H Ahmad

SAT0468 Presence of poor prognostic factors may predict response to abatacept in patients with active psoriatic arthritis: results from a post hoc analysis from a phase iii study

Background Abatacept, a selective T-cell co-stimulation modulator, significantly increased ACR20 response and had an overall beneficial effect on musculoskeletal symptoms in patients (pts) with active psoriatic arthritis (PsA) in the Phase III Active pSoriaTic athritis RAndomizEd triAl (ASTRAEA, NCT01860976).1 Factors that may predict responses to abatacept were explored in this post hoc analysis. Objectives To evaluate the relationship between baseline characteristics and abatacept response in a post hoc analysis of ASTRAEA. Methods Pts were randomized (1:1) to SC abatacept 125 mg weekly or placebo for 24 weeks in this trial. Pts without >20% improvement in joint counts at Week 16 were switched to open-label abatacept (early escape). ACR20 response rate in pts stratified by baseline variables was investigated in a multivariate analysis and odds ratios (ORs) generated to identify differences in response. Using a cut-off of OR 1.2, indicating pt subgroups in whom abatacept appeared to have a meaningful treatment benefit, baseline variables were further investigated in a univariate analysis and estimated differences calculated. Results Of 424 pts enrolled, 213 received abatacept and 211 placebo. In abatacept-treated pts, the multivariate model showed a difference in ACR20 response (OR >1.2) for baseline CRP (>upper limit of normal [ULN] vs ≤ULN; OR 1.346 [95% CI 0.668, 2.712]), DAS28 (CRP) (>5.1 vs ≤5.1; 1.489 [0.782, 2.836]), dactylitis (>0 vs 0; 1.372 [0.708, 2.659]), and median baseline erosions (≥3 vs <3; 1.924 [1.032, 3.587]). In placebo-treated pts, the OR was >1.2 for dactylitis only (1.406 [0.619, 3.193]). These factors, which have been identified previously as indicating poor prognosis in PsA, were balanced between treatment arms at baseline. In the univariate model by poor prognostic factors, the differences in ACR20 response rates with abatacept treatment vs placebo in distinct subgroups were numerically greater in pts who were positive for these prognostic factors at baseline than in those who were not (Figure). Conclusions These findings identified subgroups of pts with PsA with certain baseline characteristics in whom abatacept is most likely to be effective. The predictive factors identified are aligned with poor prognostic factors in the EULAR and Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) guidelines,2,3 and may indicate pts with the highest unmet medical need. References Mease P, et al. Arthritis Rheumatol 2016;68(Suppl 10):[Abstract 1041]. Gossec L, et al. Ann Rheum Dis 2016;75:499–510. Coates L, et al. Arthritis Rheumatol 2016;68:1060–71. Disclosure of Interest P. Mease Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, Pfizer, Sun, UCB, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Crescendo Biosciences, Corrona, Demira, Janssen, Lilly, Novartis, Pfizer, Sun, UCB, Zynerba, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Crescendo Biosciences, Genentech, Janssen, Novartis, Pfizer, UCB, I. McInnes Grant/research support from: Bristol-Myers Squibb, Celgene, Janssen, UCB, Consultant for: Bristol-Myers Squibb, Celgene, Janssen, Novartis, Pfizer, AbbVie, UCB, V. Strand Consultant for: AbbVie, Amgen Corporation, AstraZeneca, Biogen Idec, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Celltrion, Corrona, Crescendo Biosciences/Myriad Genetics, EMD Serono, Genentech/Roche, GlaxoSmithKline, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Samsung, Sandoz, Sanofi, UCB, O. FitzGerald Grant/research support from: AbbVie, Pfizer, Bristol-Myers Squibb, Consultant for: AbbVie, Pfizer, Bristol-Myers Squibb, Celgene, Janssen, Novartis, UCB, Lilly, H. Ahmad Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, A. Johnsen Employee of: Bristol-Myers Squibb, Celgene, Janssen, Novartis, Pfizer, AbbVie, UCB, J. Ye Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, S. Banerjee Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb

Comparative evaluation of treatment patterns and healthcare utilization of newly-diagnosed rheumatoid arthritis patients by anti-cyclic citrullinated peptide antibody status

Abstract Background: Anti-cyclic citrullinated peptide (CCP) antibody positivity is an established diagnostic factor for severe disease activity and joint damage and a prognostic factor for aggressive disease in rheumatoid arthritis (RA). Objective: To compare RA-related treatment, healthcare utilization, and joint erosion between anti-CCP-positive and anti-CCP-negative RA patients. Methods: Newly-diagnosed RA patients were identified from the Henry Ford Health System database between January 1, 2009 and December 31, 2014; the date of the first RA diagnosis within the study period was the index date. Baseline anti-CCP test was used to categorize patients as anti-CCP-positive or anti-CCP-negative, and outcomes were evaluated in the 6 months post-index. Results: There were 217 anti-CCP-positive and 191 anti-CCP-negative RA patients included in the study. A higher proportion of anti-CCP-positive patients were initiated on RA treatment than anti-CCP-negative patients (70.5% vs 23.0%; p < .0001). More anti-CCP-positive patients received methotrexate (73.2% vs 56.8%; p = .0374), while more anti-CCP-negative patients received hydroxychloroquine (31.8% vs 13.1%; p = .0037) in first-line therapy. A higher proportion of anti-CCP-negative patients were tested for rheumatoid factor (RF) and erythrocyte sedimentation rate (ESR). Of those tested, there were more positive test results in the anti-CCP-positive cohort compared to the anti-CCP-negative cohort (RF: 84.4% vs 18.2%, p < .0001; C-reactive protein [CRP]: 69.7% vs 48.3%, p = .0008; and ESR: 89.5% vs 53.9%, p < .0001). Outpatient utilization predominated, with more anti-CCP-positive patients having any outpatient physician office visit (96.3% vs 77.5%, p < .0001) and a higher mean number of visits (5.3 vs 2.5, p < .0001) than anti-CCP-negative patients. Among anti-CCP-positive (n = 113) and anti-CCP-negative (n = 58) patients with imaging results, more anti-CCP-positive patients had joint erosion compared to anti-CCP-negative patients (18.6% vs 8.6%; p = .0858); however, statistical significance was not reached. Conclusion: RA patients with positive anti-CCP antibodies had higher degrees of inflammation and disease activity as indicated by laboratory results, which likely contributed to their higher rates of healthcare utilization, joint erosion, and proportions of RA treatment.

The Effectiveness of fMRI Data when Combined with Polygraph Data

Abstract The Integrated Zone Comparison Technique (IZCT) was utilized with computerized polygraph instrumentation and the Academy for Scientific Investigative Training’s Horizontal Scoring System ASIT PolySuite algorithm, as part of a blind study in the detection of deception. This paper represents a synergy analysis of combining fMRI only deception data with each of the three individual physiological parameters that are used in polygraph. They include the electro-dermal response (EDR), pneumo, and cardio measurements. In addition, we compared the detection accuracy analysis using each single parameter by itself. The fMRI score and each individual polygraph parameter score on individual subjects were averaged to establish an overall score.

AB0291 Identification of joint locations that are poor prognostic indicators and require more intensive therapy in an early, rapidly progressing ra cohort: a post hoc agree analysis

Background Patients (pts) with early RA often present with multiple areas of involvement. Limited data exist to identify which specific joints or joint locations may be indicative of poorer prognosis and require more intensive initial therapy.1 Objectives This analysis investigated which joint locations have the poorest prognosis and compared clinical response rates between abatacept (ABA)+MTX and MTX monotherapy by baseline (BL) swollen joint status for specific joint locations. Methods Data from AGREE (NCT00122382), a double-blind Phase III study of ABA+MTX (n=256) vs MTX (n=253) in biologic-naïve pts with early (≤2 years [yrs]) erosive RA, were analysed by BL swollen joint status (present, absent) for 8 different joint locations: hands, wrists, elbows, shoulders, jaw, knees, ankles and feet. Overall characteristics and study results were reported previously.2 Swelling was evaluated at BL and after 6 months (mths) of treatment. Differences between treatment groups in clinical response endpoints (i.e. DAS28 [CRP]<2.6, SDAI≤3.3, CDAI≤2.8, Boolean and HAQ remission ≤0.5 at 6 mths) and swelling resolution at 6 mths were assessed by BL swollen joint status, for each joint location. Results In an early RA cohort of pts at risk of active, rapidly progressing disease, the proportions of pts (n=509) with a swollen joint at BL were 99% hand, 92% wrist, 79% ankle, 69% knee, 66% foot, 48% elbow, 34% shoulder and 9% jaw. Pts with a swollen jaw (n=45) had more tender joints (mean [SD] 40.0 [15.1] vs 30.1 [14.1]), more swollen joints (35.9 [13.3] vs 21.1 [9.5]), higher total Sharp score (9.4 [10.1] vs 6.9 [9.1]) and longer disease duration (11.7 [9.2] yrs vs 6.0 [6.9] yrs) than those without jaw swelling (n=464). Higher HAQ-DI was seen in pts with a swollen knee or shoulder (1.8 [0.6] vs 1.5 [0.7] and 1.9 [0.6] vs 1.6 [0.7], respectively). Presence of BL synovitis was not associated with greater BL anti-citrullinated protein antibodies or RF positivity, probably due to the inclusion of mainly seropositive pts. In general, absence of BL swelling was associated with higher clinical response at 6 mths, both for ABA+MTX and MTX. Independent of BL swollen joint status, ABA+MTX had higher clinical response rates (DAS28, SDAI, CDAI, Boolean and HAQ remission) than MTX, except for the non-swollen wrist. Overall mean Boolean remission rates were 13.7% for ABA+MTX vs 5.5% for MTX with difference in proportions (95% CI) of 8.1% (2.6, 13.7) (p=0.003). The largest difference in Boolean remission rate (95% CI) favouring ABA+MTX was 9.6% (4.2, 15.1) (p<0.001) in pts with a swollen wrist at BL (figure 1). Difference in swollen joint resolution between ABA+MTX and MTX was most pronounced for pts with a swollen hand (mean [95% CI]: 42.7% [36.7, 48.8] vs 27.9% [22.4, 33.4], respectively).Abstract AB0291 – Figure 1 Treatment Group Comparisons of Boolean Remission Rates in Pts with BL Swollen Joint by Joint Location (Proportion [95% CI]). Conclusions BL swelling in the shoulder, knee and jaw is associated with a more severe RA profile. Remission rates were higher with ABA+MTX than MTX when BL swelling was present, especially in the wrist. Also, swollen joint resolution was more pronounced with ABA+MTX, especially in the hands. References [1] Bergstra SA, et al. RMD Open2017;3:e000568. [2] Westhovens R, et al. Ann Rheum Dis2009;68:1870–7. Disclosure of Interest P. Durez Speakers bureau: Bristol-Myers Squibb, Eli Lilly, Sanofi, S. Robert Employee of: Bristol-Myers Squibb, A. Thiry Employee of: Bristol-Myers Squibb, H. Ahmad Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb

SAT0108 Efficacy of abatacept versus adalimumab on the proportion of patients with seropositive, erosive early ra achieving das28 (CRP) <2.6 or validated measures of remission: a post hoc analysis of the 2-year ample trial

Background Binary cut-offs for disease activity are frequently used in clinical decision-making for patients with RA because they are accurate reflections of disease activity, discriminate well between disease acvitiy states and are feasible to perform in routine clinical practice.1 Results from a previous post hoc analysis of the randomized, controlled, head-to-head AMPLE trial (NCT00929864) indicated a trend for increased efficacy, as assessed using DAS28 (CRP), for abatacept (ABA) compared with the TNF inhibitor adalimumab (ADA) in patients with seropositive, erosive early RA.2,3 Objectives To evaluate post hoc the impact of treatment with either SC ABA or ADA on sustained validated definitions of remission and DAS28 (CRP) <2.6 in patients with seropositive, early, rapidly progressing RA with inadequate response to MTX. Methods This post hoc analysis of the AMPLE trial builds on previous work3 to compare clinical outcomes between treatment groups in two subsets: patients with disease duration ≤6 months, RF or anti-citrullinated protein antibody seropositivity and >1 radiographic erosion (Cohort 1), and patients in whom ≥1 of these inclusion criteria were absent (Cohort 2). Disease activity and patient-reported outcomes were evaluated at Weeks 26, 52 and 104. Endpoints were defined as percentages of patients with DAS28 (CRP) <2.6, SDAI ≤3.3, CDAI <2.8 or Boolean remission. Endpoints were compared between ABA and ADA treatment groups using chi-square tests. Results Of 646 randomized patients, 83 were included in Cohort 1 (ABA, n=38; ADA, n=45) and 563 in Cohort 2 (ABA, n=280; ADA, n=283). At Week 52, significantly more ABA- than ADA-treated patients achieved DAS28 (CRP) <2.6 in Cohort 1 (p=0.03), a trend that was not seen at Week 104 or in Cohort 2 at either time point. At Weeks 52 and 104, more ABA- than ADA-treated patients achieved CDAI, SDAI and Boolean remission in Cohort 1, a trend not seen in Cohort 2. Figure 1 Comparison of Treatments by Sustained Remission Outcomes and DAS28 (CRP) <2.6A) Cohort 1: Pts with early (<6 months disease duration) seropositive erosive RA. B) Cohort 2: Pts with the absence of any 1 factor in Cohort 1. All p>0.05 unless otherwise stated. *Boolean remission is defined as tender joint count ≤1, swollen joint count ≤1, CRP≤1 mg/dL and patient global assessment ≤1 (on a 0-10 scale). Conclusions This post hoc analysis indicates a trend towards increased efficacy for abatacept compared with adalimumab on measures of sustained remission and DAS28 (CRP) <2.6 in patients with seropositive, erosive early RA. These results, along with results from other studies,4,5 support the pursuit of a clinically definable subset of patients who may respond differentially to targeted therapies. References: [1] Anderson J, et al. Arthritis Care Res (Hoboken) 2012;64:640-7. [2] Schiff M, et al. Ann Rheum Dis 2014;73:86-94. [3] Fleischmann R, et al. EULAR 2017; poster SAT0041. [4] Harrold LR, et al. J Rheumatol 2018;45:32-9. [5] Emery P, et al. Ann Rheum Dis 2015;74:19-26. Disclosure of Interest: R. FleischmannGrant/research support from: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene, EMD-Serono, Eli Lilly, Merck, Novartis, Pfizer, Roche, Sanofi-Genzyme, UCB, Consultant for: AbbVie, ACEA, Amgen, Bristol-Myers Squibb, GSK, Eli Lilly, Novartis, Pfizer, Sanofi-Genzyme, UCB, M. Weinblatt Grant/research support from: Bristol-Myers Squibb, Amgen, Crescendo Bioscience, Sanofi, Consultant for: Bristol-Myers Squibb, Amgen, Crescendo Bioscience, AbbVie, Eli Lilly, Pfizer, Roche, Merck, Samsung, Novartis, H. Ahmad Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, M. Maldonado Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, E. Alemao Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Y. Elbez Consultant for: Bristol-Myers Squibb, M. Schiff Consultant for: Abbvie, Bristol-Myers Squibb, Eli Lilly, Johnson & Johnson, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb

FRI0513 Validating Mri-Detected Inflammation Thresholds Predictive of Structural Damage Progression in Patients with Rheumatoid Arthritis in A Randomized Placebo-Controlled Trial

Background In rheumatoid arthritis (RA), the concept that subclinical inflammation causes damage progression is now well established, but there is little work on how much inflammation is safe.1 A previous study established RA MRI Scoring (RAMRIS) synovitis and osteitis thresholds (≤3 each and ≤9 [≤3 plus 2*≤3] as a total inflammation score) that correlated with a low risk of structural damage progression.2 Further validation of these thresholds may guide physicians in clinical practice more reliably to identify individuals with a low likelihood of structural damage progression. Objectives To validate the performance of RAMRIS synovitis, osteitis and combined total inflammation thresholds in the prediction of structural damage progression.1 Methods AVERT (Assessing Very Early Rheumatoid arthritis Treatment) was a Phase IIIb, randomized, active-controlled, 24-month trial, with a 12-month, double-blind treatment period. Patients with early RA received abatacept + MTX, abatacept monotherapy or MTX. Contrast-enhanced MRIs of the dominant hand and wrist were performed. MRI data were pooled from all three treatment arms (intent-to-treat population) for this post hoc analysis. Inflammation (synovitis, osteitis and combined) and erosion were scored by two central readers at baseline, Month 6 and Month 12. Structural damage progression was defined as erosion change >0.5. Patients were stratified into “low” and “not low” risk groups for MRI structural progression based on their inflammation scores at the start of the observation period: low: ≤3 for synovitis, ≤3 for osteitis and ≤9 when combined (with osteitis double-weighted due to its strong correlation with progression), as suggested by Baker et al.2 Log odds ratio of probability of progression were compared between subgroups. Results 351 patients were randomized and treated, with MRIs at baseline; 276 (78.6%) and 235 (67.0%) also had MRI data available at Month 6 and Month 12, respectively. The percentage of patients with structural damage progression at follow-up was significantly higher in the “not low” versus “low” risk subgroup for all comparisons (Table). The probability of progression from Month 6 to Month 12 was significantly lower among patients with synovitis score ≤3, osteitis score ≤3, and total inflammation score ≤9 at Month 6. Conclusions The applied inflammation thresholds distinguished between patients with RA at lower or higher risk of structural damage progression, validating the previously proposed thresholds. This provides further support for the clinical value of measuring inflammation via MRI, as well as its role in predicting structural damage progression. References Gandjbakhch F, et al. J Rheumatol 2014;41:398–406. Baker J, et al. Arthritis Rheumatol 2015; 67(Suppl 10):S832. Disclosure of Interest H. A. Ahmad Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, J. F. Baker: None declared, M. Østergaard Grant/research support from: AbbVie, Bristol-Myers Squibb, Janssen, Merck, Speakers bureau: AbbVie, Bristol-Myers Squibb, Boehringer-Ingelheim, Celgene, Eli Lilly, Centocor, GSK, Hospira, Janssen, Merck, Mundipharma, Novartis, Novo, Orion, Pfizer, Regeneron, Schering-Plough, Roche, Takeda, UCB, Wyeth, J. Ye Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, P. Emery Grant/research support from: AbbVie, Merck, Pfizer, Roche, Consultant for: AbbVie, Bristol-Myers Squibb, Merck, Pfizer, Roche, Lilly, Novartis, Samsung Bioepis, P. G. Conaghan Consultant for: AbbVie, Lilly, Novartis, Pfizer, Speakers bureau: AbbVie, Janssen, Roche