No abstract

IL‐17‐producing T cells (Th17 cells) are believed to contribute to local inflammation and joint damage in rheumatoid arthritis (RA). Limited data exist on Th17 cells located within the inflamed synovial tissue (ST) of patients with RA. Here, we aimed to generate polyclonal T cell lines (TCLs) from the RA ST and assess their cytokine production, including the effects of exogenous IL‐15 on IL‐17 production in vitro. For five patients with RA, polyclonal TCLs were established from ST obtained by joint surgery. Synovial TCLs were expanded and stimulated by anti‐CD3/CD28 microbeads and exogenous cytokines. Cytokine production was assessed by culture supernatant analyses and intracellular flow cytometry, and TCLs were sorted based on their surface expression of CCR6. In addition to IL‐17, we detected IL‐6, IL‐10, IFN‐γ and TNF‐α in the synovial TCL culture supernatants. Exogenous IL‐15 increased the production of IL‐17 as well as the other cytokines except IFN‐γ. For IL‐17, this effect was more pronounced after prolonged culture times. Intracellular flow cytometry confirmed the presence of IL‐17+ and IL‐17+IFN‐γ+ CD4+ T cells in the TCLs. IL‐17+ and IL‐17+IFN‐γ+ T cells were enriched in the CD4+CCR6+ population. In conclusion, Th17 cells can be detected after polyclonal expansion and stimulation of RA synovial TCLs generated by joint surgery. The Th17 cells from the RA ST were enriched in the CD4+CCR6+ population, and they were sensitive to exogenous IL‐15. Th17 cells present within the synovial compartment may contribute to the RA pathogenesis and local joint damage.

BackgroundThe NOR-SWITCH study is a 52-week randomized, double-blind, non-inferiority, phase IV switch trial in patients with Crohn's disease (CD), ulcerative colitis (UC), spondyloarthritis (SpA), rheumatoid arthritis (RA), psoriatic arthritis (PsA) and plaque psoriasis (Ps) on stable treatment with originator infliximab (Remicade®, INX), funded by the Norwegian government. Previously, primary analyses of the pooled indications have been published1.ObjectivesTo investigate efficacy, safety and immunogenicity in SpA patients treated with continuous INX vs patients switched to CT-P13 (biosimilar infliximab, Remsima®) in the NOR-SWITCH study (explorative analyses).MethodsPatients were randomized 1:1 to continued INX or switch to CT-P13. Serum drug levels were analyzed by automated in-house assay. The primary endpoint was disease worsening according to disease-specific composite measures and/or consensus between investigator/patient. Exploratory subgroup analyses examined disease worsening and safety in SpA. The primary endpoint was analysed by logistic regression, adjusted for diagnosis and disease duration.ResultsDemographics, occurrence of disease worsening, change in disease measures and treatment-emergent adverse events (TEAE) were similar (Table), as were serum drug levels for INX and CT-P13 (Figure).Table 1.Demographics, baseline characteristics (FAS), percentage of patients with disease worsening, change in disease measures during 52 weeks follow-up (PPS)Demographics, baseline characteristicsINXCT-P13 Total number of SpA patients PPS/FAS43/4542/46Age (years) mean (SD)50.0 (10.3)52.8 (10.8)Females7 (16%)8 (17%)Duration of ongoing INX treatment (years) mean (SD)8.6 (3.1)8.7 (3.2)Immunosuppressive co-medication15 (33%)10 (22%)HLA B27 pos31 (94%)33 (87%)Disease worsening95% CI of group difference after 52 weeks All study patients53 (26.2%)61 (29.6%)-12.7–3.9% SpA17 (39.5%)14 (33.3%)-14.5–27.2%Change in disease measures from baseline Physician Global Assessment of Disease Activity (0–10)-0.1 (1.4)-0.5 (1.3)0.53–0.53 Patient Global Assessment of Disease Activity (0–10)0.1 (2.2)-0.4 (1.8)-0.08–0.62 Log10 erythrocyte sedimentation rate (mm/h)0.0 (0.3)-0.0 (0.3)-0.14–0.06 Log10 C-reactive protein (mg/L)-0.0 (0.4)-0.1 (0.4)-0.11–0.15 ASDAS0.1 (0.6)-0.2 (0.7)-0.27–0.24 BASDAI0.3 (1.0)-0.2 (1.4)-0.50–0.47TEAE (FAS)116102Data are n (%), mean (SD) or median (25–75 percentiles). 95% CI, 95% confidence interval of the adjusted treatment difference. BASDAI, Bath Ankylosing Spondylitis Disease Activity Index. ASDAS, Ankylosing Spondylitis Disease Activity Score. FAS, Full Analysis Set. PPS, Per Protocol Set. TEAE, treatment emergent adverse events.ConclusionsExplorative analyses in the NOR-SWITCH study showed similar efficacy, drug levels and safety in SpA patients switched to CT-P13 as those on continuous INX. The study was not powered to show non-inferiority within each diagnosis.References Jørgensen KK et al. Switching from originator infliximab to biosimilar CT-P13 compared to maintained treatment with originator inflixim...

BackgroundThe NOR-SWITCH study was a 52-week randomized, double-blind, non-inferiority, phase IV switch trial in patients with Crohn's disease (CD), ulcerative colitis (UC), spondyloarthritis (SpA), rheumatoid arthritis (RA), psoriatic arthritis (PsA) and plaque psoriasis (Ps) on stable treatment with originator infliximab (Remicade®, INX) and was funded by the Norwegian government. Previously, the primary analyses of the pooled indications have been published1.ObjectivesTo investigate efficacy, safety and immunogenicity in RA patients treated with continous INX vs patients switched to CT-P13 (biosimilar infliximab, Remsima®) in the NOR-SWITCH study (explorative analyses).MethodsPatients were randomized 1:1 to continued INX or switch to CT-P13. Serum drug levels were analysed in automated in-house assay. The primary endpoint was disease worsening according to disease-specific composite measures and/or consensus between investigator/patient leading to major treatment change. Exploratory subgroup analyses examined disease worsening and safety in RA. The primary endpoint was analysed using logistic regression, adjusted for diagnosis and disease duration.ResultsDemographics, occurence of disease worsening, change in disease measures and treatment-emergent adverse events (TEAE) were similar (Table). Serum drug levels for INX and CT-P13 were similar throughout the study (Figure)Table 1.Demographic and baseline characteristics (FAS), percentage of RA patients with disease worsening and change in disease measures during 52 weeks follow-up (PPS)Demographics and baseline characteristicsINXCT-P13 Total number of RA patients PPS/FAS30/3930/38Age (years) mean (SD)59.9 (11.5)60.4 (11.4)Females31 (79%)25 (66%)Duration of ongoing infliximab treatment (years) mean (SD)8.2 (3.7)9.9 (3.4)Concomitant immunosuppressive medication27 (69%)34 (89%)ACPA pos25 (83%)20 (74%)Disease worsening95% CI of group difference after 52 weeks All study patients53 (26.2%)61 (29.6%)-12.7–3.9% RA11 (36.7%)9 (30.0%)-20.3–29.3%Change in disease measures from baseline Physician Global Assessment of Disease Activity (0–10)-0.1 (1.3)0.1 (1.4)-0.58–0.68 Patient Global Assessment of Disease Activity (0–10)1.1 (1.4)0.4 (1.9)0.21–1.91 Log10 erythrocyte sedimentation rate (mm/h)0.0 (0.3)0.0 (0.3)-0.08–0.16 Log10 C-reactive protein (mg/L)0.1 (0.3)0.0 (0.5)-0.11–0.22 DAS280.2 (0.9)0.2 (0.9)-0.30–0.50TEAE (FAS)9462Data are n (%), mean (SD) or median (25–75 percentiles). 95% CI, 95% confidence interval of the adjusted treatment difference. DAS28, Disease Activity Score in 28 joints. FAS, Full Analysis Set. PPS, Per Protocol Set. TEAE, treatment emergent adverse events.ConclusionsExplorative analyses in the NOR-SWITCH study showed similar efficacy, serum drug levels and safety in RA patients switched to CT-P13 as those on continuous INX. The study was not powered to show non-inferiority within each diagnosis.References Jørgensen KK et al Switching from originator infliximab to biosimimlar CT-P13 compared to maintained treatment with originator infliximab (NOR-SWITCH):...

among participants using observed variables, was used to differentiate "pain phenotypes" considering sex, body mass index (BMI), emotional problems, comorbidities, number of painful sites and knee structural damage on MRI. Results: Three pain phenotypes were identified: Class 1: high levels of emotional problems and low levels of structural damage (24%); Class 2: high levels of structural damage and low levels of emotional problems (20%); Class 3: relatively low levels of emotional problems and low levels of structural damage (56%). People within Class 1 were more likely to be female, had greater BMI, lower education level, more comorbidities, more severe knee pain and more painful sites as compared to Class 2 and Class 3. Furthermore, WOMAC pain scores and number of painful sites were consistently greater at baseline, 2.6, 5.1 and 10.7 years in Class 1 than Class 2 and Class 3 (all P<0.05).