Background:Upadacitinib (UPA), an oral JAK inhibitor selective for JAK1, demonstrated efficacy in patients (pts) with moderate to severe rheumatoid arthritis (RA) with an inadequate response (IR) to csDMARDs or bDMARDs in the SELECT-NEXT1 and SELECT-BEYOND2 trials, respectively.Objectives:To investigate the speed of response to UPA across disease measures in csDMARD- and bDMARD-IR pts.Methods:661 pts in NEXT and 498 in BEYOND received UPA 15 mg or UPA 30 mg once daily (QD) or placebo (PBO) for 12 weeks (wks)1,2. Time to first achievement of clinically meaningful outcomes, including ACR20/50, DAS28-CRP≤3.2 and Low Disease Activity (LDA) measures of CDAI (≤10) and SDAI (≤11) was evaluated. The cumulative incidences of ACR20/50, DAS28-CRP≤3.2 and LDA by CDAI and SDAI over 12 wks were estimated. Hazard ratios between UPA and PBO were obtained using Cox proportional hazards model with treatment group, corresponding baseline values and main stratification factors, without control for multiple comparisons. All analyses were based on observed data without imputation.Table 1Summary of Median Time (in Weeks) to Achieve First Response Over 12 WeeksHR, hazard ratio, NE (not estimatable) indicates that the response was not reached within the 12-week period. ***p<0.001Results:Pts had a disease duration of 7 and 13 years in NEXT and BEYOND respectively.1,2 In BEYOND, pts were treatment-refractory as evidenced by 53% having received ≥2 prior bDMARDs2. Median times to achieve ACR20 were similar, irrespective of pt population, being 4 wks for UPA 15 mg QD and 2–3 wks for UPA 30 mg QD vs 12 wks on PBO (p<0.001). In general, the median times to achieve ACR50 and DAS28-CRP≤3.2 for UPA 15 mg and 30 mg QD were ~12 wks and ~8 wks for both csDMARD-IR and bDMARD-IR pts, whereas the median was not reached for pts on PBO during the first 12 wks (p<0.001, table 1). The median time to LDA by CDAI and SDAI was ~12 wks across UPA doses and populations, but was not reached for pts receiving PBO within that time. Pts receiving UPA were 2–4 times more likely to achieve clinical responses vs pts receiving PBO. In general, both UPA doses performed similarly across pt populations, with numerically quicker responses observed in pts receiving UPA 30 mg vs UPA 15 mg QD. Median times to achieve 20% and 50% improvements in tender and swollen joint counts were 1–2 wks and 2–4 wks respectively, for both UPA doses, irrespective of pt population. Median times to achieve 20% improvements in morning stiffness duration and severity were approximately 2 wks in each of the UPA arms vs 4 wks on PBO (p<0.001).Conclusions:Pts receiving UPA at either 15 mg or 30 mg QD were more likely to achieve clinical responses at significantly earlier time points when compared with pts receiving PBO. Irrespective of being csDMARD-IR or bDMARD-IR, times to achieve various clinical responses were consistent between pt populations.References[1]Burmester, et al. Arthritis Rheumatol2017;69S10.[2]Genovese, et al. Arthritis Rheumatol2017;69S10.Acknowledgements:AbbVie: Study sponsor, study...

Background:Upadacitinib (UPA), an oral, JAK1-selective inhibitor, demonstrated efficacy through 12 and 24 weeks (wks) in phase 3 trials of patients (pts) with active rheumatoid arthritis (RA) and inadequate response (IR) to csDMARDs and bDMARDs, respectively.1,2 Efficacy evaluations at Wk 12 are an important assessment point according to T2T recommendations.3 Objectives:To assess the impact of UPA at 12 wks on individual and composite measures of RA disease activity.Methods:Pts received UPA 15 mg or 30 mg once daily (QD) or PBO for 12 wks in two phase 3 trials. SELECT NEXT1 and SELECT BEYOND2 enrolled csDMARD- and bDMARD-IR pts, respectively. For this investigation, responses at Wk 12, were defined as ≥50% improvement in ACR components. Among ACR50 responders, the proportions of pts achieving ≥50% improvement in all 7 components of the ACR response criteria [Tender Joint Count (TJC68), Swollen Joint Count (SJC66), Pt Global Assessment (PtGA), Physician Global Assessment (PhGA), Pt Pain, Health Assessment Questionnaire-Disability Index (HAQ-DI), and high sensitive C-reactive protein (hsCRP)] were assessed. Differences in the cumulative distributions of CDAI, DAS28-CRP, and SDAI between baseline (BL) and Wk 12 were assessed. All analyses were based on observed data without imputation.Results:Pts in both studies, on average, had established, moderate to severe RA at BL, with (mean) disease durations of 7.3 and 13.2 years, CDAI of 38.2 and 40.9, in csDMARD-IR and bDMARD-IR pts, respectively; 53% of bDMARD-IR pts had exposure to ≥2 bDMARDs.1,2 In both populations, significantly more pts on UPA vs PBO achieved ≥50% improvement in each ACR component at Wk 12 (Table). Among pts who achieved ACR50 at Wk 12, approximately one-half of the csDMARD-IR and one-third of the bDMARD-IR pts achieved ≥50% improvement in all 7 ACR components. While there were no differences at BL, cumulative distributions of CDAI, DAS28-CRP, and SDAI separated by treatment at Wk 12 (p<0.001); for the lowest quartiles for UPA 15 mg and 30 mg vs PBO, CDAI levels dropped to 6.2 and 5.1 vs 12.5 in csDMARD-IR; and 7.2 and 8.2 vs 13.1 in bDMARD-IR.Conclusions:In pts with an insufficient response to either csDMARDs or bDMARDs, treatment responses at 12 wks were observed in significantly higher proportions with UPA vs PBO. Favorable effects with UPA were seen in the composite scores and the individual parameters, including PROs and acute-phase reactants.References[1]Burmester, et al., Arthritis Rheumatol2017;69:S10.[2]Genovese, et al. Arthritis Rheumatol2017;69:S10.[3]Smolen, et al. 2015. doi:10.1136/annrheumdis-2015-207524Acknowledgements:AbbVie Inc was the study sponsor, contributed to study design, data collection, analysis & interpretation, and to writing, reviewing, and approval of final version. Medical writing support was provided by Naina Barretto, PhD, of AbbVie, Inc.Disclosure of Interest:R. van Vollenhoven Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Pfizer, Roche, and UCB, Consultant for: AbbVie, AstraZeneca,...

BackgroundLow trough levels of the tumour necrosis factor inhibitor, adalimumab (ADL), and anti-ADL antibodies (AAA) were reported to be correlated with lack of response at later time points in patients (pts) with rheumatoid arthritis (RA).1 ObjectivesTo assess the ability of ADL trough levels and clinical assessments at Week 12 to predict clinical remission (REM) after 24 weeks (wks) of treatment with ADL ±methotrexate (MTX) in established RA pts.MethodsData from MTX inadequate responders (MTX-IR) pts with established RA with available measurement of ADL trough levels and clinical assessments at Wks 12 and 24 from several clinical trials were pooled: for pts who received ADL+MTX combination therapy from DE009, DE019, M10–261 and M13–390; for pts who received ADL monotherapy from DE011, M10–261 and M13–390. Efficacy endpoints at Wk 24 were DAS28-CRP<2.6 and DAS28-CRP low disease activity (LDA,<3.2), remission (REM) and LDA by simplified disease activity index (SDAI,≤3.3 and≤11 respectively); REM and LDA by clinical disease activity index (CDAI,≤2.8 and≤10 respectively). Each of the pooled datasets was randomly and equally split into training and testing sets. Predictive modelling was performed on the training set, and the best-performing model was selected and validated in the testing set. The performance of the final model was reported based on the testing set.ResultsBased on the cutoffs selected by the predictive model, ADL concentrations at Wk 12 were only slightly predictive for Wk 24 clinical assessment in the ADL monotherapy group, but not in the ADL+MTX group (table 1). However, based on achievement of the specified CDAI, SDAI or DAS28-CRP score at Wk 12 (selected by the model), pts were correctly predicted to reach Wk 24 REM or LDA with an accuracy of 80%–90% and area under the receiver operating characteristic curve (AUC) of 75%–90% (table 2). As an example, pts on ADL monotherapy with DAS28 <3.3 at Wk 12 had 60% and 70% chance of reaching Wk 24 DAS28-CRP<2.6 and LDA respectively, whereas pts with DAS28 ≥3.3 had 0% and 7% chance of achieving Wk 24 DAS28-CRP<2.6 and LDA, respectively (table 1). Pts on ADL+MTX with Wk 12 SDAI<12.5 had a 25% and 77% chance of achieving SDAI REM and LDA at Wk 24, respectively.Abstract THU0185 – Table 1ConclusionsThe ADL concentrations at Week 12 selected by the prediction model were weak predictors of disease control at 6 months, especially for pts on ADL+MTX combination therapy. However, using the model-selected cutoffs of composite clinical endpoints at Wk 12, disease control after 6 months of ADL±MTX treatment could be correctly predicted in 70%–80% of pts.References[1] Jani, et al. Arthritis & Rheumatol2015.[2] Huang X, et al. Statistics in Medicine2017.AcknowledgementsAbbVie Inc was the study sponsor, contributed to study design, data collection, analysis and interpretation, and to writing, reviewing, and approval of final version. Medical writing support was provided by Naina Barretto, PhD, of AbbVie, Inc.Disclosure of InterestJ. Smolen Grant/research support from: AbbV...

Objective This study was performed to evaluate the effectiveness of social platform-based continuity of care in improving cognitive and prognostic effects of young age diabetic patients without diabetic retinopathy (DR). Methods A total of 88 young age diabetic patients admitted to the outpatient clinic of First Affiliated Hospital of Soochow University (Endocrine and Ophthalmology Outpatient) from January 2021 to May 2022 were recruited and assigned via random number table method to receive either routine follow-up care (routine group) or social platform-based continuity of care (WeChat group), with 44 patients in each group. Treatment compliance, cognitive-behavioral ability, self-care ability (self-care responsibility, self-care skills, self-status, knowledge of diabetic retinopathy), quality of life (physical function, psychosocial, symptom and visual function, social activity), and prognosis of the patients were analyzed to investigate the effectiveness of WeChat social platform-based continuity of care. All patients were followed up for one year. Results Patients receiving WeChat social platform-based continuity of care exhibited obviously higher treatment compliance and better cognitive-behavioral ability, self-care responsibility, self-care skills, self-state, and diabetic retinopathy knowledge follow-up than those with routine care (P<0.05). Patients in the WeChat group had significantly better physical function, mental psychology, symptoms and visual function, and social activity levels than those in the routine group (P<0.05). WeChat-based continuity of care resulted in a significantly lower incidence of visual acuity loss and diabetic retinopathy during follow-up than routine care (P<0.05). Conclusion WeChat social platform-based continuity of care effectively improves treatment compliance and diabetic retinopathy awareness, and enhances self-care ability of young patients with diabetes mellitus. The life quality of these patients is improved and the risk of poor prognosis has been reduced.

BackgroundEnthesitis, a key pathology in axial spondyloarthritis (axSpA), has been difficult to treat with conventional therapies and may take longer to resolve than other disease manifestations. It is unknown if failure to attain resolution of enthesitis affects achievement of normal quality of life (QoL) and clinical response.ObjectivesTo assess if enthesitis at baseline (BL) and after 12 wks of adalimumab (ADA) treatment in the ABILITY-3 study associates with achieving normal QoL and clinical response in patients (pts) with non-radiographic axSpA (nr-axSpA).MethodsABILITY-3 enrolled adult pts with nr-axSpA with objective evidence of inflammation (MRI positive or elevated hsCRP), active disease at BL (ASDAS ≥2.1, BASDAI≥4, and Patient‘s Assessment of Total Back Pain score ≥4), and an inadequate response to ≥2 NSAIDs. Pts received ADA 40 mg every other wk during a 28-wk open-label lead-in. Pearson’s correlation coefficients were used to assess the relationship between total enthesitis count (sum of Maastricht Ankylosing Spondylitis Enthesitis Score [MASES] and plantar fascia enthesitis score) and QoL and disease activity at BL. Multivariable stepwise logistic regression was used to evaluate the relationship between total enthesitis count or enthesitis location and normal QoL (EQ-5D≥0.898 or SF36 MCS/PCS≥50) and clinical response (ASDAS-ID [ASDAS <1.3], ASAS40, or BASDAI50) at wk 12.ResultsAt BL, 74% (501/673) of pts had enthesitis, and mean (95% CI) total enthesitis count was 3.7 (3.42, 3.98). Enthesitis resolved in 39% (196/501) of pts, and total enthesitis count was 1.9 (1.68, 2.12) at wk 12 of ADA treatment. At BL, total enthesitis count significantly correlated with all QoL and disease activity measures (Table). Each 1-unit increase in BL total enthesitis count was associated with 7% lower odds of ASDAS-ID (OR [95% CI]; 0.93 [0.88, 0.99], p=0.018) and 6% lower odds of BASDAI50 (0.94 [0.89, 0.99], p=0.024) at wk 12 and was not associated with normal QoL or ASAS40 at wk 12. Total enthesitis count at wk 12 was associated with lower odds of normal QoL and clinical response at wk 12 (Table). Achievement of normal QoL at wk 12 was less likely if pts had BL enthesitis at the posterior (EQ-5D≥0.898) or anterior superior iliac spine (SF36 PCS ≥50), and pts with BL enthesitis at the 7th costochondral joint were less likely to achieve clinical response at wk 12 (Table).Abstract SAT0294 – Table 1Association of Total Enthesitis Count With QoL and Disease Activity at BL and Clinical Response at Wk 12Conclusions39% of pts achieved complete resolution of enthesitis after 12 wks of ADA treatment. Total enthesitis count at BL was not associated with normal QoL and inversely associated with clinical response at wk 12. Total enthesitis count at wk 12 was negatively associated with normal QoL and clinical response. Our exploratory analysis suggested possible inverse associations of specific BL enthesitis sites with achievement of normal QoL and clinical response; however, additional research is needed to further define these rela...