Publications by authors named "Tore K Kvien"

344 Publications

Incidence, sociodemographic factors and treatment penetration of rheumatoid arthritis and psoriatic arthritis in Norway.

Semin Arthritis Rheum 2021 Oct 20;51(5):1081-1088. Epub 2021 Aug 20.

Division of Rheumatology and Research, Diakonhjemmet Hospital, Diakonveien 12, Oslo 0370, Norway.

Objectives: To evaluate nationwide incidence, sociodemographic associations and treatment penetration of rheumatoid arthritis (RA) and psoriatic arthritis (PsA) in Norway.

Methods: The study combined data from nationwide registries on the total Norwegian adult population (age ≥ 18). From the Norwegian Patient Registry, incident RA and PsA cases during 2011-2015 were identified with records of first and second healthcare episodes listing RA/PsA diagnostic codes, and ≥ 1 episode in an internal medicine or rheumatology unit with RA/PsA code during the two-year period after the first episode. Dispensed DMARD prescriptions were obtained from the Norwegian Prescription Database. Persons with dispensed DMARD prescriptions or biologic DMARDs given in hospitals > 12 months before the index date were excluded.

Results: Incidence of RA/PsA in Norway was 42/26 per 100,000 person-years (55/28 among women and 28/23 among men). RA peak incidence was observed at ages 70-79 in both sexes, whereas the peak incidence of PsA occurred at ages 50-59. Age- and sex-standardized incidences of RA and PsA were lower among persons with higher education levels. Within a year from the index date, 82.4/57.4% of RA/PsA patients used synthetic DMARDs while 9.4/9.5% used biologic DMARDs.

Conclusions: Register-based incidence estimates for RA and PsA in Norway are similar to other Nordic countries, but slightly higher than in previous Norwegian studies. Furthermore, we found that higher socioeconomic status was associated with lower incidence of both RA and PsA. Although conventional synthetic DMARDs were less often used in early PsA than RA, frequency of biologic DMARD prescriptions was comparable.
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http://dx.doi.org/10.1016/j.semarthrit.2021.08.006DOI Listing
October 2021

Fatigue in patients with early rheumatoid arthritis undergoing treat-to-target therapy: predictors and response to treatment.

Ann Rheum Dis 2021 Aug 13. Epub 2021 Aug 13.

Division of Rheumatology and Research, Diakonhjemmet Hospital, Oslo, Norway.

Objectives: Fatigue is a frequent symptom in rheumatoid arthritis (RA) and has high impact on quality of life. We explored associations between disease activity and fatigue in patients with early RA during the initial 24 months of modern treat-to-target therapy and predictors of fatigue after 24 months of follow-up.

Methods: Data were obtained from the treat-to-target, tight control Aiming for Remission in Rheumatoid Arthritis: a Randomised Trial Examining the Benefit of Ultrasound in a Clinical Tight Control Regime (ARCTIC) trial. Fatigue was measured on a visual analogue scale (VAS) from 0 to 100 mm and defined as clinically relevant if VAS was ≥20 mm. Baseline predictors of fatigue at 24 months were analysed by multivariable logistic regression.

Results: 205 patients with fatigue data at baseline and 24 months were included. Median (25th, 75th percentiles) symptom duration was 5.4 months (2.8, 10.4), fatigue VAS 37.0 mm (13.0, 62.0) and mean Disease Activity Score (DAS) 3.4 (SD 1.1) at baseline. Prevalence of fatigue declined from 69% at baseline to 38% at 24 months. Fewer swollen joints (OR 0.92, 95% CI 0.87 to 0.98, p=0.006), lower power Doppler ultrasound score (OR 0.95, 95% CI 0.90 to 0.99, p=0.027) and higher patient global assessment (PGA) (OR 1.03, 95% CI 1.01 to 1.04, p<0.001) increased the risk of clinically relevant fatigue at 24 months. Not achieving remission at 6 months was associated with a higher risk of reporting fatigue at 24 months.

Conclusions: Fatigue in patients with early RA was prevalent at disease onset, with a rapid and sustained reduction during treatment. Low objective disease activity and high PGA at baseline were predictors of clinically relevant fatigue at 24 months.
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http://dx.doi.org/10.1136/annrheumdis-2021-220750DOI Listing
August 2021

Two-year reduction of dual-energy CT urate depositions during a treat-to-target strategy in gout in the NOR-Gout longitudinal study.

Rheumatology (Oxford) 2021 Jul 10. Epub 2021 Jul 10.

Division of Rheumatology and Research, Diakonhjemmet Hospital, Oslo, Norway.

Objectives: There is a lack of large longitudinal studies of urate deposition measured by dual-energy computed tomography (DECT) during urate lowering therapy (ULT) in people with gout. We explored longitudinal changes in DECT urate depositions during a treat-to-target strategy with ULT in gout.

Methods: Patients with a recent gout flare and serum-urate (sUA) >360 µmol/l attended tight-control visits during escalating ULT. The treatment target was sUA <360 µmol/l, and <300 µmol/l if presence of tophi.A DECT scanner (General Electric Discovery CT750 HD) acquired data from bilateral forefeet and ankles at baseline and after one and two years. Images were scored in known order, using the semi-quantitative Bayat method, by one experienced radiologist who was blinded to serum urate and clinical data. Four regions were scored: the first metatarsophalangeal (MTP1) joint, the other joints of the toes, the ankles and midfeet, and all tendons in the feet and ankles.

Results: DECT was measured at baseline in 187 of 211 patients. The mean (S.D.) serum urate level (μmol/l) decreased from 501 (80) at baseline to 311 (48) at 12 months, and 322 (67) at 24 months.DECT scores at all locations decreased during both the first and the second year (p< 0.001 for all comparisons vs baseline), both for patients achieving and not achieving the sUA treatment target.

Conclusions: In patients with gout, urate depositions in ankles and feet as measured by DECT decreased both in the first and the second year, when patients were treated using a treat-to-target ULT strategy.
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http://dx.doi.org/10.1093/rheumatology/keab533DOI Listing
July 2021

Associations Between Safety of Certolizumab Pegol, Disease Activity, and Patient Characteristics, Including Corticosteroid Use and Body Mass Index.

ACR Open Rheumatol 2021 Aug 1;3(8):501-511. Epub 2021 Jul 1.

Department of Medicine, Centre Hospitalier de l'Université de Montréal, Montréal, Quebéc, Canada.

Objective: To investigate the impact of baseline and time-varying factors on the risk of serious adverse events (SAEs) in patients during long-term certolizumab pegol (CZP) treatment.

Methods: Safety data were pooled across 34 CZP clinical trials in rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), and plaque psoriasis (PSO). Cox proportional hazards modeling was used to investigate the association of baseline patient characteristics with risk of serious infectious events (SIEs), malignancies, and major adverse cardiac events (MACEs). Cox modeling for recurrent events assessed the impact of time-varying body mass index (BMI), systemic corticosteroid (CS) use, and disease activity on SIE risk in RA and SAE risk in PSO.

Results: Data were pooled from 8747 CZP-treated patients across indications. Cox models reported a 44% increase in SIE risk associated with a baseline BMI of 35 kg/m or more versus a baseline BMI of 18.5 kg/m to less than 25 kg/m . Baseline systemic CS use, age of 65 years or more, and disease duration of 10 years or longer also increased SIE risk. Older age was the only identified risk factor for malignancies. The risk of MACEs increased 107% for BMI of 35 kg/m or more versus BMI of 18.5 kg/m to less than 25 kg/m and increased 51% for men versus women. Higher disease activity, older age, systemic CS use, BMI of 35 kg/m or more, and baseline comorbidities were SIE risk factors in RA. Age and systemic CS use were risk factors for SAEs in PSO.

Conclusion: Age, BMI, systemic CS use, and disease activity were identified as SIE risk factors in CZP-treated patients. Risk of malignancies was greater in older patients, whereas obesity and male sex were MACE risk factors.
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http://dx.doi.org/10.1002/acr2.11259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8363853PMC
August 2021

Rheumatoid factor and falsely elevated results in commercial immunoassays: data from an early arthritis cohort.

Rheumatol Int 2021 Sep 4;41(9):1657-1665. Epub 2021 May 4.

Department of Medical Biochemistry, Oslo University Hospital-Radiumhospitalet, Box 4953 Nydalen, 0424, Oslo, Norway.

The aim of the study was to  assess RF cross-reactivity to animal antibodies used in immunoassays, and to test if selected commercial immunoassays are vulnerable to interference from RF, causing false test results. Our study included samples from patients with RF-positive rheumatoid arthritis (RA) and controls (patients with RF-negative RA and psoriatic arthritis), included in an early arthritis-cohort. Reactivity to mouse IgG1, mouse IgG2a, rabbit IgG, bovine IgG, sheep/goat IgG and human IgG was analysed using in-house interference assays. RF-positive sera with strong reactivity to mouse IgG1 were analysed in three commercial immunoassays. To reveal interference, results before and after addition of blocking aggregated murine IgG1 were compared. Samples from 124 RF-positive RA patients and 66 controls were tested. We found considerably stronger reactivity toward animal antibodies, particularly mouse IgG1 (73% vs. 12%) and rabbit IgG (81% vs. 6%), in sera from RF-positive RA-patients compared to controls (p < 0.001). After selecting samples for testing in commercial assays, interference was revealed in 6/30 sera in the Architect β-hCG assay, 7/10 sera in the 27-plex cytokine assays, and in 2/33 samples in the Elecsys Soluble Transferrin Receptor assay. Our study revealed considerable RF reactivity to animal antibodies used in immunoassays and RF was associated with falsely elevated results in immunoassays used in clinical care and research. Clinicians, laboratorians, researchers and assay manufacturers must be alert to the risk of falsely elevated test results in RF-positive RA patients.
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http://dx.doi.org/10.1007/s00296-021-04865-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316178PMC
September 2021

Effect of Therapeutic Drug Monitoring vs Standard Therapy During Infliximab Induction on Disease Remission in Patients With Chronic Immune-Mediated Inflammatory Diseases: A Randomized Clinical Trial.

JAMA 2021 05;325(17):1744-1754

Division of Rheumatology and Research, Diakonhjemmet Hospital, Oslo, Norway.

Importance: Proactive therapeutic drug monitoring (TDM), defined as individualized drug dosing based on scheduled monitoring of serum drug levels, has been proposed as an alternative to standard therapy to maximize efficacy and safety of infliximab and other biological drugs. However, whether proactive TDM improves clinical outcomes when implemented at the time of drug initiation, compared with standard therapy, remains unclear.

Objective: To assess whether TDM during initiation of infliximab therapy improves treatment efficacy compared with standard infliximab therapy without TDM.

Design, Setting, And Participants: Randomized, parallel-group, open-label clinical trial of 411 adults with rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, ulcerative colitis, Crohn disease, or psoriasis initiating infliximab therapy in 21 hospitals in Norway. Patients were recruited from March 1, 2017, to January 10, 2019. Final follow-up occurred on November 5, 2019.

Interventions: Patients were randomized 1:1 to receive proactive TDM with dose and interval adjustments based on scheduled monitoring of serum drug levels and antidrug antibodies (TDM group; n = 207) or standard infliximab therapy without drug and antibody level monitoring (standard therapy group; n = 204).

Main Outcomes And Measures: The primary end point was clinical remission at week 30.

Results: Among 411 randomized patients (mean age, 44.7 [SD, 14.9] years; 209 women [51%]), 398 (198 in the TDM group and 200 in the standard therapy group) received their randomized intervention and were included in the full analysis set. Clinical remission at week 30 was achieved in 100 (50.5%) of 198 and 106 (53.0%) of 200 patients in the TDM and standard therapy groups, respectively (adjusted difference, 1.5%; 95% CI, -8.2% to 11.1%; P = .78). Adverse events were reported in 135 patients (68%) and 139 patients (70%) in the TDM and standard therapy groups, respectively.

Conclusions And Relevance: Among patients with immune-mediated inflammatory diseases initiating treatment with infliximab, proactive therapeutic drug monitoring, compared with standard therapy, did not significantly improve clinical remission rates over 30 weeks. These findings do not support routine use of therapeutic drug monitoring during infliximab induction for improving disease remission rates.

Trial Registration: ClinicalTrials.gov Identifier: NCT03074656.
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http://dx.doi.org/10.1001/jama.2021.4172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097498PMC
May 2021

Effect of Half-Dose vs Stable-Dose Conventional Synthetic Disease-Modifying Antirheumatic Drugs on Disease Flares in Patients With Rheumatoid Arthritis in Remission: The ARCTIC REWIND Randomized Clinical Trial.

JAMA 2021 05;325(17):1755-1764

Division of Rheumatology and Research, Diakonhjemmet Hospital, Oslo, Norway.

Importance: Sustained remission has become an achievable goal for patients with rheumatoid arthritis (RA) receiving conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), but how to best treat patients in clinical remission remains unclear.

Objective: To assess the effect of tapering of csDMARDs, compared with continuing csDMARDs without tapering, on the risk of flares in patients with RA in sustained remission.

Design, Setting, And Participants: ARCTIC REWIND was a multicenter, randomized, parallel, open-label noninferiority study conducted in 10 Norwegian hospital-based rheumatology practices. A total of 160 patients with RA in remission for 12 months who were receiving stable csDMARD therapy were enrolled between June 2013 and June 2018, and the final visit occurred in June 2019.

Interventions: Patients were randomly assigned to half-dose csDMARDs (n = 80) or stable-dose csDMARDs (n = 80).

Main Outcomes And Measures: The primary end point was the proportion of patients with a disease flare between baseline and the 12-month follow-up, defined as a combination of Disease Activity Score (DAS) greater than 1.6 (threshold for RA remission), an increase in DAS score of 0.6 units or more, and at least 2 swollen joints. A disease flare could also be recorded if both the patient and investigator agreed that a clinically significant flare had occurred. A risk difference of 20% was defined as the noninferiority margin.

Results: Of 160 enrolled patients (mean [SD] age, 55.1 [11.9] years; 66% female), 156 received the allocated therapy, of which 155 without any major protocol violations were included in the primary analysis population (77 receiving half-dose and 78 receiving stable-dose csDMARDs). Flare occurred in 19 patients (25%) in the half-dose csDMARD group compared with 5 (6%) in the stable-dose csDMARD group (risk difference, 18% [95% CI, 7%-29%]). Adverse events occurred in 34 patients (44%) in the half-dose group and 42 (54%) in the stable-dose group, none leading to study discontinuation. No deaths occurred.

Conclusions And Relevance: Among patients with RA in remission taking csDMARD therapy, treatment with half-dose vs stable-dose csDMARDs did not demonstrate noninferiority for the percentage of patients with disease flares over 12 months, and there were significantly fewer flares in the stable-dose group. These findings do not support treatment with half-dose therapy.

Trial Registration: ClinicalTrials.gov Identifier: NCT01881308.
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http://dx.doi.org/10.1001/jama.2021.4542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097499PMC
May 2021

Viral respiratory infections in patients treated with hydroxychloroquine.

Clin Exp Rheumatol 2021 Sep-Oct;39(5):1146. Epub 2021 Apr 7.

Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway.

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April 2021

12-month results from the real-life observational treat-to-target and tight-control therapy NOR-Gout study: achievements of the urate target levels and predictors of obtaining this target.

RMD Open 2021 03;7(1)

Rheumatology, Diakonhjemmet Hospital, Oslo, Norway.

Objectives: Gout is often not adequately treated, and we aimed to apply urate lowering treatment (ULT) combined with individual information to achieve target serum urate (sUA) in clinical practice, and to identify predictors of achievement of this sUA target.

Methods: Patients with a recent gout flare and sUA >360 µmol/L (>6 mg/dL) were consecutively included in a single-centre study and managed with a treat-to-target approach combining nurse-led information about gout with ULT. All patients were assessed with tight controls at baseline, 1, 2, 3, 6, 9 and 12 months including clinical examination, information on demographics, lifestyle, self-efficacy and beliefs about medicines. The treatment target was sUA <360 µmol/L and multivariable logistic regression was used to identify predictors of target attainment with ORs and 95% CIs.

Results: Of 211 patients (mean age 56.4 years, disease duration 7.8 years, 95% males), 186 completed the 12-month study. Mean sUA levels decreased from baseline mean 500 to 311 µmol/L at 12 months with 85.5% achieving the treatment target. Alcohol consumption at least weekly versus less frequently (OR 0.14; 95% CI 0.04 to 0.55) as well as beliefs in overuse of medicines (OR per unit 0.77; 95 CI 0.62 to 0.94) decreased the chance of reaching the treatment target, while higher self-efficacy for arthritis symptoms (OR 1.49 per 10 units; 95% CI 1.09 to 2.05) increased the likelihood.

Conclusions: This study shows that target sUA can be achieved with ULT in most patients. Less self-reported alcohol consumption, low beliefs in overuse of medicines and higher self-efficacy are associated with treatment success.
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http://dx.doi.org/10.1136/rmdopen-2021-001628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009238PMC
March 2021

Effectiveness of a Second Biologic After Failure of a Non-tumor Necrosis Factor Inhibitor As First Biologic in Rheumatoid Arthritis.

J Rheumatol 2021 Mar 1. Epub 2021 Mar 1.

This study was partly funded by grants from Nord-Forsk and FOREUM.
K. Chatzidionysiou, MD, PhD, Associate Professor, T. Frisell, PhD, Associate Professor, D. Di Giuseppe, PhD, K. Hellgren, MD, PhD, J. Askling, MD, PhD, Professor, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; M.L. Hetland, MD, PhD, Professor, B. Glintborg, MD, PhD, Associate Professor, DANBIO and Copenhagen Center for Arthritis Research (COPECARE), Center for Rheumatology and Spine Diseases, Centre of Head and Orthopedics, Rigshospitalet, and Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, on behalf of the DANBIO Registry, Copenhagen, Denmark; D. Nordström, MD, PhD, Professor, R. Peltomaa, MD, PhD, N. Trokovic, MS, Helsinki University and Hospital (ROB-FIN), Departments of Medicine and Rheumatology, Helsinki, Finland; K. Aaltonen, MD, PhD, Pharmaceuticals Pricing Board, Ministry of Social Affairs and Health, Helsinki, Finland; E.K. Kristianslund, MD, PhD, T.K. Kvien, MD, PhD, Professor, S.A. Provan, MD, PhD, Professor, Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway; B. Gudbjornsson, MD, PhD, Professor, Centre for Rheumatology Research, University Hospital, and Faculty of Medicine, University of Iceland, Reykjavik, Iceland; G. Grondal, MD, PhD, Professor, Department of Rheumatology and Centre for Rheumatology Research, University Hospital, Reykjavik, Iceland; L. Dreyer, MD, PhD, Professor, Department of Rheumatology, Aalborg University Hospital, and Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; L.E. Kristensen, MD, PhD, Professor, T.S. Jørgensen, MD, PhD, The Parker Institute, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Copenhagen, Denmark; L.T. Jacobsson, MD, PhD, Professor, Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. KC has received consultancy fees from Eli Lilly, AbbVie, and Pfizer. MLH has received grant/research support from BMS, MSD, AbbVie, Roche, Novartis, Biogen, and Pfizer; consultancy fees from Eli Lilly; and speaker's fees from Orion Pharma, Biogen, Pfizer, CellTrion, Merck, and Samsung Bioepis. DN has received consultancy fees from AbbVie, BMS, Celgene, MSD, Novartis, Pfizer, Roche, and UCB. BjG has received speaker fees from Novartis. TKK has received consulting fees, speaking fees, and/or honoraria from AbbVie, Amgen, Biogen, BMS, Celtrion, Egis, Eli Lilly, Evapharma, Ewopharma, Janssen, MSD, Mylan, Oktal Pharma, Orion Pharma, Pfizer, Roche, Sandoz, Sanofi, and UCB Pharma. LD has received grant/research support from BMS; consultancy fees from Janssen pharmaceuticals; and speaker's fees from Eli Lilly, UCB, and MSD. LEK has received consulting fees, speaking fees and/or honoraria from AbbVie, Amgen, Biogen, BMS, Eli Lilly, Janssen, Novartis, Pfizer, Sanofi, and UCB Pharma. TSJ has received consulting fees and/or speaking fees from AbbVie, Pfizer, Roche, Novartis, UCB, Biogen, and Eli Lilly. JA (as the principal investigator) and the Karolinska Institutet have entered into agreements with the following companies mainly regarding the safety monitoring of b/tsDMARDs in rheumatology: AbbVie, BMS, MSD, Eli Lilly, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB. The remaining authors declare no conflicts of interest relevant to this article. Address correspondence to Dr. K. Chatzidionysiou, Rheumatology Unit, Karolinska University Hospital, D2:00, 171 76, Solna, Stockholm, Sweden. Email: Accepted for publication February 19, 2021.

Objective: In rheumatoid arthritis (RA), evidence regarding the effectiveness of a second biologic disease- modifying antirheumatic drug (bDMARD) in patients whose first-ever bDMARD was a non-tumor necrosis factor inhibitor (TNFi) bDMARD is limited. The objective of this study was therefore to assess the outcome of a second bDMARD (non-TNFi: rituximab [RTX], abatacept [ABA], or tocilizumab [TCZ], separately; and TNFi) after failure of a non-TNFi bDMARD as first bDMARD.

Methods: We identified patients with RA from the 5 Nordic biologics registers who started treatment with a non-TNFi as first-ever bDMARD but switched to a second bDMARD. For the second bDMARD, we assessed drug survival (at 6 and 12 months) and primary response (at 6 months).

Results: We included 620 patients starting a second bDMARD (ABA 86, RTX 40, TCZ 67, and TNFi 427) following failure of a first non-TNFi bDMARD. At 6 and 12 months after start of their second bDMARD, approximately 70% and 60%, respectively, remained on treatment, and at 6 months, less than one-third of patients were still on their second bDMARD and had reached low disease activity or remission according to the Disease Activity Score in 28 joints. For those patients whose second bMDARD was a TNFi, the corresponding proportion was slightly higher (40%).

Conclusion: The drug survival and primary response of a second bDMARD in patients with RA switching due to failure of a non-TNFi bDMARD as first bDMARD is modest. Some patients may benefit from TNFi when used after failure of a non-TNFi as first bDMARD.
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http://dx.doi.org/10.3899/jrheum.201467DOI Listing
March 2021

Validity and reliability of the EULAR instrument RAID.7 as a tool to assess individual domains of impact of disease in rheumatoid arthritis: a cross-sectional study of 671 patients.

RMD Open 2021 02;7(1)

INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, INSERM, Sorbonne Université, Paris, France.

Objective: The rheumatoid arthritis impact of disease (RAID) questionnaire comprises seven patient-important domains of disease impact (pain, function, fatigue, sleep disturbance, emotional well-being, physical well-being, coping). RAID was validated as a pooled-weighted score. Its seven individual items separately could provide a valuable tool in clinical practice to guide interventions targeting the patient's experience of the disease. The aim was to separately assess the psychometric properties of each of the seven numeric rating scale (NRS) of the RAID (RAID.7).

Material And Methods: Post hoc analyses of data from the cross-sectional RAID study and from the Rainbow study, an open-label 12-week trial of etanercept in patients with RA. Construct validity of each NRS was assessed cross-sectionally in the RAID data set by Spearman's correlation with the respective external instrument of reference. Using the rainbow data set, we assessed reliability through intraclass correlation coefficient between the screening and the baseline visits and responsiveness (sensitivity to change) by standardised response mean between baseline and 12 weeks.

Results: A total of 671 patients with RA with features of established disease were analysed, 563 and 108 from RAID and Rainbow, respectively. The NRS correlated moderately to strongly with the respective external instrument of reference (r=0.62-0.81). Reliability ranged from 0.64 (0.51-0.74) (pain) to 0.83 (0.76-0.88) (sleep disturbance) and responsiveness from 0.93 (0.73-1.13) (sleep disturbance) to 1.34 (1.01-1.64) (pain).

Conclusion: The separate use of the individual NRS of RAID (RAID.7) is valid, feasible, reliable and sensitive to change, representing an opportunity to improve the assessment and treatment of disease impact with minimal questionnaire burden.

Trial Registration Number: NCT00768053.
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http://dx.doi.org/10.1136/rmdopen-2020-001539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871340PMC
February 2021

Value of MRI and ultrasound for prediction of therapeutic response and erosive progression in patients with early rheumatoid arthritis managed by an aggressive treat-to-target strategy.

RMD Open 2021 02;7(1)

Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway.

Objectives: To investigate if inflammation detected by MRI or ultrasound at rheumatoid arthritis (RA) onset is predictive of erosive progression or poor response to methotrexate monotherapy, and to investigate if subclinical inflammation in remission is predictive of future treatment escalation or erosive progression.

Methods: In a 2-year study, 218 patients with disease-modifying antirheumatic drug-naïve early RA were treated by a tight-control treat-to-target strategy corresponding to current recommendations. MRI and ultrasound were performed at regular intervals. Baseline imaging-based inflammation measures were analysed as predictors for early methotrexate failure and erosive progression using univariate and multivariate regression adjusted for clinical, laboratory and radiographic measures. In patients in remission after 1 year, imaging measures were analysed as predictors of treatment escalation and erosive progression during the second year. The added value of imaging in prediction models was assessed using receiver operating characteristic analyses.

Results: Baseline MRI inflammation was associated with MRI erosive progression and ultrasound with radiographic erosive progression. No imaging inflammation measure was associated with early methotrexate failure. Imaging inflammation was present in a majority of patients in clinical remission. Tenosynovitis was associated with treatment escalation, and synovitis and tenosynovitis with MRI/radiographic erosive progression during the second year. Imaging information did not improve prediction models for any of the outcomes.

Conclusions: Imaging-detected inflammation, both at diagnosis and in remission, is associated with elements of future disease development. However, the lack of a significant effect on prediction models indicates limited value of systematic MRI and ultrasound in management of early RA.
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http://dx.doi.org/10.1136/rmdopen-2020-001525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871342PMC
February 2021

Real-world 6 and 12-month Drug Retention, Remission and Response Rates of Secukinumab in 2,017 Psoriatic Arthritis patients in 13 European Countries.

Arthritis Care Res (Hoboken) 2021 Jan 18. Epub 2021 Jan 18.

Amsterdam University Medical Centres, location VU University medical centre, Department Rheumatology & Immunology Center (ARC), Amsterdam, the Netherlands.

Objective: There is a lack of real-life studies on IL-17 inhibition in psoriatic arthritis (PsA). We assessed real-life 6-/12-month effectiveness (i.e. retention, remission, low-disease-activity [LDA] and response rates) of the IL-17 inhibitor secukinumab in PsA patients overall, and across 1) number of prior biologic/targeted synthetic Disease-Modifying Anti-Rheumatic Drugs (b/tsDMARDs), 2) years since diagnosis, and 3) European registries.

Methods: Thirteen quality registries in rheumatology participating in the European Spondyloarthritis Research Collaboration Network provided longitudinal, observational data collected as part of routine care, for secondary use. Data were pooled and analysed with Kaplan-Meier plots, log-rank tests, Cox regression, and multiple linear and logistic regression analyses.

Results: A total of 2,017 PsA patients started treatment with secukinumab between 2015 and 2018. Overall secukinumab retention rates were 86%/76% after 6/12 months. Crude (LUNDEX adjusted) 6-month remission/LDA (LDA including remission) rates for DAPSA28, DAS28-CRP and SDAI were 13%/46% (11%/39%), 36%/55% (30%/46%) and 13%/56% (11%/47%), and 12-month rates 11%/46% (7%/31%), 39%/56% (26%/38%) and 16%/62% (10%/41%), respectively. CDAI remission/LDA rates were similar to the SDAI rates. Six-month ACR20/50/70 responses were 34%/19%/11% (29%/16%/9%); 12-month: 37%/21%/11% (24%/14%/7%). Secukinumab effectiveness was significantly better for b/tsDMARD naïve patients, similar across time since diagnosis (<2/2-4/>4 years) and varied significantly across the European registries.

Conclusion: In this large real-world study on secukinumab treatment in PsA, 6- and 12-month effectiveness was comparable to previous observational studies of TNFi. Retention, remission, LDA and response rates were significantly better for b/tsDMARD naïve patients, independent of time since diagnosis and varied significantly across the European countries.
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http://dx.doi.org/10.1002/acr.24560DOI Listing
January 2021

Secukinumab Provides Sustained Reduction in Fatigue in Patients with Ankylosing Spondylitis: Long-term Results of Two Phase III Randomized Controlled Trials.

Arthritis Care Res (Hoboken) 2020 Nov 23. Epub 2020 Nov 23.

Oregon Health & Science University, Portland, OR, United States.

Objective: To investigate the longer-term effects of secukinumab 150 mg on fatigue in patients with ankylosing spondylitis (AS) in MEASURE 1 (up to 3 years) and MEASURE 2 (up to 2 years).

Methods: Patients with active AS were randomized to secukinumab or placebo in MEASURE 1 (10 mg/kg intravenous [IV] followed by 150 mg subcutaneous [SC]) and MEASURE 2 (150 mg SC). Patients were naive to or had an inadequate response/intolerance to tumor necrosis factor inhibitors (anti-TNF-naive/ anti-TNF-IR). Fatigue was measured using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale. Relationships between fatigue response and baseline characteristics and clinical/laboratory variables were explored.

Results: Significant improvements in FACIT-F scores from baseline were observed with secukinumab across both studies versus placebo at week 16 (P < 0.05). Improvements were sustained through week 156 (MEASURE 1)/week 104 (MEASURE 2). Significantly more patients reported fatigue responses (FACIT-F increase ≥4; observed data) with secukinumab 150 mg than placebo at week 16 in both MEASURE 1 (P < 0.05) and MEASURE 2 (P < 0.01). Fatigue responses were achieved by 75.6% of patients receiving secukinumab at week 156 (MEASURE 1) and 81.4% at week 104 (MEASURE 2); these results were consistent in both anti-TNF-naive (74.3% and 84.6%) and anti-TNF-IR (81.3% and 75.0%) patients. Baseline characteristics did not predict improvement in fatigue consistently. Fatigue responses were moderately to strongly correlated with responses in several clinical measures, including Assessment of SpondyloArthritis international Society (ASAS)20/40, ASAS5/6 responses, Ankylosing Spondylitis Disease Activity Score-C reactive protein (ASDAS-CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Short-form (SF)-36 scores.

Conclusion: Secukinumab provided rapid and sustained improvements in fatigue for up to 3 years, regardless of prior anti-TNF exposure.
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http://dx.doi.org/10.1002/acr.24517DOI Listing
November 2020

What Next after Biologic Therapy Fails in Rheumatoid Arthritis?

N Engl J Med 2020 10;383(16):1588-1589

From the Department of Rheumatology, Diakonhjemmet Hospital (G.L.G., T.K.K.), and the Faculty of Medicine, University of Oslo (T.K.K.) - both in Oslo.

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http://dx.doi.org/10.1056/NEJMe2026142DOI Listing
October 2020

Drug retention, inactive disease and response rates in 1860 patients with axial spondyloarthritis initiating secukinumab treatment: routine care data from 13 registries in the EuroSpA collaboration.

RMD Open 2020 09;6(3)

Copenhagen Center for Arthritis Research (COPECARE), Center for Rheumatology and Spine Diseases, Centre for Head and Orthopedics, Rigshospitalet Glostrup, Copenhagen, Denmark.

Objectives: To explore 6-month and 12-month secukinumab effectiveness in patients with axial spondyloarthritis (axSpA) overall, as well as across (1) number of previous biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs), (2) time since diagnosis and (3) different European registries.

Methods: Real-life data from 13 European registries participating in the European Spondyloarthritis Research Collaboration Network were pooled. Kaplan-Meier with log-rank test, Cox regression, χ² and logistic regression analyses were performed to assess 6-month and 12-month secukinumab retention, inactive disease/low-disease-activity states (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) <2/<4, Ankylosing Spondylitis Disease Activity Score (ASDAS) <1.3/<2.1) and response rates (BASDAI50, Assessment of Spondyloarthritis International Society (ASAS) 20/40, ASDAS clinically important improvement (ASDAS-CII) and ASDAS major improvement (ASDAS-MI)).

Results: We included 1860 patients initiating secukinumab as part of routine care. Overall 6-month/12-month secukinumab retention rates were 82%/72%, with significant (p<0.001) differences between the registries (6-month: 70-93%, 12-month: 53-86%) and across number of previous b/tsDMARDs (b/tsDMARD-naïve: 90%/73%, 1 prior b/tsDMARD: 83%/73%, ≥2 prior b/tsDMARDs: 78%/66%). Overall 6-month/12-month BASDAI<4 were observed in 51%/51%, ASDAS<1.3 in 9%/11%, BASDAI50 in 53%/47%, ASAS40 in 28%/22%, ASDAS-CII in 49%/46% and ASDAS-MI in 25%/26% of the patients. All rates differed significantly across number of previous b/tsDMARDs, were numerically higher for b/tsDMARD-naïve patients and varied significantly across registries. Overall, time since diagnosis was not associated with secukinumab effectiveness.

Conclusions: In this study of 1860 patients from 13 European countries, we present the first comprehensive real-life data on effectiveness of secukinumab in patients with axSpA. Overall, secukinumab retention rates after 6 and 12 months of treatment were high. Secukinumab effectiveness was consistently better for bionaïve patients, independent of time since diagnosis and differed across the European countries.
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http://dx.doi.org/10.1136/rmdopen-2020-001280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539854PMC
September 2020

The impact of seropositivity on the effectiveness of biologic anti-rheumatic agents: results from a collaboration of 16 registries.

Rheumatology (Oxford) 2021 02;60(2):820-828

Rheumatology, University Hospitals of Geneva, Geneva, Switzerland.

Objectives: RF and ACPA are used as diagnostic tools and their presence has been associated with clinical response to some biologic DMARDs (bDMARDs) in RA. This study compared the impact of seropositivity on drug discontinuation and effectiveness of bDMARDs in patients with RA, using head-to-head comparisons in a real-world setting.

Methods: We conducted a pooled analysis of 16 observational RA registries. Inclusion criteria were a diagnosis of RA, initiation of treatment with rituximab (RTX), abatacept (ABA), tocilizumab (TCZ) or TNF inhibitors (TNFis) and available information on RF and/or ACPA status. Drug discontinuation was analysed using Cox regression, including drug, seropositivity, their interaction, adjusting for concomitant and past treatments and patient and disease characteristics and accounting for country and calendar year of bDMARD initiation. Effectiveness was analysed using the Clinical Disease Activity Index evolution over time.

Results: Among the 27 583 eligible patients, the association of seropositivity with drug discontinuation differed across bDMARDs (P for interaction <0.001). The adjusted hazard ratios for seropositive compared with seronegative patients were 1.01 (95% CI 0.95, 1.07) for TNFis, 0.89 (0.78, 1.02)] for TCZ, 0.80 (0.72, 0.88) for ABA and 0.70 (0.59, 0.84) for RTX. Adjusted differences in remission and low disease activity rates between seropositive and seronegative patients followed the same pattern, with no difference in TNFis, a small difference in TCZ, a larger difference in ABA and the largest difference in RTX (Lundex remission difference +5.9%, low disease activity difference +11.6%).

Conclusion: Seropositivity was associated with increased effectiveness of non-TNFi bDMARDs, especially RTX and ABA, but not TNFis.
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http://dx.doi.org/10.1093/rheumatology/keaa393DOI Listing
February 2021

Get a Grip on Factors Related to Grip Strength in Persons With Hand Osteoarthritis: Results From an Observational Cohort Study.

Arthritis Care Res (Hoboken) 2021 06;73(6):794-800

Diakonhjemmet Hospital and University of Oslo, Oslo, Norway.

Objective: To compare levels of grip strength in individuals with hand osteoarthritis (OA) with normative values, and to examine how hand OA severity and other biopsychosocial factors are associated with grip strength.

Methods: Levels of grip strength across age groups were compared with normative values from the general population in sex-stratified analyses using 2-sample t-tests. Associations between radiographic hand OA severity (Kellgren/Lawrence sum score) in different joint groups and grip strength of the same hand were examined in 300 individuals from the Nor-Hand study using linear regression. Analyses were repeated using markers of pain, demographic factors, comorbidities, and psychological and social factors as independent variables. We adjusted for age, sex, and body mass index.

Results: Individuals with hand OA had lower grip strength than the general population, especially in individuals age <60 years. In thumb base joints, increasing radiographic severity (range 0-8) and the presence of pain were associated with lower grip strength (β = -0.83 [95% confidence interval (95% CI) -1.12, -0.53] and β = -2.15 [95% CI -3.15, -1.16], respectively). Negative associations with grip strength were also found for women, low education, higher comorbidity index, and higher resting heart rate.

Conclusion: Individuals with hand OA have lower grip strength than the general population. Our results support the idea that studies on thumb base OA should include grip strength as an outcome measure. However, other biopsychosocial factors should also be considered when the grip strength is being interpreted, because other factors such as sex, socioeconomic factors, physical fitness, and comorbidities are negatively associated with grip strength.
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http://dx.doi.org/10.1002/acr.24385DOI Listing
June 2021

Considerations for improving quality of care of patients with rheumatoid arthritis and associated comorbidities.

RMD Open 2020 07;6(2)

Hôpital Cochin, Rheumatology, Université Paris Descartes, Paris, France.

Objective: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder with a global prevalence of approximately 0.5-1%. Patients with RA are at an increased risk of developing comorbidities (eg, cardiovascular disease, pulmonary disease, diabetes and depression). Despite this, there are limited recommendations for the management and implementation of associated comorbidities. This study aimed to identify good practice interventions in the care of RA and associated comorbidities.

Methods: A combination of primary research (180+ interviews with specialists across 12 European rheumatology centres) and secondary research (literature review of existing publications and guidelines/recommendations) were used to identify challenges in management and corresponding good practice interventions. Findings were prioritised and reviewed by a group of 18 rheumatology experts including rheumatologists, comorbidity experts, a patient representative and a highly specialised nurse.

Results: Challenges throughout the patient pathway (including delays in diagnosis and referral, shortage of rheumatologists, limited awareness of primary care professionals) and 18 good practice interventions were identified in the study. The expert group segmented and prioritised interventions according to three distinct stages of the disease: (1) suspected RA, (2) recent diagnosis of RA and (3) established RA. Examples of good practice interventions included enabling self-management (self-monitoring and disease management support, for example, lifestyle adaptations); early arthritis clinic; rapid access to care (online referral, triage, ultrasound-guided diagnosis); dedicated comorbidity specialists; enhanced communication with primary care (hotline, education sessions); and integrating patient registries into daily clinical practice.

Conclusion: Learning from implementation of good practice interventions in centres across Europe provides an opportunity to more widely improved care for patients with RA and associated comorbidities.
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http://dx.doi.org/10.1136/rmdopen-2020-001211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722279PMC
July 2020

Ultrasound shows rapid reduction of crystal depositions during a treat-to-target approach in gout patients: 12-month results from the NOR-Gout study.

Ann Rheum Dis 2020 11 15;79(11):1500-1505. Epub 2020 Jul 15.

Department of Rheumatology, Diakonhjemmet Sykehus, Oslo, Norway.

Objectives: As ultrasound is sensitive for detecting crystal depositions in patients with gout, our objectives were to explore the main locations for depositions and the extent of dissolution of depositions during a treat-to-target approach with urate lowering treatment (ULT) in patients with gout.

Methods: Patients with a recent flare of gout were consecutively included in this single-centre study and managed by a treat-to-target approach with ULT. All patients were assessed at baseline, 3, 6 and 12 months including bilateral ultrasound examinations of joints/tendons/entheses of hands, elbows, knees, ankles and feet. A new semiquantitative scoring system of 0-3 of elementary lesions (double contour (DC), tophi and aggregates) was applied to quantify the amount of depositions during the follow-up.

Results: 209 of the patients were evaluated with ultrasound at baseline (mean (SD) age 56.4 (13.8) years and disease duration 7.9 (7.7) years, 95.2% men). The serum urate levels decreased from baseline to 12 months (mean (SD) 500 (77) to 312 (49) µmol/L) (p<0.001)). The first metatarsophalangeal joint was the most frequent location for all the elementary lesions and erosions were associated with higher levels of crystal depositions. From baseline to 12 months, mean sum scores decreased for DC (4.3 to 1.3), tophi (6.5 to 3.8) and aggregates (9.3 to 6.7) (p<0.001 for all), with DC being most sensitive to change.

Conclusions: The ultrasound scoring system for crystal depositions was sensitive to change and showed that a treat-to-target approach with ULT resulted in significant reductions of all the depositions, most extensively for DC.
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http://dx.doi.org/10.1136/annrheumdis-2020-217392DOI Listing
November 2020

Does Older Age have an Impact on Rituximab Efficacy and Safety? Results from the NOR-DMARD Register.

Drugs Aging 2020 08;37(8):617-626

Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway.

Objective: The objective of this study was to compare the efficacy and safety of rituximab in older vs younger patients with rheumatoid arthritis.

Methods: Data on 367 patients with rheumatoid arthritis treated with rituximab in the Norwegian Disease-Modifying Antirheumatic Drug (NOR-DMARD) register were analysed, comparing patients aged ≥ 65 years (n = 91) with patients aged < 65 years (n = 276). Drug survival was compared using a Kaplan-Meier analysis and Cox proportional hazard models. Disease activity, as assessed by the Disease Activity Score based on 28 joints and erythrocyte sedimentation rate (DAS28-ESR) and the Simplified Disease Activity Index, was analysed with linear mixed models. The occurrence of adverse events was analysed by quasi-Poisson regression models.

Results: Drug survival was similar in the two age groups. The proportion of patients who remained taking rituximab over 2 years was 72% in those under aged 65 years vs 74% in those aged ≥ 65 years. No statistically significant association with age was found for drug survival in either the unadjusted (hazard ratio 1.13, p = 0.65) or adjusted Cox proportional hazard analyses for the model with DAS28-ESR as a confounder (effect size 1.11, p = 0.73). Models including the Simplified Disease Activity Index instead of DAS28-ESR yielded similar results. Age was furthermore not significantly associated with disease activity over time, although there was a tendency towards a poorer response in older patients. In the older age group, there was a higher incidence of pneumonia (107 vs 51 per 1000 patient-years) and other serious infections (142 vs 66 per 1000 patient-years).

Conclusions: Rituximab is a reasonable therapeutic option for older patients with rheumatoid arthritis although vigilance is needed with regard to the infection profile.

Trial Registration: ClinicalTrials.gov Identifier: NCT01581294.
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http://dx.doi.org/10.1007/s40266-020-00782-xDOI Listing
August 2020

Inflammatory hallmarks of lesser prominence in psoriatic arthritis patients starting biologics: a Nordic population-based cohort study.

Rheumatology (Oxford) 2021 01;60(1):140-146

Parker Institute, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Copenhagen.

Objectives: To assess secular trends in baseline characteristics of PsA patients initiating their first or subsequent biologic DMARD (bDMARD) therapy and to explore prescription patterns and treatment rates of bDMARDs from 2006 to 2017 in the Nordic countries.

Methods: PsA patients registered in the Nordic rheumatology registries initiating any treatment with bDMARDs were identified. The bDMARDs were grouped as original TNF inhibitor [TNFi; adalimumab (ADA), etanercept (ETN) and infliximab (IFX)]; certolizumab pegol (CZP) and golimumab (GOL); biosimilars and ustekinumab, based on the date of release. Baseline characteristics were compared for the five countries, supplemented by secular trends with R2 calculations and point prevalence of bDMARD treatment.

Results: A total of 18 089 patients were identified (Denmark, 4361; Iceland, 449; Norway, 1948; Finland, 1069; Sweden, 10 262). A total of 54% of the patients were female, 34.3% of patients initiated an original TNFi, 8% CZP and GOL, 7.5% biosimilars and 0.3% ustekinumab as a first-line bDMARD. Subsequent bDMARDs were 25.2% original TNFi, 9% CZP and GOL, 12% biosimilars and 2.1% ustekinumab. From 2015 through 2017 there was a rapid uptake of biosimilars. The total of first-line bDMARD initiators with lower disease activity increased from 2006 to 2017, where an R2 close to 1 showed a strong association.

Conclusion: Across the Nordic countries, the number of prescribed bDMARDs increased from 2006 to 2017, indicating a previously unmet need for bDMARDs in the PsA population. In recent years, PsA patients have initiated bDMARDs with lower disease activity compared with previous years, suggesting that bDMARDs are initiated in patients with a less active inflammatory phenotype.
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http://dx.doi.org/10.1093/rheumatology/keaa237DOI Listing
January 2021

Rapid and sustained improvements in patient-reported signs and symptoms with ixekizumab in biologic-naive and TNF-inadequate responder patients with psoriatic arthritis.

Clin Exp Rheumatol 2021 Mar-Apr;39(2):329-336. Epub 2020 Jun 19.

Diakonhjemmet Hospital, Oslo, Norway.

Objectives: To analyse the onset and sustainability of patient-reported improvements in symptoms of psoriatic arthritis (PsA) following treatment with ixekizumab (IXE) up to Week 108.

Methods: In patients with active PsA, either naive to biological DMARDs (SPIRIT-P1) or having inadequate response or intolerance to 1 or 2 prior TNF-inhibitors (TNFi‑experienced; SPIRIT-P2), we analysed the change from baseline in joint pain visual analogue scale (VAS; 0-100 scale), patient global assessment (PatGA VAS; 0-100 scale), fatigue numerical rating scale (NRS; 0 [no fatigue] to 10 [worst imaginable]), and Health Assessment Questionnaire-Disability Index (HAQ-DI; 0-3), up to Week 108.

Results: IXE-treated patients compared to placebo reported rapid and statistically significant improvement in pain VAS, PatGA, and HAQ-DI as early as Week 1 and this benefit was sustained or increased through Week 108. Fatigue scores improved in IXE-treated patients compared to placebo in both studies; results were statistically significant at Week 24 only in SPIRIT-P2. Improvements in fatigue with IXE were sustained over 2 years. The improvements observed in these patient-reported outcomes (PROs) were consistent in biologic-naive or TNFi-experienced patients.

Conclusions: Patients treated with IXE versus PBO achieved significantly greater improvements and showed faster onset of improvements in patient-reported outcomes measuring symptoms and impact of PsA. Responses were sustained over 2 years and were generally consistent regardless of prior TNFi experience.
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April 2021

Development and validation of an alternative ankylosing spondylitis disease activity score when patient global assessment is unavailable.

Rheumatology (Oxford) 2021 02;60(2):638-648

Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.

Objective: To develop an alternative Ankylosing Spondylitis Disease Activity Score (ASDAS) to be used in research settings in axial SpA (axSpA) when Patient Global Assessment (PGA) is unavailable in databases.

Methods: Longitudinal data from four axSpA cohorts and two randomized controlled trials were combined. Observations were randomly split in a development (N = 1026) and a validation cohort (N = 1059). Substitutes of PGA by BASDAI total score, single or combined individual BASDAI questions, and a constant value, were established in the development cohort. Conversion factors for each substitute were defined by Generalized Estimating Equations, obtaining seven 'alternative' formulae. Validation was performed in the validation cohort according to the OMERACT filter, taking into consideration: (i) truth (agreement with original-ASDAS in the continuous score, by intraclass correlation coefficient and in disease activity states, by weighted kappa); (ii) discrimination [standardized mean difference of ASDAS scores between high/low disease activity states defined by external anchors, e.g. Patient Acceptable Symptom State; agreement (kappa) in the percentage of patients reaching ASDAS improvement criteria according to alternative vs original formulae]; and (iii) feasibility.

Results: Comparing various options, alternative-ASDAS using BASDAI total as PGA replacement proved to be: truthful (intraclass correlation coefficient = 0.98, kappa = 0.90), discriminative [ASDAS scores between Patient Acceptable Symptom State no/yes: standardized mean difference = 1.37 (original-ASDAS standardized mean difference = 1.43); agreement with original-ASDAS in major improvement/clinically important improvement criteria: kappa = 0.93/0.88] and feasible (BASDAI total often available, as questions required for the ASDAS; conversion coefficient ≈ 1).

Conclusion: Alternative-ASDAS using BASDAI total score as PGA replacement is the most truthful, discriminative and feasible instrument.
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http://dx.doi.org/10.1093/rheumatology/keaa241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850538PMC
February 2021

Comparison of remission and low disease activity states with DAPSA, MDA and VLDA in a clinical trial setting in psoriatic arthritis patients: 2-year results from the FUTURE 2 study.

Semin Arthritis Rheum 2020 08 15;50(4):709-718. Epub 2020 May 15.

Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria.

Objectives: Remission (REM) or low disease activity (LDA) states were compared in a clinical trial setting of the FUTURE 2 study (NCT01752634) using Disease Activity Index for Psoriatic Arthritis (DAPSA) and Minimal Disease Activity (MDA) composite indices in secukinumab treated PsA patients.

Methods: The proportion of patients reaching DAPSA-REM (cut-off ≤4) or REM+LDA (≤14), and very low disease activity (VLDA; achieving 7/7 criteria) or MDA (≥5/7), were compared in the overall population, by prior use of anti-TNF therapy, and by time since diagnosis using as observed data. The proportion of patients who met individual core component and other variables of interest were also computed to assess residual disease activity in DAPSA-REM/REM+LDA states and VLDA/MDA responses. The relationship between DAPSA/MDA and patient reported outcomes (PROs), including health-related quality of life, physical function, and fatigue were assessed using mixed model for repeated measures.

Results: More patients could achieve DAPSA-REM or DAPSA-REM+LDA status than VLDA or MDA responses, respectively, at all the time points in the overall population, irrespective of anti‒TNF status and time since diagnosis. Higher proportion of patients reaching DAPSA-REM or VLDA achieved more thresholds of core components (joints, pain, patient and physician global assessments, and function) than DAPSA-REM+LDA or MDA over Week 104. There were differences with numerically higher proportion of patients achieving patient global assessment ≤10 mm and ≤20 mm, and physician global assessment ≤10 mm with MDA than with DAPSA-REM+LDA, and patient pain VAS ≤15 mm, PASI ≤1, HAQ ≤0.5 with VLDA or MDA than with DAPSA-REM or DAPSA-REM+LDA, respectively, through 104 weeks. Improvements in PROs were significantly better for patients in DAPSA-REM+LDA versus DAPSA-moderate+high disease activity status, and for MDA responders versus non-responders.

Conclusion: These analysis add to the evidence that both DAPSA and MDA composite index measures can be used for evaluation of the status and treatment response utilizing a treat to target approach in PsA patients in a clinical trial setting and improve patient health related outcomes.

Funding: The study and analysis was funded by Novartis Pharma AG, Basel, Switzerland.
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http://dx.doi.org/10.1016/j.semarthrit.2020.03.015DOI Listing
August 2020

EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2019 update.

Ann Rheum Dis 2020 06;79(6):700-712

Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Wien, Austria.

Objective: To update the European League Against Rheumatism (EULAR) recommendations for the pharmacological treatment of psoriatic arthritis (PsA).

Methods: According to the EULAR standardised operating procedures, a systematic literature review was followed by a consensus meeting to develop this update involving 28 international taskforce members in May 2019. Levels of evidence and strengths of recommendations were determined.

Results: The updated recommendations comprise 6 overarching principles and 12 recommendations. The overarching principles address the nature of PsA and diversity of both musculoskeletal and non-musculoskeletal manifestations; the need for collaborative management and shared decision-making is highlighted. The recommendations provide a treatment strategy for pharmacological therapies. Non-steroidal anti-inflammatory drugs and local glucocorticoid injections are proposed as initial therapy; for patients with arthritis and poor prognostic factors, such as polyarthritis or monoarthritis/oligoarthritis accompanied by factors such as dactylitis or joint damage, rapid initiation of conventional synthetic disease-modifying antirheumatic drugs is recommended. If the treatment target is not achieved with this strategy, a biological disease-modifying antirheumatic drugs (bDMARDs) targeting tumour necrosis factor (TNF), interleukin (IL)-17A or IL-12/23 should be initiated, taking into account skin involvement if relevant. If axial disease predominates, a TNF inhibitor or IL-17A inhibitor should be started as first-line disease-modifying antirheumatic drug. Use of Janus kinase inhibitors is addressed primarily after bDMARD failure. Phosphodiesterase-4 inhibition is proposed for patients in whom these other drugs are inappropriate, generally in the context of mild disease. Drug switches and tapering in sustained remission are addressed.

Conclusion: These recommendations provide stakeholders with an updated consensus on the pharmacological management of PsA, based on a combination of evidence and expert opinion.
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http://dx.doi.org/10.1136/annrheumdis-2020-217159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286048PMC
June 2020

The Patient Experienced Symptom State (PESS): a patient-reported global outcome measure that may better reflect disease remission status.

Rheumatology (Oxford) 2020 Nov;59(11):3458-3467

Faculty of Health and Welfare, Østfold University College, Halden.

Objectives: In RA, Patient Acceptable Symptom State assesses disease from the patient's perspective, which does not correspond either to disease remission or to full control of disease impact. This study aims to explore the properties of a novel multilevel Patient Experienced Symptom State (PESS).

Methods: This was a cross-sectional analysis of two datasets of patients with RA. PESS was assessed through the question: 'Consider how your RA has affected you. If you remain in the coming months as you have been the last week, how would you rate your condition?', with five levels (from 'very bad' to 'very good'). Construct validity of PESS was assessed against validated disease activity [DAS28, Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI)] and impact measures [RA Impact of Disease (RAID) and modified HAQ]. Multiple pairwise comparisons between groups and receiver-operating characteristic curves with Youden Index were performed.

Results: A total of 1407 patients [74% female, mean (S.d.) age 53.5 (13.4) years, mean disease duration 14.3 (12.0) years and mean DAS28 3.0 (1.5)] were analysed. Overall, 16.3% considered themselves as being in 'very good', 21.6% in 'good' and 31.9% in 'acceptable' state. Disease activity and impact measures differed significantly across the five levels (P < 0.01). Cut-off values corresponding to 'good' and 'very good' PESS states were in the range of low disease activity/remission (for 'good' and 'very good': DAS28-ESR-4v ≤2.6/≤2.3; CDAI ≤5.0/≤3.1; SDAI ≤5.1/≤3.8, respectively) and very low disease impact (RAID domains all ≤1).

Conclusion: PESS 'very good' status corresponds to currently recommended targets for RA management and reflects full control of disease impact. PESS appears to be an easy-to-use and relevant measure in the evaluation of patients with RA.
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http://dx.doi.org/10.1093/rheumatology/keaa149DOI Listing
November 2020

Prediction of cardiovascular events in rheumatoid arthritis using risk age calculations: evaluation of concordance across risk age models.

Arthritis Res Ther 2020 04 23;22(1):90. Epub 2020 Apr 23.

Preventive Cardio-Rheuma clinic, Department of Rheumatology, Diakonhjemmet Hospital, PO Box 23, Vindern, N-01319, Oslo, Norway.

Background: In younger individuals, low absolute risk of cardiovascular disease (CVD) may conceal an increased risk age and relative risk of CVD. Calculation of risk age is proposed as an adjuvant to absolute CVD risk estimation in European guidelines. We aimed to compare the discriminative ability of available risk age models in prediction of CVD in rheumatoid arthritis (RA). Secondly, we also evaluated the performance of risk age models in subgroups based on RA disease characteristics.

Methods: RA patients aged 30-70 years were included from an international consortium named A Trans-Atlantic Cardiovascular Consortium for Rheumatoid Arthritis (ATACC-RA). Prior CVD and diabetes mellitus were exclusion criteria. The discriminatory ability of specific risk age models was evaluated using c-statistics and their standard errors after calculating time until fatal or non-fatal CVD or last follow-up.

Results: A total of 1974 patients were included in the main analyses, and 144 events were observed during follow-up, the median follow-up being 5.0 years. The risk age models gave highly correlated results, demonstrating R values ranging from 0.87 to 0.97. However, risk age estimations differed > 5 years in 15-32% of patients. C-statistics ranged 0.68-0.72 with standard errors of approximately 0.03. Despite certain RA characteristics being associated with low c-indices, standard errors were high. Restricting analysis to European RA patients yielded similar results.

Conclusions: The cardiovascular risk age and vascular age models have comparable performance in predicting CVD in RA patients. The influence of RA disease characteristics on the predictive ability of these prediction models remains inconclusive.
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http://dx.doi.org/10.1186/s13075-020-02178-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178602PMC
April 2020
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