Extended ultrasound examination identifies more large vessel involvement in patients with giant cell arteritis.

OBJECTIVES: To compare limited with a more extended ultrasound examination (anteromedial ultrasound, A2-ultrasound) to detect large vessel (LV) involvement in patients with newly diagnosed GCA. METHODS: Patients with new-onset GCA were included at the time of diagnosis. All patients were examined using limited ultrasound (ultrasound of the axillary artery as visualized in the axilla) and an extended A2-ultrasound method (which also includes the carotid, vertebral, subclavian and proximal axillary arteries), in addition to temporal artery ultrasound. RESULTS: One hundred and thirty-three patients were included in the study. All patients fulfilled the criteria according to a proposed extension of the 1990 ACR classification criteria for GCA and had a positive ultrasound examination at diagnosis. Ninety-three of the 133 GCA patients (69.9%) had LV involvement when examined by extended A2-ultrasound, compared with only 56 patients (42.1%) by limited ultrasound (P < 0.001). Twelve patients (9.0%) had vasculitis of the vertebral arteries as the only LVs involved. Five patients (3.8%) would have been missed as having GCA if only limited ultrasound was performed. Forty patients (30.0%) had isolated cranial GCA, 21 patients (15.8%) had isolated large vessel GCA and 72 patients (54.1%) had mixed-GCA. CONCLUSION: Extended A2-ultrasound examination identified more patients with LV involvement than the limited ultrasound method. However, extended A2-ultrasound requires high expertise and high-end equipment and should be performed by ultrasonographers with adequate training.

Exploring the impact of the national tender system on the use of costly drugs treating rheumatoid arthritis patients in ten rheumatology centers in Norway (2010-2019).

BACKGROUND: Biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) are highly effective in treating rheumatoid arthritis (RA), albeit high drug cost has restricted their use in many countries. As a countermeasure, Norway implemented pharmaceutical tendering as a cost-reducing strategy. The aim of this study was to assess the annual proportion of different b/tsDMARDs registered to treat RA patients under the influence of a Norwegian pharmaceutical tendering between 2010 and 2019. METHOD: The data is collected from ten Norwegian outpatient centers. The included patients are categorized as naïve, non-naïve, and current b/tsDMARD users. 13 individual b/tsDMARDs are assessed and compared with the tender rankings from each year. Overview of subcutaneous (sc) with per oral vs. intravenous (iv) and biosimilars vs. non-biosimilar are also described. RESULT: The tender-winning b/tsDMARD was the most or second most used drug in nine out of ten years for naïve users, seven for non-naïve users, and twice for current users. The average sum of the highest and second highest proportion among naïve, non-naïve, and current b/tsDMARD users were 75%, 53%, and 50% during the ten years, respectively. The tender-winning drug was iv in eight out of ten years. However, the average total proportion of sc and per oral b/tsDMARDs was about 70% for naïve b/tsDMARD users, 50% for non-naïve b/tsDMARD users, and 60% for current b/tsDMARD users. The main contributors to sc and per oral b/tsDMARD were etanercept (reference and biosimilar) and certolizumab pegol. The main contributors to iv b/tsDMARD were rituximab reference and infliximab biosimilar. Despite low-ranking offers, rituximab reference (offered as a second-line drug) often achieved a high proportion among non-naïve and current b/tsDMARD users. After the introduction of biosimilars, their average proportion was about 40%, 40%, and 20% for naïve, non-naïve, and current b/tsDMARD users, respectively. CONCLUSION: Based on observed data, a higher tender rank was associated with a higher proportion among naïve and non-naïve b/tsDMARD users. However, in most cases, sc b/tsDMARDs achieved a higher proportion with lower tender ranks than iv b/tsDMARDs with higher tender ranks.

Exploring drug cost and disease outcome in rheumatoid arthritis patients treated with biologic and targeted synthetic DMARDs in Norway in 2010-2019 - a country with a national tender system for prescription of costly drugs.

BACKGROUND: In Norway, an annual tender system for the prescription of biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) has been used since 2007. This study aimed to explore annual b/tsDMARDs costs and disease outcomes in Norwegian rheumatoid arthritis (RA) patients between 2010 and 2019 under the influence of the tender system. METHODS: RA patients monitored in ordinary clinical practice were recruited from 10 Norwegian centers. Data files from each center for each year were collected to explore demographics, disease outcomes, and the prescribed treatment. The cost of b/tsDMARDs was calculated based on the drug price given in the annual tender process. RESULTS: The number of registered RA patients increased from 4909 in 2010 to 9335 in 2019. The percentage of patients receiving a b/tsDMARD was 39% in 2010 and 45% in 2019. The proportion of b/tsDMARDs treated patients achieving DAS28 remission increased from 42 to 67%. The estimated mean annual cost to treat a patient on b/tsDMARDs fell by 47%, from 13.1 thousand euros (EUR) in 2010 to 6.9 thousand EUR in 2019. The mean annual cost to treat b/tsDMARDs naïve patients was reduced by 75% (13.0 thousand EUR in 2010 and 3.2 thousand EUR in 2019). CONCLUSIONS: In the period 2010-2019, b/tsDMARD treatment costs for Norwegian RA patients were significantly reduced, whereas DAS28 remission rates increased. Our data may indicate that the health authorities' intention to reduce treatment costs by implementing a tender system has been successful.

Comparative Effectiveness and Persistence of SB4 and Reference Etanercept in Patients With Psoriatic Arthritis in Norway.

OBJECTIVE: We aim to compare drug effectiveness and persistence between the reference etanercept (ETN) and ETN biosimilar SB4 in patients with psoriatic arthritis (PsA) naive to ETN and to investigate drug effectiveness and persistence in those undergoing a mandatory nonmedical switch from ETN to SB4. METHODS: We used a retrospective comparative database study including 1,138 patients with PsA treated with ETN or SB4 (years 1999-2021) in Norway. Disease activity score in 28 joints (DAS28) and drug persistence were compared between unmatched ETN (n = 644) and SB4 (n = 252) cohorts and in matched analyses (n = 144, both cohorts) at baseline using a propensity score (PS) to adjust for confounders. Drug persistence was analyzed with the Kaplan-Meier method. RESULTS: In unmatched analyses, difference in change from baseline between ETN (n = 140) and SB4 (n = 132) for DAS28 at one year was mean 0.67 (95% confidence interval [CI] 0.38-0.96) in favor of ETN. In PS-matched analyses, the difference in change from baseline between ETN (n = 54) and SB4 (n = 54) was mean 0.09 (95% CI -0.33 to 0.50), and the mean difference assessed with an analysis of covariance model was 0.01 (95% CI -0.38 to 0.40), both within predefined equivalence margin (±0.6). Drug persistence at one year was mean 0.75 (95% CI 0.71-0.78) for ETN, mean 0.58 (95% CI 0.51-0.63) for SB4, hazard ratio (HR) 2.45 (95% CI 2.02-2.97) in unmatched analysis, and mean 0.55 (95% CI 0.46-0.63) for ETN, mean 0.60 (95% CI 0.51-0.67) for SB4, HR 1.29 (95%CI 0.94-1.76) in PS-matched cohorts. CONCLUSION: At one year, outcomes for PsA disease activity and drug persistence were comparable for patients treated with either ETN or SB4. In patients undergoing a mandatory nonmedical switch from ETN to SB4, drug effectiveness was maintained during a two-year period.

Factors predicting death and cancer in patients with giant cell arteritis in Western Norway 1972-2012: a retrospective observational cohort study.

Objectives: Evidence as to whether or not giant cell arteritis (GCA) confers added risk of cancer or death is conflicting. Our aim was to identify factors predicting death or cancer in a large Norwegian GCA-cohort. Methods: This is a retrospective observational cohort study including patients diagnosed with GCA in Western Norway during 1972-2012. Patients were identified through computerized hospital records using the International Classification of Diseases coding. Medical records were reviewed and data about registered deaths and cancer occurrences were extracted from the Norwegian Cause of Death Registry and the Cancer Registry of Norway. We investigated predicting factors using Cox proportional hazards regression. Results: We identified 881 cases with a validated diagnosis of GCA (60% biopsy-verified). 490 patients (56%) died during the study period. Among 767 patients with no registered cancer prior to GCA diagnosis, 120 (16%) were diagnosed with cancer during the study period. Traditional risk factors were the main predictors of death; age at time of GCA-diagnosis [hazard ratio (HR) 2.81], smoking (HR 1.61), hypertension (HR 1.48) and previous cardiovascular disease (HR 1.26). Hemoglobin (Hb) level was also associated with risk of death with increasing Hb-levels at time of GCA-diagnosis indicating decreased risk of death (HR 0.91). Other GCA-related factors were not predictive of death. We did not identify any predictors of cancer risk. Conclusion: In our cohort of GCA-patients, the risk of death was predominantly predicted by age and traditional risk factors. We found no significant associations with regards to the risk of incident cancer.

Norwegian society of rheumatology recommendations on diagnosis and treatment of patients with giant cell arteritis.

Objective: To provide clinical guidance to Norwegian Rheumatologists and other clinicians involved in diagnosing and treating patients with giant cell arteritis (GCA). Methods: The available evidence in the field was reviewed, and the GCA working group wrote draft guidelines. These guidelines were discussed and revised according to standard procedures within the Norwegian Society of Rheumatology. The European Alliance of Associations for Rheumatology (EULAR) recommendations for imaging and treatment in large vessel vasculitis and the British Society for Rheumatology (BSR) guidelines for diagnostics and treatment in GCA informed the development of the current guidelines. Results: A total of 13 recommendations were developed. Ultrasound is recommended as the primary diagnostic test. In patients with suspected GCA, treatment with high doses of Prednisolone (40-60 mg) should be initiated immediately. For patients with refractory disease or relapse, Methotrexate (MTX) should be used as the first-line adjunctive therapy, followed by tocilizumab (TCZ). Conclusion: Norwegian recommendations for diagnostics and treatment to improve management and outcome in patients with GCA were developed.

Risk of Cancer in 767 Patients with Giant Cell Arteritis in Western Norway: A Retrospective Cohort with Matched Controls.

OBJECTIVE: To determine the risk of cancer in a large Norwegian cohort of patients with giant cell arteritis (GCA). METHODS: This is a hospital-based, retrospective, observational cohort study including patients diagnosed with GCA in the Bergen Health Area during 1972-2012. Patients were identified through computerized hospital records using the International Classification of Diseases coding system. Medical records were reviewed. Each patient was randomly assigned population controls matched on age, sex, and geography from the Central Population Registry of Norway. Data on the occurrence of cancer were obtained from the Cancer Registry of Norway. The cumulative risk of malignancy was estimated using Kaplan-Meier methods and potential differences were analyzed using the Gehan-Breslow and log-rank tests. RESULTS: We identified 881 cases with a clinical diagnosis of GCA, of which 792 fulfilled the American College of Rheumatology (ACR) 1990 classification criteria and 528 were biopsy-verified. Cases with no registered cancer prior to GCA diagnosis were included in a time-to-event analysis, with first cancer as the event (n = 767 with clinical GCA diagnosis, 686 fulfilling ACR criteria for GCA, 463 biopsy-verified). These cases were matched with previously cancer-free population controls (n = 1437, 1284, 895, respectively). We found no significant difference in the risk of malignancy after time of diagnosis/matching for GCA patients compared to population controls (p > 0.05). CONCLUSION: In this study of a large and well-characterized cohort of patients with GCA, there was no difference in the risk of malignancy in patients with GCA compared to matched population controls.