Taper versus discontinuation of tocilizumab in patients with giant cell arteritis: Real-world experience from a tertiary center.

INTRODUCTION: Following the approval of tocilizumab (TCZ) for giant cell arteritis (GCA), recent studies have shown a high relapse frequency after abrupt discontinuation of TCZ. However, a thorough exploration of TCZ tapering compared to abrupt discontinuation has never been undertaken. Likewise, adverse events have only been scarcely investigated in routine care. This study aimed to compare the incidence of relapses in GCA patients undergoing TCZ tapering compared to abrupt discontinuation. METHODS: We performed a single-center retrospective cohort study from 2012 to 2022. Data from GCA patients treated with TCZ was obtained from the Electronic Patients Record. Relapse-free survival is reported in Kaplan-Meier plots and tapering versus abrupt discontinuation were compared using a Wilcoxon-Brewlos-Gehan test. RESULTS: We included 155 patients receiving TCZ treatment for GCA, of which 104 discontinued TCZ. Among the 104 patients discontinuing TCZ, 42 (40 %) experienced a relapse within the first year. A total of 57 patients underwent taper with 6/38 (16 %) and 2/19 (11 %) relapsing while receiving TCZ every second or third week, respectively. In comparison, 59 patients underwent abrupt discontinuation with 27 (46 %) relapsing during follow-up. The patients undergoing abrupt TCZ discontinuation demonstrated a significantly shorter time to relapse compared to all tapered patients (p = 0.02) as well as patients tapered from weekly TCZ treatment to every second week (p < 0.01). Furthermore, 15 % of patients discontinued TCZ due to adverse events. CONCLUSION: This is the first study indicating that TCZ taper induced longer relapse-free survival than abrupt discontinuation, implying that taper may be favored over discontinuation in patients with GCA.

The DANIsh VASculitis cohort study: protocol for a national multicenter prospective study including incident and prevalent patients with giant cell arteritis and polymyalgia rheumatica.

The DANIsh VASculitis cohort study, DANIVAS, is an observational national multicenter study with the overall aim to prospectively collect protocolized clinical data and biobank material from patients with polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) diagnosed and/or followed at Danish rheumatology departments. A long-term key objective is to investigate whether the use of new clinically implemented diagnostic imaging modalities facilitates disease stratification in the GCA-PMR disease spectrum. In particular, we aim to evaluate treatment requirements in GCA patients with and without large-vessel involvement, treatment needs in PMR patients with and without subclinical giant cell arteritis, and the prognostic role of imaging with respect to aneurysm development. Hence, in GCA and PMR, imaging stratification is hypothesized to be able to guide management strategies. With an established infrastructure within rheumatology for clinical studies in Denmark, the infrastructure of the Danish Rheumatologic Biobank, and the possibility to cross-link data with valid nationwide registries, the DANIVAS project holds an exceptional possibility to collect comprehensive real-world data on diagnosis, disease severity, disease duration, treatment effect, complications, and adverse events. In this paper, we present the research protocol for the DANIVAS study. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT05935709.

Erosive Progression by High-Resolution Peripheral Quantitative Computed Tomography and Conventional Radiography in Rheumatoid Arthritis.

OBJECTIVES: To investigate the diagnostic accuracy of high-resolution peripheral quantitative computed tomography (HR-pQCT) to assess erosive progression during one year compared to conventional radiography (CR) in rheumatoid arthritis (RA). METHODS: This prospective study included 359 patients with RA (disease duration ≥ 5 years) between March 2018 and October 2020. HR-pQCT and CR were obtained at inclusion and after one year. Erosive assessment was performed at two metacarpophalangeal joints of the dominant hand using HR-pQCT and progression was defined as an increase in erosion number ≥ 1 or an increase in erosive volume > least significant change. CR of hands, wrists, and feet were evaluated using Sharp/van der Heijde scores and erosive progression was defined as a 1.1-point increase in erosion score according to the smallest detectable change. RESULTS: In paired analyses (n = 310), erosive progression was identified in 30 patients using CR and in 40 patients using HR-pQCT. In the 40 patients with erosive progression on HR-pQCT, progression was not identified by CR in 33 patients. Adding HR-pQCT to CR doubled the proportion of patients identified with progression from 30 (10%) to 63 (20%) patients. Using CR as the reference, the sensitivity (% (95% CI)) of HR-pQCT for identifying erosive progression was 23.3 (9.9-42.3) and the specificity was 88.2 (83.8-91.7). CONCLUSION: A substantial proportion of patients with erosive progression are overlooked using CR only to monitor erosive progression. Adding high-resolution peripheral CT to CR doubles the proportion of patients, who may benefit from individualised therapy targeting erosive progression in RA.

Ultrasonography in the assessment of disease activity in cranial and large-vessel giant cell arteritis: a prospective follow-up study.

OBJECTIVES: We evaluated sensitivity to change and discriminative abilities of vascular US scores in disease monitoring in the follow-up of a prospective cohort of new-onset cranial and large-vessel (LV) GCA patients. METHODS: Baseline and follow-up (8 weeks, 24 weeks and 15 months) US of temporal arteries (TA), carotid and axillary arteries (LV) included assessment of halo and measurement of the intima media complex (IMC). Max IMC, max halo IMC, sum IMC, sum halo IMC, mean IMC, halo count and the Southend halo score were calculated. The provisional OMERACT US score, OGUS, was obtained, taking the average of temporal arteries and axillary arteries IMCs divided by their normal cut-off values. RESULTS: Baseline US was positive in 44/47 patients (72% TA, 72% LV). Sensitivity to change of all composite US scores containing TAs was evident by week 8 onward. LVs responded poorly and new axillary US lesions emerged in six patients despite clinical remission. The OGUS showed a large magnitude of change and is considered the score least prone to potential bias. All TA-based US scores showed moderate-strong correlation with disease activity markers. OGUS, TA halo count, Southend TA halo score, TA sum IMC and TA mean IMC showed potential to discriminate remission and relapse with area under the curve ≥0.8. CONCLUSIONS: The OGUS is suggested as an outcome measurement for the assessment of treatment response in clinical trials. The abilities of US scores to discriminate remission and relapse are encouraging and should be further explored.

Smartphone Pedometer Sensor Application for Evaluating Disease Activity and Predicting Comorbidities in Patients with Rheumatoid Arthritis: A Validation Study.

Smartphone-based pedometer sensor telemedicine applications could be useful for measuring disease activity and predicting the risk of developing comorbidities, such as pulmonary or cardiovascular disease, in patients with rheumatoid arthritis (RA), but the sensors have not been validated in this patient population. The aim of this study was to validate step counting with an activity-tracking application running the inbuilt Android smartphone pedometer virtual sensor in patients with RA. Two Android-based smartphones were tested in a treadmill test-bed setup at six walking speeds and compared to manual step counting as the gold standard. Guided by a facilitator, the participants walked 100 steps at each test speed, from 2.5 km/h to 5 km/h, wearing both devices simultaneously in a stomach pouch. A computer automatically recorded both the manually observed and the sensor step count. The overall difference in device step counts versus the observed was 5.9% mean absolute percentage error. Highest mean error was at the 2.5 km/h speed tests, where the mean error of the two devices was 18.5%. Both speed and cadence were negatively correlated to the absolute percentage error, which indicates that the greater the speed and cadence, the lower the resulting step counting error rate. There was no correlation between clinical parameters and absolute percentage error. In conclusion, the activity-tracking application using the inbuilt Android smartphone pedometer virtual sensor is valid for step counting in patients with RA. However, walking at very low speed and cadence may represent a challenge.

Fast track clinic for early diagnosis of polymyalgia rheumatica: Impact on symptom duration and prednisolone initiation.

OBJECTIVES: To evaluate the efficacy of a fast track clinic (FTC) for patients suspected of polymyalgia rheumatica (PMR) regarding symptom duration, prednisolone initiation before rheumatological assessment, number of hospital contacts before diagnosis, and cancer diagnosis. METHODS: It is a retrospective cohort study with a one year follow-up period. Patients referred to the FTC (1st August 2016 to 25th June 2019) were compared to a historical cohort of PMR patients (1st August 2014 to 1st August 2016). Referral criteria are: age over 50, symptoms of PMR but not cranial GCA, and increased C-reactive protein. Data were obtained from patient journals. RESULTS: Ninety-seven PMR patients in the historical cohort and 113 FTC patients, of whom 83 patients had PMR, were included. The median (interquartile range) number of days from symptom onset until PMR diagnosis were 53 (31-83) days in the FTC versus 80 (58-132) days in the historical cohort (P<0.001). Prednisolone was prescribed before rheumatological assessment to 11% in the FTC versus 42% in the historical cohort (P<0.001). Patients in the FTC had significantly fewer contacts with the hospital before the diagnosis compared with the historical cohort. Four patients in the FTC were diagnosed with a cancer, all of which were found by imaging. CONCLUSION: The FTC reduced the time from symptom onset until diagnosis, lowered prednisolone initiation before rheumatological assessment, and resulted in fewer hospital visits. The frequency of cancers was low in patients suspected of PMR and cancers were discovered by imaging.

The effect of a nurse-led prednisolone tapering regimen in polymyalgia rheumatica: a retrospective cohort study.

The objective of this study is to investigate the efficacy of a nurse-led prednisolone tapering regime in patients with polymyalgia rheumatica (PMR) compared to standard care. It is a single-center retrospective cohort study evaluating dose and percentage of patients receiving prednisolone after 1 and 2 years. A nurse-led PMR clinic was introduced June 2015 and patients diagnosed until June 2017 were included. Patients were diagnosed by a rheumatologist, and subsequently managed by nurses according to a specific protocol. Patients diagnosed with PMR between June 2012 and June 2015 served as controls. They received standard care by a rheumatologist. Sixty-eight patients received standard care and 107 nurse-led care. After 1 year, 71% of patients receiving standard care vs. 64% receiving nurse-led care took prednisolone (p = 0.441). Median (interquartile range) prednisolone dose after 1 year was 3.75 mg (0-5) in the standard care group and 1.25 mg (0-3.75) in the nurse-led care group (p = 0.004). After 2 years, 41% of patients receiving standard care vs. 18% receiving nurse-led care took prednisolone (p = 0.003). Prednisolone dose after 2 years was 0 mg (0-2.5) in the standard care group and 0 mg (0-0) in the nurse-led care group (p = 0.004). There was no difference regarding relapse and initiation of methotrexate. The number of patient contacts was 12.5 (5-16.5) in the standard care group vs. 17 (13-23) in the nurse-led care group (p = 0.001). A tight and systematic approach to prednisolone tapering is more effective than standard care, but more frequent patient contacts were necessary to obtain this effect.