Yi Hu

Objective: To explore health-related quality of life (HRQOL) measured by the 36-item Short Form Health Survey (SF-36), SF-36 physical component summary (PCS), SF-36 mental component summary (MCS), and Short Form 6D (SF-6D) in adults with juvenile idiopathic arthritis (JIA) compared to patients with rheumatoid arthritis (RA) and the general population. Methods: We used 6-month follow-up data from the Norwegian Disease-Modifying Antirheumatic Drug Register (NOR-DMARD), including adult patients with JIA and RA starting or switching disease-modifying antirheumatic drug (DMARD) treatment. Age- and gender-adjusted regression analyses were used to compare outcomes among JIA, RA, and the general Norwegian population. Results: Register data were available for 232 patients with JIA and 2764 with RA at 6 months follow-up. Patients with JIA had poorer physical health compared to those with RA (adjusted difference [95% CI]: PCS −3.58 [−6.09 to −1.08]). Compared to the general population, PCS scores were lower in both JIA and RA (adjusted differences [95% CI]: JIA–general population −15.70 [−18.21 to −13.19], RA–general population −12.12 [−12.76 to −11.47]). Mental health measured by MCS was similar across the 3 groups. Average SF-6D utility levels were comparable in JIA and RA, but lower than in the general population. Similar proportions of patients with JIA and RA experienced improvements exceeding minimum clinically important difference (MCID) in SF-36 scale scores, PCS, MCS, and SF-6D after 6 months. Conclusion: Compared to patients with RA and the general population, patients with JIA had lower physical HRQOL 6 months after DMARD initiation. Mental health composite scores were similar among patients with JIA, those with RA, and the general population. Both disease groups showed similar levels of improvement with treatment.

Background Lack of response to TNF-inhibitors (TNFi) can be caused by subtherapeutic drug levels and anti-drug antibodies (ADAb). Therapeutic-drug-monitoring (TDM) can help clinicians tailor treatment and may improve effectiveness, safety and cost-effectiveness of TNFi. For TDM to be validated as a clinical tool, therapeutic ranges must be identified. Objectives To explore the association between adalimumab serum drug level, treatment response and drug survival in patients with inflammatory arthritis, with the intention to identify a therapeutic range. In addition, to assess frequency and clinical implications of ADAb formation. Methods Patients with a clinical diagnosis of rheumatoid arthritis (RA), spondyloarthritis (SpA) or psoriatic arthritis (PsA) starting treatment with adalimumab and enrolled in the observational NOR-DMARD study were included. Treatment response at 3 months was defined as EULAR good or moderate response in RA/PsA and ASDAS Major or Clinically Important Improvement in SpA. Serum drug levels and ADAb at 3 months were measured using an in-house fluorescence method, with ADAb measured in patients with serum drug levels < 3mg/L. Comparisons of serum drug level and ADAb formation between diagnosis groups was done by Mann-Whitney U and χ2 test, respectively. Multivariate logistic regression analyses were used to assess serum drug level and treatment response and Cox proportional hazard regression analyses were used to assess drug survival and serum drug level, ADAb formation and methotrexate use, all analyses adjusted for age, sex and previous use of bDMARDs. Results A total of 343 patients (98 RA, 70 PsA, 177 SpA) were included (median age 46.0 years [SD 14.1], 182 [53%] female). 123/340 (36%) patients used methotrexate as co-medication. The median serum drug level at 3 months was 7.3 mg/L (IQR 3.7-10.3) and 34 (10 %) patients developed ADAb, these findings were comparable across diagnoses, (Figure 1A). Serum drug levels at 3 months were higher in responders (7.8 mg/L [IQR 5.4-10.5]) than in non-responders (6 mg/L [IQR 2.6-9.6]), p=0.0014. Percent distribution of responders at 3 months stratified by serum adalimumab levels by percentile distribution suggested that the therapeutic ranges were 6 -12 mg/L for RA/PsA and >1.4 mg/L SpA, with no upper cut-off detected in SpA, (Figure 1B and C). RA and PsA patients with serum adalimumab > 6 mg/L had higher odds for response to therapy at 3 months (Odds Ratio [OR] 2.2 [95% CI 1.1 – 4.5], p=0.026), and lower treatment discontinuation rate (Hazard Ratio [HR] 0.43 [95% CI 0.27-0.80], p= 0.006). No additional benefit was found with serum drug levels >12 mg/L. SpA patients with serum adalimumab level >1.4 mg/L had higher odds for response (OR 4.7 [95% CI 1.4-15], p=0.01) Further, in these patients treatment discontinuation was seen at a lower rate (HR 0.35 [95% CI 0.17-0.73], p= 0.005). Patients with ADAb at 3 months discontinued treatment at a higher rate (HR 3.4 [95% CI 2.1-5.3], p=Conclusion This study is the first to explore associations between adalimumab serum levels and clinical outcomes across all inflammatory arthritides. Higher adalimumab drug levels were associated with clinical response at 3 months and long-term drug survival. This study suggests 6 - and 1.4 mg/L as lower target adalimumab levels for RA/PsA and SpA respectively and contributes to the development of TDM algorithms for adalimumab in arthritis patients. Serum adalimumab levels at 3 months. A) Violin plot. Each data point is a participant, and the solid orange line show the group median. B) and C) Percent distri bution of responders at 3 months stratified by serum adalimumab levels. Adalimumab groups are divided by percentile distribution. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests Ingrid Jyssum: None declared, Johanna Elin Gehin: None declared, Eirik kristianslund: None declared, Joseph Sexton: None declared, David Worren: None declared, Yi Hu Speakers bureau: Boehringer, Tore K. Kvien Speakers bureau: Grünenthal, Sandoz, UCB, Consultant of: AbbVie, Amgen, Celltrion, Gilead, Novartis, Pfizer, Sandoz, UCB, Grant/research support from: AbbVie, Amgen, BMS, Galapagos, Novartis, Pfizer, UCB, Espen A Haavardsholm Speakers bureau: Pfizer, UCB, Consultant of: AbbVie, Boehringer- Ingelheim, Eli Lilly, Gilead, Nils Bolstad: None declared, Silje Watterdal Syversen: None declared, Guro Løvik Goll Speakers bureau: AbbVie/Abbott, Galapagos, Pfizer, UCB., Consultant of: AbbVie/Abbott, Galapagos, Pfizer, UCB.

Background: The significantly prognostic value of fibrinogen-to-albumin ratio (FAR) has been proved in patients with coronary artery disease and different oncologic disorders. This study aimed to investigate the predictive value of FAR for left ventricular systolic dysfunction (LVSD) in acute coronary syndromes (ACS) patients. Methods: A total of 650 ACS patients after percutaneous coronary intervention (PCI) were eventually enrolled in the analysis. Participants were classified into three groups according to baseline FAR levels (T1: FAR < 73.00; T2: 73.00 ≤ FAR < 91.00; T3: FAR ≥ 91.00). The association between FAR and LVSD was assessed by binary logistic regression analysis. A nomogram to predict the risk of LVSD was constructed based on the output indices from multivariate regression analyses. Results: Patients with LVSD showed significantly higher FAR, monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) than those without. FAR was an independent predictor of left ventricular dysfunction from the multivariate analyses (OR, 1.038; 95%CI, 1.020–1.057; P < 0.001). The area under receiver operating characteristic curve (AUC) of FAR predicting the occurrence of LVSD was 0.735. Meanwhile, FAR was the most powerful predictor than MLR, NLR, and PLR. Nomogram with the AUC reaching 0.906 showed a robust discrimination. Conclusions: Admission FAR is independently and significantly associated with LVSD in patients with ACS undergoing PCI.

Objective: To compare the effectiveness of tumor necrosis factor inhibitors (TNFi) ± comedication and methotrexate (MTX) monotherapy between patients with adult juvenile idiopathic arthritis (JIA) and patients with rheumatoid arthritis (RA).Methods: Adult patients with JIA and RA were identified from the Norwegian Antirheumatic Drug Register (NOR-DMARD) register. Disease activity measurements at baseline, 3, 6, and 12 months were compared between patients with JIA and RA starting (1) TNFi and (2) MTX monotherapy, using age- and gender-weighted analyses. We calculated differences between JIA and RA in mean changes in Disease Activity Score in 28 joints (DAS28), Clinical Disease Activity Index (CDAI), and Simplified Disease Activity Index (SDAI), among other disease activity measures. DAS28, CDAI, SDAI, and American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) remission rates at 3, 6, and 12 months, as well as 6- and 12-month Lund Efficacy Index (LUNDEX)-corrected rates, were calculated.Results: We identified 478 patients with JIA (TNFi/MTX monotherapy, n = 358/120) and 4637 patients with RA (TNFi/MTX monotherapy, n = 2292/2345). Patients with JIA had lower baseline disease activity compared to patients with RA across treatment groups. After baseline disease activity adjustment, there were no significant differences in disease activity change from baseline to 3, 6, and 12-months of follow-up between patients with JIA and RA for either treatment group. Twelve-month remission rates were similar between groups based on DAS28 (TNFi: JIA 55.2%, RA 49.5%; MTX monotherapy: JIA 45.3%, RA 41.2%) and ACR/EULAR remission criteria (TNFi: JIA 20.4%, RA 20%; MTX monotherapy: JIA 17%, RA 12.7%). Median drug survival (yrs) was similar for JIA and RA in both treatment groups (TNFi: JIA 1.2, RA 1.4; MTX monotherapy: JIA 1.3, RA 1.6).Conclusion: TNFi and MTX monotherapy are effective in adult JIA, with similar effectiveness to that shown in RA.