achieved structural remission (ΔmTSS ≤0.5) at 52 weeks (66.2 vs 62.1%) (Figure 2A) as well as mean change in mTSS (1.66 vs 1.17), erosion score (0.60 vs 0.53), and joint narrowing (JSN) score (1.06 vs 0.64) (Figure 2B).Table.UnivariateMultivariateVariablesOR (95%CI)p-valueadjusted OR (95%CI)p-valueAge0.99 (0.98-1.01)0.4391.00 (0.97-1.02)0.749male (vs female)1.12 (0.70-1.80)0.6340.79 (0.40-1.58)0.511disease duration0.99 (0.97-1.00)0.0530.99 (0.97-1.01)0.468Biologics-naïve1.23 (0.81-1.85)0.3351.18 (0.67-2.08)0.575Concomitant MTX use1.12 (0.75-1.69)0.5851.14 (0.66-1.95)0.649Concomitant PSL use0.82 (0.55-1.23)0.3290.97 (0.58-1.64)0.923SDAI @baseline0.96 (0.94-0.97)&lt;0.0010.96 (0.94-0.98)&lt;0.001mHAQ @baseline0.50 (0.36-0.69)&lt;0.0010.57 (0.38-0.86)0.008ACPA positive2.03 (1.29-3.17)0.0022.61 (1.36-5.00)0.004Bold italic, p&lt;0.05Conclusion:Consistent with previous reports, the ACPA-positive group demonstrated significantly higher LDA achievement rate at 52 weeks and indeed the ACPA positivity was significantly associated with LDA achievement in multivariate analysis. However, the ACPA-negative group demonstrated quite similar transition of SDAI score and LDA achievement rate except at 52 weeks compared with the ACPA-positive group. Additionally, there was no significant difference in the structural progression at 52 weeks between the groups. ABA treatment may be considered not only in the ACPA-positive RA patients but also in the ACPA-negative patients in the clinical practice.

THU0171 EFFICACY OF ABATACEPT FOR SUPPRESSING RADIOGRAPHIC PROGRESSION OF CERVICAL LESIONS IN PATIENTS WITH RHEUMATOID ARTHRITIS COMPARISON WITH METHOTREXATE TREATMENT; TWO YEARS OF FOLLOW-UP ~A MULTICENTER REGISTRY STUDY ~

Background:Cervical lesions are known to occur at high frequency as a complication of rheumatoid arthritis (RA). Treatment with biological agents are more clinically effective than the DMARDs that were in use previously, in particular, with their efficacy in suppressing joint destruction having been emphasized. We reported the efficacy of infliximab, anti-tumor necrosis factor antibodies for suppressing the radiographic progression of RA cervical lesions at ACR2009, EULAR2010, 11, 12, 13, 14,16 and 18. However there is still few studies of efficacy of against RA cervical lesions of Abatacept (ABT) that inhibits T cell activation by binding to CD80/86.Objectives:To evaluate the efficacy of ABT for suppressing the radiographic progression of RA cervical lesions comparison with MTX for 2 years.Methods:We used ABT or MTX for treating Japanese patients with active RA who fulfilled the ACR criteria in 1987. The final study cohort of each 60 and 75 patients received continuous ABT and MTX treatment for at least 2 years. For evaluation of cervical lesions, the atlanto-dental interval (ADI), the space available for the spinal cord (SAC), and the Ranawat value were measured by plain lateral radiographs in the flexion position, at initiation and Year 1,2.Results:In the patients receiving ABT (n=60) and MTX (n =75), the number of female were each 48(80%) and 52(69%) cases(p=0.160). The mean age was 67.7 ± 12.9 and 63.6 ± 11.0 years old (p=0.004); disease duration was 16.7 ± 14.2 and 8.0 ± 9.5 years (p&lt;0.001) and the mean dose of MTX was 8.4 ± 3.6 and 8.2 ± 2.9 mg/w (p=0.804). Clinical findings related to RA were as follows; CRP 2.2± 2.1 and 1.7± 2.3 mg/dl(p=0.008); ESR 47.2 ± 23.4 and 31.9 ± 21.8mm/h(p&lt;0.001); MMP3 253 ± 280 and 223 ± 350ng/ml(p=0.003); the number of RF-positive 57(95%) and 60(80%) cases(p=0.011); DAS28-ESR 5.13 ± 0.99 and 4.30 ± 1.38 (p&lt;0.001); ADI 3.6 ± 2.1 and 2.6 ± 1.6mm(p=0.003); SAC 18.5 ± 2.8 and 20.8 ± 2.5mm(p&lt;0.001) and Ranawat value 14.4 ± 1.9 and 16.0 ± 1.5mm (p&lt;0.001). The respective changes in cervical lesion parameters after 1 year were as follows: ADI: 0.20 ± 0.40 and 0.27 ± 0.45 mm (p = 0.367); SAC: −0.12 ± 0.32 and −0.17 ± 0.38 mm (p = 0.359); and Ranawat value: −0.15 ± 0.36 and −0.13 ± 0.34 mm (p = 0.783). The respective changes in cervical lesion parameters after 2 years were as follows: ADI: 0.35 ± 0.58 and 0.55 ± 0.70 mm (p = 0.099); SAC: −0.25 ± 0.47 and −0.45 ± 0.62 mm (p = 0.047); and Ranawat value: −0.23 ± 0.47 and −0.33 ± 0.55 mm (p = 0.293) in the patients receiving ABT and MTX (Fig. 1). The numbers of patients who did not showed progression in ADI, SAC and Ranawat value were each 42(70%) and 43(57%) cases(p=0.130); 46(77%) and 46(61%) cases(p=0.057) and 47(78%) and 53(71%) cases(p=0.313) after 2 years. Also the number who was able to suppress progression in all three parameters were each 42 cases (70%) receiving ABT and 43 cases (57%) receiving MTX (p=0.130) after 2 years (Fig. 2).Conclusion:This study suggested that ABT treatment can be used to suppress the progression of RA cervical lesions more than MTX treatment.Disclosure of Interests:Yasuhide Kanayama: None declared, Toshihisa Kojima Grant/research support from: Chugai, Eli Lilly, Astellas, Abbvie, and Novartis, Consultant of: AbbVie, Speakers bureau: AbbVie, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eli Lilly, Janssen, Mitsubishi Tanabe, Pfizer, and Takeda, Yuji Hirano Speakers bureau: Tanabe-Mitsubishi, Pfizer, Eisai, Abbie, Chugai, Bristol-Meyers, Jansen, Astellas, UCB, Eli-Lilly, Asahikasei, Daiichi-Sankyo, Amgen, Nobunori Takahashi Speakers bureau: AbbVie, Asahi Kasei, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Janssen, Mitsubishi Tanabe, Ono, Pfizer, Takeda, and UCB Japan, Yukiyoshi Oishi: None declared, Naoki Ishiguro Grant/research support from: AbbVie, Asahi Kasei, Astellas, Chugai, Daiichi-Sankyo, Eisai, Kaken, Mitsubishi Tanabe, Otsuka, Pfizer, Takeda, and Zimmer Biomet, Consultant of: Ono, Speakers bureau: Astellas, Bristol-Myers Squibb, Daiichi-Sankyo, Eli Lilly, Pfizer, and Taisho Toyama

SAT0101 ABATACEPT IN RHEUMATOID ARTHRITIS ASSOCIATED-INTERSTITIAL LUNG DISEASE: SHORT TERM OUTCOME AND PROGNOSTIC FACTORS

Background:The prevalence of interstitial lung disease (ILD) in rheumatoid arthritis (RA) varies in the medical literature from 1% to 67% and is a major cause of mortality. Previous works have identified increased age, smoking and anticytrullinated protein antibodies (ACPA) titre as risk factors for RA-ILD (RA-ILD). Conventional treatments for RA may lead to a new onset or worsening of RA-ILD, so treatment should be identified to prevent the onset or exacerbation of RA-ILD. Studies have shown that abatacept (ABA) may improve the outcome of RA-ILD.Objectives:The aim of our study is to evaluate ABA effectiveness and safety in patients with RA-ILD.Methods:We enrolled RA-ILD patients who started treatment with ABA. All patients underwent thoracic high-resolution computed tomography (HRCT) at the beginning of ABA treatment and after 18 months of therapy. HRCT abnormalities were evaluated using a a computer-aided method (CaM). At each visit clinical, laboratory and respiratory function characteristics were collected and the Clinical Disease Activity Index (CDAI) and the Health Assessment Questionnaire Disability Index (HAQ-DI) for disease activity and functional disability were measured. The cohort was divided into three groups based on the CaM-HRCT results: patients with a lung fibrosis progression of 15% or more were defined as “worsened”, those with a reduction of 15% or more were defined as “improved”, all other patients were defined as “stable”. The 15% threshold of change, derived from the CaM assessment, results from the determination of the standard deviation of the mean value change after 18 months of follow-up of the cohort. The multivariate regression model was used to assess the strength of the association between RA characteristics and HRCT response to ABA.Results:Forty-four patients (81% women) with a mean age of 59.1±8.0 years and a mean duration of the disease of 7.5±3.1 years were recruited. Twenty-three (52.3%) patients were positive for ACPA and 28 (63.6%) for rheumatoid factor. Five patients (11.4%) showed deterioration of ILD, 31 (70.6%) were in the “stable” group, and 7 patients (16.0%) experienced improvement over a mean follow-up period of 18 months. The factors related to ILD deterioration were use of methotrexate (MTX) (p=0.0078), and current smoking habit (p=0.0054), according to multivariate regression analysis (Table).Conclusion:Treatment with ABA is associated with an RA-ILD stability or improvement rate of 86.6% of patients, while the worsening rate is 11.4%. Concomitant treatment with MTX and current smoking habit are factors associated with RA-ILD worsening. MTX discontinuation and smoking cessation should be strongly promoted in patients with RA-ILD.

OP0231 COMPARATIVE EFFECTIVENESS OF JAK-INHIBITORS, TNF-INHIBITORS, ABATACEPT AND IL-6 INHIBITORS IN AN INTERNATIONAL COLLABORATION OF REGISTERS OF RHEUMATOID ARTHRITIS PATIENTS (THE “JAK-POT” STUDY)

Background: In many countries, JAK-inhibitors (JAKi) have only recently been approved as treatment for patients with rheumatoid arthritis (RA). Objectives: To evaluate the effectiveness of JAKi compared to bDMARDs in RA patients in the real-world population in an international collaboration of registers (the “JAK-pot” collaboration). Methods: Patients initiating either JAKi, TNFi, IL-6i or abatacept (ABA) during a time period when JAKi were available in each country (19 registers, Table) were included. We compared the effectiveness of JAKi and bDMARDs in terms of retention using crude and adjusted survival analysis. Missing covariates were imputed using multiple imputation. Results: Among 25521 included patients, 6063 initiated a JAKi, 13879 a TNFi, 2348 ABA, and 3231 an IL-6i. Patients were on average 55 years old, with a mean disease duration 10 years, mostly seropositive (67%), female (77%) and with moderate disease activity at treatment initiation. The main reason of stopping treatment was ineffectiveness (49%), followed by adverse events (21%). Patients on JAKi were treated more often as monotherapy, had higher CRP and disease activity at baseline and had experienced more previous ts/bDMARDs. Crude median retention was 1.4 (95% CI 1.2-1.5) years for JAKi, 1.6 (1.6-1.7) for TNFi, 1.5 (1.3-1.7) for IL6i and 1.1 (1.0-1.3) for ABA. After adjustment, the hazard ratio (HR) for discontinuation tended to be lower for JAKi (HR 0.86 (0.65-1.13)) compared to TNFi, but comparable for ABA (1.02 (0.94-1.10)) and IL6i (0.99 (0.88-1.10)) (Figure 1). HRs differed notably between countries (Figure 2). Conclusion: The adjusted overall drug retention of JAKi tended to be higher than for TNFi, with large variation between countries. Other measures of effectiveness, such as the evaluation of CDAI remission and low disease activity are planned to shape a more comprehensive picture of JAKi effectiveness in the real world. Disclosure of Interests: Kim Lauper: None declared, Denis Mongin: None declared, Sytske Anne Bergstra: None declared, Denis Choquette Grant/research support from: Rhumadata is supported by grants from Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Consultant of: Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Speakers bureau: Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Catalin Codreanu Consultant of: Speaker and consulting fees from AbbVie, Accord Healthcare, Alfasigma, Egis, Eli Lilly, Ewopharma, Genesis, Mylan, Novartis, Pfizer, Roche, Sandoz, UCB, Speakers bureau: Speaker and consulting fees from AbbVie, Accord Healthcare, Alfasigma, Egis, Eli Lilly, Ewopharma, Genesis, Mylan, Novartis, Pfizer, Roche, Sandoz, UCB, Diederik De Cock: None declared, Lene Dreyer: None declared, Ori Elkayam Speakers bureau: AbbVie, BMS, Pfizer, Roche, Sanofi-Aventis, Novartis, Jansen, Kimme Hyrich Grant/research support from: Pfizer, UCB, BMS, Speakers bureau: Abbvie, Florenzo Iannone Consultant of: Speaker and consulting fees from AbbVie, Eli Lilly, Novartis, Pfizer, Roche, Sanofi, UCB, MSD, Speakers bureau: Speaker and consulting fees from AbbVie, Eli Lilly, Novartis, Pfizer, Roche, Sanofi, UCB, MSD, Nevsun Inanc: None declared, Eirik kristianslund: None declared, Tore K. Kvien Grant/research support from: Received grants from Abbvie, Hospira/Pfizer, MSD and Roche (not relevant for this abstract)., Consultant of: Have received personal fees from Abbvie, Biogen, BMS, Celltrion, Eli Lily, Hospira/Pfizer, MSD, Novartis, Orion Pharma, Roche, Sandoz, UCB, Sanofi and Mylan (not relevant for this abstract)., Paid instructor for: Have received personal fees from Abbvie, Biogen, BMS, Celltrion, Eli Lily, Hospira/Pfizer, MSD, Novartis, Orion Pharma, Roche, Sandoz, UCB, Sanofi and Mylan (not relevant for this abstract)., Speakers bureau: Have received personal fees from Abbvie, Biogen, BMS, Celltrion, Eli Lily, Hospira/Pfizer, MSD, Novartis, Orion Pharma, Roche, Sandoz, UCB, Sanofi and Mylan (not relevant for this abstract)., Burkhard Leeb Grant/research support from: chairman of BioReg, Consultant of: AbbVie, Pfizer, Roche, Lilly, Grunenthal, Gebro,, Paid instructor for: Lilly, Biogen, Speakers bureau: Biogen, Lilly, Pfizer, Grunenthal, Astropharma,, Galina Lukina Speakers bureau: Novartis, Pfizer, UCB, Abbvie, Biocad, MSD, Roche, Dan Nordstrom Consultant of: Abbvie, Celgene, Lilly, Novartis, Pfizer, Roche and UCB., Speakers bureau: Abbvie, Celgene, Lilly, Novartis, Pfizer, Roche and UCB., Karel Pavelka Consultant of: Abbvie, MSD, BMS, Egis, Roche, UCB, Medac, Pfizer, Biogen, Speakers bureau: Abbvie, MSD, BMS, Egis, Roche, UCB, Medac, Pfizer, Biogen, Manuel Pombo-Suarez Consultant of: Janssen, Lilly, MSD and Sanofi., Speakers bureau: Janssen, Lilly, MSD and Sanofi., Ziga Rotar Consultant of: Speaker and consulting fees from Abbvie, Amgen, Biogen, Eli Lilly, Medis, MSD, Novartis, Pfizer, Roche, Sanofi., Speakers bureau: Speaker and consulting fees from Abbvie, Amgen, Biogen, Eli Lilly, Medis, MSD, Novartis, Pfizer, Roche, Sanofi., Maria Jose Santos Speakers bureau: Novartis and Pfizer, Anja Strangfeld Speakers bureau: AbbVie, BMS, Pfizer, Roche, Sanofi-Aventis, Delphine Courvoisier: None declared, Axel Finckh Grant/research support from: Pfizer: Unrestricted research grant, Eli-Lilly: Unrestricted research grant, Consultant of: Sanofi, AB2BIO, Abbvie, Pfizer, MSD, Speakers bureau: Sanofi, Pfizer, Roche, Thermo Fisher Scientific

AB0273 PREDICTORS OF DRUG SURVIVAL OF bDMARDS IN BIO-NAIVE PATIENTS WITH RHEUMATOID ARTHRITIS (RA) DURING THE FIRST YEAR OF THERAPY.

Objectives:To investigate predictors of drug survival of bDMARDs in previously bio-naive patients (pts) with RA during the first year of therapy.Methods:204 adult bio-naive pts (173 women, 84.8%), with active RA, despite the concomitant DMARD therapy, were included into retrospective study. All of them initiated bDMARDs: infliximab (INF) - 65 pts (31.9%), rituximab (RTM) - 39 (19.1%), adalimumab (ADA) - 30 (14.7%), etanercept (ETA) - 28 (13.7%), abatacept (ABA) - 23 (11.3%), tocilizumab (TZ) - 15 (7.4%), certolizumab pegol - 4 (1.9%). The following indicators were used as survival predictors: sex, age and clinical form of RA. Pts were divided by age according to the classification adopted by the World Health Organization: 18-44 years (74 pts), 45-59 years (68 pts), 60-74 years (57 pts), 75 years or more (5 pts). Clinical forms of RA were presented: RA, seropositive by rheumatoid factor (RF), RA, seronegative by RF, RA with extra-articular manifestations, adult-oneset Still’s disease, juvenile RA. Predictors of therapy inefficiency or AE were investigated in Cox proportional risk model. Survival on drug was estimated using the Kaplan-Meier method and evaluation of difference significance using log-rank criterion.Results:A year later, 92 pts (45%) remained on bDMARDs and 112 pts had their treatment discontinued. The reasons of bDMARDs discontinuation during the first year of treatment were: lack of effectiveness (including primary inefficiency) - 50%, adverse events (AE) - 25%, administrative causes - 17%, remission - 6.25%, death due to reasons unrelated to the therapy - 1.75%. By the end of the observation period, the best survival was shown by RTM therapy (69.23% of patients continued treatment for a year), ETA (44.4% of patients) and ABA (43.48% of patients). Discontinuation of bDMARDs due to remission was achieved in 7 patients and proved to be significantly higher in the RTM group (10.26%, p &lt; 0.05) compared to the ABA group (8.7%) and ADA group (3.45%). Although the number of women continued after a year was significantly higher than that of men (84.8% and 15.2% respectively), female sex was not a reliable predictor of drug survival. At the same time, the rate of discontinuation due to AE in women was higher (96.55%, p = 0.03). After a year, the number of pts continuing treatment in all age groups remained comparable, and the difference between them - statistically not significant: 1 group (18-44 years old, 29 pts) - 31.52% of pts, 2 group (45-59 years old, 36 pts) - 39.13%, 3 group (60-74 years old, 26 pts) - 28.26%, 4 group (75-90 years old, 1 pts). Discontinuation of bDMARDs due to inefficiency was noted in 1 group more often (46.43%, 26 pts, р =0.03), in other groups this indicator was 33.93% (19 pts) in the 2nd group, 19.64% (11 pts) in the 3rd group and 0% in the 4th group. Discontinuation therapy due to AE was also prevalent in 1 group (50%, 14 pts) than in 2 (14.3%, 4 pts), 3 (32.1%, 9 pts) and 4 (3.6%, 1 pts). Discontinuation of therapy due to inefficacy was more common in the group of seronegative RA - 59.1% (p &lt; 0.05). In the seropositive RA group 24.8% of pts had interrupted bDMARDs for this reason, in the RA with extra-articular manifestations group it was 18.1%, in the adult-oneset Still’s disease group - 30% and in the juvenile RA group - 30%. Discontinuation of therapy due to remission was overwhelmingly observed in seropositive RA group (6 pts, 4%) and was significantly higher than in other groups (1 patient in RA with extra-articular manifestations group, 4.5%).Conclusion:Female sex, young age (18-44 years), RA, seronegative by RF were associated with less survival of bDMARDs due to lack of effectiveness and/or AE, and RTM and seropositive RA - with more frequency of discontinuation of therapy due to remission.Disclosure of Interests:Eugenia Aronova: None declared, Galina Lukina Speakers bureau: Novartis, Pfizer, UCB, Abbvie, Biocad, MSD, Roche, Galina Gridneva: None declared, Svetlana Glukhova: None declared, Anastasia Kudryavtseva: None declared

THU0095 IMPACT OF BASELINE EROSION SCORE ON RESPONSE TO TREATMENT AND FUTURE RADIOLOGICAL DAMAGE IN AVERT-2, A RANDOMISED PHASE IIIB STUDY OF ABATACEPT IN MTX-NAÏVE, ANTI-CITRULLINATED PROTEIN ANTIBODY–POSITIVE (ACPA+) PATIENTS WITH EARLY RA

Background: Bone erosions are associated with poor prognosis in patients (pts) with RA. They can be associated with subclinical inflammation and independently predict future radiological damage.1 The Phase IIIb Assessing Very Early RA Treatment (AVERT)-2 (NCT02504268) trial evaluated abatacept (ABA)+MTX in MTX-naive, ACPA+ pts with early RA.2 Objectives: To explore the impact of baseline (BL) X-ray erosion scores (ES) on clinical response and future radiological damage over 1 yr in different groups of pts from AVERT-2. Methods: BL and Wk 52 X-ray data were evaluated using Sharp/van der Heijde score. SDAI remission rates (RRs; ≤3.3), unadjusted mean changes from BL (CfB) and duration of/time to sustained remission over 52 wks were evaluated. Radiographic progression was assessed at Wk 52 using CfB in ES. A range of BL ES cut-offs were evaluated to highlight key findings through comparison of pts with low and high ES. Results: Of 994 pts in the study, 964 (97%) had BL (median 2.0, interquartile range [IQR] 0.5–5.1) and 792 (80%) had BL and Wk 52 (median 2.5, IQR 1.0–6.5) ES. Results in Table 1 are based on ES cut-offs of 2 and 5, resulting in 53% and 75%, respectively, of pts in low ES groups. In pts who received ABA+MTX, those with low ES had higher SDAI RRs over 52 wks vs pts with high ES. The relationship was more pronounced for higher cut-offs. This was not observed with ABA placebo+MTX (MTX). Greater reduction of mean CfB in SDAI was achieved in pts with high vs low ES who received ABA+MTX. This was not observed with MTX. Pts who received ABA+MTX had longer duration and shorter time to sustained SDAI remission vs MTX. With ABA+MTX, pts with low ES had longer duration and shorter time to sustained SDAI remission vs high ES. This was not observed with MTX. Mean CfB in ES at Wk 52 was lower in the ABA+MTX arm vs the MTX arm. ABA seemed to equally protect pts with low and high ES; with MTX, pts with high ES had higher mean CfB in ES at Wk 52 than pts with low ES. Conclusion: This erosion-based stratification of the AVERT-2 early seropositive RA population emphasizes the importance of treating pts prior to the accumulation of erosive disease. Abatacept+MTX led to higher SDAI RRs in pts with low vs high ES and provided further protection vs MTX alone against future radiological damage in pts with high ES. Additional statistical modelling and adjustment for confounding factors at BL is warranted.

Actual Persistence of Abatacept in Rheumatoid Arthritis: Results of the French-Ric Network.

Objectives: Data on abatacept (ABA) persistence in routine practice are limited. We aimed to study ABA persistence rates at 12 months, according to the date of initiation, and to analyze the factors associated with persistence at 12 months. Methods: We performed an observational, ambispective, multi-center study from January 2008 to July 2016, based on the French-RIC Network. We defined three groups of patients followed up for rheumatoid arthritis (RA), according to the date of initiation of ABA therapy: Group 1 (from 2007 to 31 July 2010: ABA indicated after anti-TNF failure); Group 2 (from 1 August 2010 to 31 March 2014: ABA indicated after conventional antirheumatic drugs failure); Group 3 (from 1 April 2014 to 1 July 2016: ABA available by the subcutaneous injection). Results: Among 517 patients who initiated ABA, drug persistence at 12 months was 68%. The only factor significantly associated with persistence rate at 12 months was C-reactive protein (CRP) < 10 mg/L at ABA initiation (odds ratio (OR) 0.6, 95% confidence interval 0.3–0.9; p = 0.0016). There was no significant difference in drug persistence according to date of initiation, the line of biological disease-modifying antirheumatic drugs (bDMARD) therapy or the route of administration. Conclusions: In routine practice, over time, ABA has come to be initiated earlier in the course of therapy for RA in France. Abatacept persistence is similar to that reported in the Orencia Rheumatoid Arthritis (ORA) registry, and does not differ according to the date of initiation. The only factor found to be associated with the persistence rate at 12 months was CRP < 10 mg/L at ABA initiation.

A Network Meta-Analysis to Compare Effectiveness of Baricitinib and Other Treatments in Rheumatoid Arthritis Patients with Inadequate Response to Methotrexate.

Background/ObjectivesThis article compares the effectiveness of baricitinib (BARI) 4 mg (oral, Janus kinase [JAK] 1/2 inhibitor) versus other targeted synthetic/biologic disease-modifying antirheumatic drugs, in combination with methotrexate (MTX), in moderate-to-severe rheumatoid arthritis patients with inadequate response (IR) to MTX.MethodsA systematic literature review was conducted to identify randomized controlled trials (RCTs) of the interventions of interest. Bayesian network meta-analyses (NMA) were used to compare American College of Rheumatology (ACR) responses at 24 weeks. A series of prespecified sensitivity analyses addressed the potential impact of, among others, baseline risk, treatment effect modifiers, and trial design on treatment response.ResultsNineteen RCTs were included in the NMA (primary analysis). For ACR20, BARI 4 mg + MTX was found to be more effective than adalimumab (ADA) 40 mg + MTX (Odds Ratio [OR] 1.33), abatacept (ABA) 10 mg + MTX (IV/4 weeks) (OR 1.45), infliximab (IFX) 3 mg + MTX (IV/8 wks) (OR 1.63), and rituximab (RTX) 1000 mg + MTX (OR 1.63). No differences were found on ACR50. For ACR70, BARI 4 mg + MTX was more effective than ADA 40 mg + MTX (OR 1.37), ABA 10 mg + MTX (OR 1.86), and RTX 1000 mg + MTX (OR 2.26). Sensitivity analysis including 10 additional RCTs with up to 20% of patients with prior biologic use showed BARI 4 mg + MTX to be more effective than tocilizumab (TCZ) 8 mg + MTX on ACR20 (OR 1.44). Results for all sensitivity analyses were consistent with the direction and magnitude of the primary results. Key limitations include the time span in which trials were conducted (1999–2017), during which patient characteristics and treatment approaches might have changed.ConclusionThis NMA suggests that BARI 4 mg + MTX is an efficacious treatment option in the MTX-IR population as evidenced by the robustness of results.

Drug retention of secondary biologics or JAK inhibitors after tocilizumab or abatacept failure as first biologics in patients with rheumatoid arthritis -the ANSWER cohort study.

The aim of this multicenter, retrospective study was to clarify the retention of secondary biological disease-modifying antirheumatic drugs (bDMARDs) or Janus kinase inhibitors (JAKi) in patients with rheumatoid arthritis (RA) who were primarily treated by tocilizumab (TCZ) or abatacept (ABT) as first bDMARDs. Patients who were treated by either TCZ (n = 145) or ABT (n = 76) and then switched to either tumor necrosis factor inhibitors (TNFi), TCZ, ABT, or JAKi (including only cases switched from TCZ) from 2001 to 2019 (female 81.0%, age 59.5years, disease duration 8.8years; rheumatoid factor positivity 75.4%; Disease Activity Score in 28 joints using C-reactive protein 3.7; concomitant prednisolone (PSL) dose 6.0mg/day (51.8%) and methotrexate (MTX) dose 8.0mg/week (56.1%); 81.9% discontinued first bDMARDs due to lack of effectiveness) were included. Drug retention and discontinuation reasons were estimated at 24months using the Kaplan-Meier method and adjusted for potential confounders by Cox proportional hazards modeling. Drug retentions for each of the reasons for discontinuation were as follows: lack of effectiveness in TCZ-switched group (TNFi (59.5%), ABT (82.2%), and JAKi (84.3%); TNFi vs. ABT; P = 0.009) and ABT-switched group (TNFi (79.6%) and TCZ (92.6%); P = 0.053). Overall retention excluding non-toxic reasons and remission for discontinuation were TNFi (49.9%), ABT (72.7%), and JAKi (72.6%) (TNFi vs. ABT; P = 0.017) in the TCZ-switched group and TNFi (69.6%) and TCZ (72.4%) (P = 0.44) in the ABT-switched group. Switching to ABT in TCZ-treated patients led to higher retention as compared with TNFi. Switching to TCZ in ABT-treated patients tended to lead to higher retention due to effectiveness, although total retention was similar as compared with TNFi. Key Point • This is the first retrospective, multi-center study aimed to clarify the retention rates of secondary bDMARDs or JAKi in patients with RA who were primarily being treated by TCZ or ABT as the first bDMARDs.

Abatacept no better than placebo for pSS.

Abatacept no better than placebo for pSS.

Safety and effectiveness of abatacept in systemic sclerosis: The EUSTAR experience

ObjectiveTo analyze the safety and effectiveness of abatacept (ABA) given in routine care to patients with systemic sclerosis (SSc). MethodsRetrospective multicenter observational study that enrolled patients with SSc treated with ABA. We collected epidemiological data and clinical outcomes. First, we analyzed the frequency of adverse effects. Secondly, we compared the evolution of different organ manifestations during ABA treatment. We collected data from 6 months before start of therapy to the last follow-up the following parameters: modified Rodnan Skin Score (mRSS), joints, lung and gastrointestinal involvement, concomitant medications, and laboratory tests. Results: Data on twenty-seven patients with SSc were collected (93% females; 67% limited SSc). Rheumatoid arthritis was the most frequent concomitant autoimmune disease. ILD was present in 15 patients. Anti-Scl 70 antibodies were present in 13 patients and rheumatoid factor and ACPA antibodies were present in eight and seven patients respectively. The main indication to use abatacept was joint involvement (59%) followed by myositis (26%). A total of 16 adverse effects were reported in 28 months of abatacept treatment including five that required hospitalization. Most of them occurred in the first 3 months after starting abatacept. After 12 months, the number of tender and swollen joints decreased compared to baseline (p<0.03 and p<0.02 respectively). Moreover, a beneficial effect of abatacept on HAQ-DI at 3 and 6 months (p<0.05) and on morning stiffness at 6 and 12 months (p<0.03) was observed. We also observed a decrease in the modified Rodnan skin score (p<0.05). No changes in lung or gastrointestinal involvement were found. Conclusions: ABA demonstrated a good safety profile and seems to have some effectiveness on joint involvement and related disability in SSc patients treated in routine care.

Safety of Abatacept in Italian Patients with Rheumatoid Arthritis and Interstitial Lung Disease: A Multicenter Retrospective Study.

Background: Treatment of rheumatoid arthritis (RA)-related interstitial lung disease (ILD) is challenging, and many conventional and biologic disease-modifying anti-rheumatic drugs (DMARDs) have been associated with ILD development or progression. The aim of this multicentric retrospective study was to analyze the evolution of ILD in Italian RA-ILD patients treated with abatacept (ABA). Methods: All RA-ILD patients treated with ABA for at least six months were retrospectively evaluated. Serology, previous and concurrent therapies, chest high-resolution computer tomography (HRCT), forced vital capacity (FVC), and lung diffusion of carbon monoxide (CO, DLCO) were collected. Results: Forty-four patients were included; HRCT, FVC, and DLCO were analyzed at baseline, at one year, and at the end of follow-up. A remission or a low disease activity of RA was reached in 41/44 patients. Overall, FVC and DLCO remained stable or increased in 86.1% and 91.7% of patients, respectively, while HRCT was stable or improved in 81.4% of them. Previous and concurrent treatments, in particular, methotrexate, serology, age, sex, joint and lung disease duration were not associated with the outcome at univariate analysis. Conclusion: The management of RA-ILD patients remains a critical unmet medical need. Waiting for prospective controlled studies, ABA has shown a good safety profile in our cohort of Italian RA-ILD patients.

Abatacept induced long-term non-progressive reduction in gamma-globulins and autoantibodies: dissociation from disease activity control.

To evaluate long-term effects on gamma-globulins and autoantibodies of abatacept (ABA) versus tumor necrosis factor inhibitors (TNFi) in rheumatoid arthritis (RA) patients. Eighteen RA patients undergoing abatacept (ABA-RA) and 18 age/sex-matched patients treated with TNFi (TNFi-RA) were compared regarding clinical data, total gamma-globulins (TGG), specific subtypes (IgG, IgM, IgA), free light chains (FLC), IgM/IgG rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP3), and anti-mutated citrullinated vimentin (anti-MCV), assessed before and every 6months, up to 24months. previous abatacept/rituximab or low TGG (< 0.7g/dL). At baseline, female sex (78 vs. 78%), age (55 vs. 53years), DAS28 (5.73 vs. 5.67), TGG (1.4 vs. 1.35g/dL), IgG (1168 vs. 1079mg/dL), IgM (107 vs. 113mg/dL), IgA (333 vs. 322mg/dL), kappa (342 vs. 249mg/dL), lambda (170 vs. 150mg/dL), IgM-RF (76 vs. 53UI), IgG-RF (63 vs. 25UI), anti-CCP3 (216 vs. 189UI), and anti-MCV (202 vs. 102UI) were comparable in ABA-RA and TNFi-RA (p > 0.05). Similar disease activity improvement was observed in both groups. In ABA-RA, significant decreases (p < 0.05) were observed in TGG (1.4 vs. 1.05g/dL), IgG (1168 vs. 997), IgA (333 vs. 278mg/dL), kappa (342 vs. 257mg/dL), lambda (170 vs. 144mg/dL), IgM-RF (76 vs. 37UI), IgG-RF (65 vs. 24UI), anti-CCP3 (216 vs. 183UI), and anti-MCV (202 vs. 60UI) at 6months, without further decreases. In contrast, TNFi-RA showed no decrease in any of such parameters. ABA-RA also had more often transient IgG levels under the lower limit of normality (66.7% vs. 33.3%, p = 0.046). No severe infection occurred. DAS28, ESR, and CRP correlated significantly to gamma-globulins and FLC at baseline (p < 0.05), but these correlations were longitudinally lost in ABA-RA, but not in TNFi-RA. ABA, but not TNFi, induces a safe, persistent, long-term, and non-progressive reduction in gamma-globulins and autoantibodies, including anti-MCV. This pattern is dissociated from disease activity control.Key Points• ABA induces a long-term and non-progressive reduction in gamma-globulins and FLC, which occurs regardless of disease activity control.• ABA-induced reduction in gamma-globulins and FLC promotes a dissociation of such parameters and disease activity.• The same pattern of reduction is observed in autoantibodies: IgM-RF, IgG-RF, anti-CCP3, and anti-MCV.• Low transient IgG can be observed in RA patients treated with ABA, but does not correlate to infection.

Better Retention of Abatacept Is Associated with High Rheumatoid Factor: A Five-Year Follow-Up Study of Patients with Rheumatoid Arthritis

Recently, biological disease-modifying antirheumatic drugs (bDMARDs) have revolutionized the treatment of rheumatoid arthritis (RA) and provided patients with a higher chance of achieving clinical remission. Among them, abatacept (ABT), which selectively inhibits T cell activation through blocking costimulation signal, has been reported efficacious in controlling disease activity. Previous studies have shown that ABT has a high retention rate of up to three years with tolerable adverse events; however, it remains unclear whether this is maintained in the longer term. Here we conducted a retrospective five-year follow-up study to explore prognostic factors concerning better retention. In total, 98 patients who were treated with ABT from May 2011 to July 2019 in Osaki Citizen Hospital were enrolled, including 73 female patients (74.5%). The Kaplan-Meier method was used to estimate the retention rate of ABT. The mean age of ABT initiation was 72.1 years. Concomitant methotrexate was prescribed for 39 patients, and ABT was used as the first-line bDMARD for 65 patients. Rheumatoid factor (RF) was positive in 79 patients. One-, three-, and five-year retention rates of ABT were 83.3%, 66.2%, and 62.7%, respectively. Approximately two-thirds of discontinuation resulted from an inadequate response. Multivariate logistic regression analysis revealed that positive RF was associated with better drug retention. Receiver operating characteristics analysis showed that patients with high RF (≥ 45 IU/mL) had better retention rate of ABT. In conclusion, ABT shows high retention rate among patients with positive RF. The present study may provide better insights when selecting bDMARDs.

Structure Prediction and Expression of Modified rCTLA4-Ig as a Blocker for B7 Molecules.

CTLA4-Ig (Abatacept) has been produced to suppress immune response by inhibition of T cells functions in autoimmune disease. A new drug, which is called belatacept, has recently been recently developed that is more efficient. The development has been occurred by two substitutions (A29Y, L104E) in the extracellular domain of CTLA4. In the present study, the bioinformatics analysis was used in order to make a new structure that has a better function in comparison with belatacept. Firstly, eight different structures were designed. Thereafter, the secondary and 3D structures, mRNA structure, docking of chimeric proteins with CD80/CD86, antigenicity and affinity of designed chimeric molecules were predicted. Based on the criteria, a new candidate molecule was selected and its gene synthesized. The gene was cloned and expressed in E. coli BL21 (DE3) successfully. The purified rCTLA4-Ig was analyzed by SDS-PAGE, western blotting, and ELISA. Circular dichroism analysis (CD analysis) was used for characterization of the rCTLA4-Ig. Affinity of rCTLA4-Ig was also evaluated by the flow cytometry method. Finally, its biological activity was determined by T cell inhibition test. The results showed rCTLA4-Ig and the belatacept protein have some similarities in structure and function. In addition, rCTLA4-Ig was able to bind CD80/CD86 and inhibit T cell function. Although flow cytomery results showed that the standard protein (CTLA4-Ig), represented better affinity than rCTLA4-Ig, the recombinant protein was able to inhibit T cell proliferation as well as CTLA4-Ig.