Low starting dosage of infliximab with possible escalating dosage in psoriatic arthritis gives the same treatment results as standard dosage of adalimumab or etanercept: results from the nationwide Icelandic ICEBIO registry

Objective: To explore differences in response to a low dosage regimen of infliximab with an escalating dosage in comparison to a standard dosage of etanercept and adalimumab in patients with psoriatic arthritis (PsA). Methods: Biologically naïve PsA patients who were beginning anti-TNF-α therapy were selected from the ICEBIO registry. Demographics and clinical differences were compared in four treatment groups: infliximab 4 mg/kg; etanercept or adalimumab at baseline and on follow-up (6 and 12 months, last visit). The Kruskal–Wallis rank sum test was used for comparison of the groups and the Wilcoxon test to compare the two infliximab dosage regimens. Results: One hundred and eighty-five patients (61% female) were identified; 84 patients received infliximab, 66 etanercept, and 35 adalimumab. A total of 19% of the patients treated with infliximab escalated their dosage ≥4 mg/kg. No significant differences were observed at baseline in respect to visual analog scale (VAS) pain, VAS fatigue, Health Assessment Questionnaire, C-reactive protein (CRP), numbers of swollen or tender joints, or Disease Activity Score (DAS) 28-CRP values. A similar treatment response was observed in all four treatment groups on follow-up. Conclusion: In respect to treatment effects, a low dosage of infliximab with possible escalating dosage is acceptable for the majority of PsA patients who are in need of biological treatment.The study was partly funded by a study grant from The Icelandic Society for Rheumatology.Peer Reviewe

A novel knee prosthesis model of implant-related osteo- myelitis in rats

Background and purpose: There have been numerous reports of animal models of osteomyelitis. Very few of these have been prosthesis models that imitate human conditions. We have developed a new rat model of implant-related osteomyelitis that mimics human osteomyelitis, to investigate the pathology of infection after orthop edic implant surgery. Methods: 2 wild-type strains of Staphylococcus aureus, MN8 and UAMS-1, and their corresponding mutants that are unable to produce poly-N-acetyl glucosamine (PNAG) (ica::tet) were injected into the medullary canals of the femur and tibia at 3 different doses: $10^2$, $10^3$, and > $10^4$ CFU/rat. We measured clinical signs, inflammatory markers, radiographic signs, histopathology, and bacteriology in the infected animals. Results: An inoculum of at least $10^4$ cfu of either wild-type bacterial strain resulted in histological, bacteriological, and radiographic signs of osteomyelitis with loosening of the prosthesis. An inoculum of $10^3$ CFU gave signs of osteomyelitis but the prosthesis remained in situ. Bacterial inocula of $10^2$ cfu gave no signs of osteolysis. Interpretation: We have established a new knee prosthesis model that is suitable for reliable induction of experimental implant-associated osteomyelitis with the prosthesis in situ, using a small inoculum of S. aureus. At a dose of $10^3$ CFU/rat, bacteria unable to produce PNAG (ica::tet) had only minor defects in their virulence

Patients with psoriatic arthritis who are not eligible for randomised controlled trials for TNF inhibitors have treatment response and drug survival similar to those who are eligible.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadOBJECTIVES: To determine in a retrospective cohort whether patients with psoriatic arthritis (PsA) who would not have fulfilled the inclusion criteria for randomised controlled trials (RCTs) for the TNF inhibitor (TNFi) chosen for their treatment (excl) have similar benefits and drug survival as those patients who would have (incl). METHODS: All patients with rheumatic disorders who are treated with biological disease-modifying antirheumatic drugs in Iceland are registered in ICEBIO. On 1 February 2016, 329 individuals with PsA were registered in ICEBIO, of whom 231 had data available for their first start of TNFi and could be evaluated according to the inclusion criteria of the respective RCTs. Disease activity was collected at baseline using Visual Analogue Scale (pain, fatigue and global (patient and physician) assessments), swollen joint count (SJC) and tender joint count (TJC), Disease Activity Score 28-joint count C reactive protein (DAS28-CRP) and Health Assessment Questionnaire (HAQ). Treatment response was measured at 6 and 18 months according to American College of Rheumatology response criteria, DAS28-CRP and Disease Activity Score in Psoriatic Arthritis for 28 joints. Drug survival rate was also analysed. RESULTS: The demographics of these two groups were similar at baseline, although the incl group had higher SJC (5.5 vs 3.8) and subsequently higher DAS28-CRP (4.6 vs 4.2). While a larger change in disease activity was observed in the incl group with respect to HAQ and SJC, both groups had similar disease activity at follow-up. Drug survival was similar in both groups. CONCLUSIONS: Patients with PsA who would not have fulfilled the inclusion criteria in RCTs reach similar disease activity scores at follow-up of 6 and 18 months and have similar drug survival as those patients who would have been included in RCTs.NordForsk University Hospital, Reykjavik, Iceland Society for Rheumatology of Icelan

Impact of different infliximab dose regimens on treatment response and drug survival in 462 patients with psoriatic arthritis: results from the nationwide registries DANBIO and ICEBIO.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.The aim of this study was to describe dose regimens, dose escalation and clinical outcomes in TNF-α inhibitor (TNFi)-naive patients with PsA treated with infliximab in routine rheumatology care.We conducted an observational cohort study based on the nationwide Danish Rheumatologic Database (DANBIO) and Center for Rheumatology Research (ICEBIO) registries. Stratified by country, characteristics of patients treated with ≤3 mg infliximab/kg body weight, 3-5 mg/kg or ≥5 mg/kg every 8 weeks were described. Outcomes were evaluated by ACR 20%, 50% and 70% (ACR20/50/70) responses and European League Against Rheumatism good response after 6 months, disease activity after 12 months, Kaplan-Meier plots and regression analyses.Four hundred and sixty-two patients (376 Danish, 86 Icelandic) received treatment with infliximab. In Danish patients, the starting dose was ≤3 mg/kg in 110 patients (29%), 3-5 mg/kg in 157 (42%), ≥5 mg/kg in 38 (10%) and unregistered in 71 (19%). In Icelandic patients, corresponding numbers were 64 (74%), 17 (27%), 0 (0%) and 5 (6%). Patients with a higher body weight received lower doses per kilogram. Danish patients received higher doses than Icelandic patients at baseline [median 3.1 (interquartile range 3.0-3.8) vs 2.3 (2.1-2.9) mg/kg, P 70% of Icelandic and Danish PsA patients treated with infliximab received sustained doses below the 5 mg/kg every 8 weeks recommended in international guidelines. Lower starting doses did not affect drug survival or response

Infliximab biosimilar-to-biosimilar switching in patients with inflammatory rheumatic disease:clinical outcomes in real-world patients from the DANBIO registry

OBJECTIVE: Successful uptake of biosimilars in rheumatology is limited by lack of real-world evidence regarding effectiveness of biosimilar-to-biosimilar switching. We investigated infliximab biosimilars CT-P13-to-GP1111 switching among patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (AxSpA). METHODS: Observational cohort study from the DANBIO registry. Patients were classified as originator-naïve or originator-experienced. Retention rates of 1-year GP1111 treatment were explored (Kaplan-Meier). We identified baseline factors (at the time of switch) associated with withdrawal of GP1111 (multivariable Cox-regression analyses with HRs including originator treatment history). Changes in subjective and objective measures of disease activity 4 months before and after the switch were assessed in individual patients. RESULTS: Of 1605 patients (685 RA, 314 PsA and 606 AxSpA, median disease duration was 9 years, 37% in Clinical Disease Activity Index/Ankylosing Spondylitis Disease Activity Score remission), 1171 were originator-naïve. Retention rates at 1-year were 83% (95% CI: 81% to 85%) and 92% (95% CI: 90% to 95%) for the originator-naïve and originator-experienced, respectively. GP1111 retention rates were higher in originator-experienced compared to originator-naïve with RA (HR=0.4 (95% CI: 0.2 to 0.7)) and PsA (HR=0.2 (95% CI: 0.1 to 0.8)), but not significantly for AxSpA: HR=0.6 (95% CI: 0.3 to 1.2). Lower disease activity was associated with higher retention. Changes in disease activity preswitch and postswitch were close to zero. CONCLUSION: This real-world observational study of more than 1600 patients with inflammatory arthritis showed high 1-year retention following a nationwide infliximab biosimilar-to-biosimilar switch. Retention was higher in originator-experienced and in patients with low disease activity, suggesting outcomes to be affected by patient-related rather than drug-related factors

Treatment retention of infliximab and etanercept originators versus their corresponding biosimilars : Nordic collaborative observational study of 2334 biologics naive patients with spondyloarthritis

Objective Although clinical trials support equivalence of originator products and biosimilars for etanercept and infliximab, real-world studies among biologics-naive patients with spondyloarthritis (SpA) are lacking. The objectives were to compare treatment retention in biologics-naive patients with SpA starting either the originator product or a biosimilar of infliximab and etanercept, and to explore the baseline characteristics of these patients. Methods Patients with SpA (ankylosing spondylitis/non-radiographical axial SpA/undifferentiated SpA), starting infliximab or etanercept as their first-ever biological disease-modifying antirheumatic drug during January 2014-June 2017 were identified in five Nordic biologics-rheumatology registers. Baseline characteristics were retrieved from each registry; comorbidity data were identified through linkage to national health registers. Country-specific data were pooled, and data on infliximab and etanercept were analysed separately. Comparisons of treatment retention between originators and biosimilars were assessed through survival probability curves, retention rates (2 years for infliximab/1 year for etanercept) and Hazard Ratios (HR). Results We included 1319 patients starting infliximab (24% originator/76% biosimilar), and 1015 patients starting etanercept (49% originator/51% biosimilar). Baseline characteristics were largely similar for the patients treated with the originators compared with the corresponding biosimilars. Survival probability curves were highly similar for the originator and its biosimilar, as were retention rates: infliximab 2-year retention originator, 44% (95% CI 38% to 50%)/biosimilar, 46% (95% CI: 42% to 51%); and etanercept 1-year retention originator, 66% (95% CI 61% to 70%)/biosimilar, 73% (95% CI 68% to 78%). HRs were not statistically significant. Conclusion This observational study of biologics-naive patients with SpA from five Nordic countries showed similar baseline characteristics and very similar retention rates in patients treated with originators versus biosimilars, for both infliximab and etanercept, indicating comparable effectiveness in clinical practice.Peer reviewe

Second and third TNF inhibitors in European patients with axial spondyloarthritis: Effectiveness and impact of the reason for switching

OBJECTIVE: To investigate real-world effectiveness of tumor necrosis factor inhibitors (TNFi) in patients with axial spondyloarthritis (axSpA) and the association with 1) treatment line (second and third TNFi-series) and 2) reason for withdrawal from the preceding TNFi (lack of efficacy (LOE) versus adverse events (AE)). METHODS: Prospectively collected routine care data from 12 European registries were pooled. Rates for 12-month drug retention and 6-month remission (Ankylosing Spondylitis Disease Activity Score C-reactive protein inactive disease (ASDAS-ID)) were assessed in second and third TNFi-series and stratified by withdrawal reason. RESULTS: We included 8254 s and 2939 third TNFi-series; 12-month drug retention rates were similar (71%). Six-month ASDAS-ID rates were higher for the second (23%) than third TNFi (16%). Twelve-month drug retention rates for patients withdrawing from the preceding TNFi due to AE versus LOE were similar for the second (68% and 67%) and third TNFi (both 68%), while for the second TNFi, rates were lower in primary than secondary non-responders (LOE < 26 versus ≥26 weeks) (58% versus 71%, p< 0.001). Six-month ASDAS-ID rates for the second TNFi were higher if the withdrawal reason was AE (27%) versus LOE (17%), p< 0.001, while similar for the third TNFi (19% versus 13%, p= 0.20). CONCLUSION: A similar proportion of axSpA patients remained on a second and third TNFi after one year, but with low remission rates for the third TNFi. Remission rates on the second TNFi (but not the third) were higher if the withdrawal reason from the preceding TNFi was AE versus LOE