Relapse after cessation of weekly tocilizumab for giant cell arteritis: a multicentre service evaluation in England
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Issue Date
2024
Type
Scientific Paper
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Keywords
Research Subject Categories::MEDICINE::Dermatology and venerology,clinical genetics, internal medicine::Internal medicine::Rheumatology
Alternative Title
Abstract
Abstract
Objectives
The National Health Service in England funds 12 months of weekly s.c. tocilizumab (qwTCZ) for patients with relapsing or refractory GCA. During the coronavirus disease 2019 (COVID-19) pandemic, some patients were allowed longer treatment. We sought to describe what happened to patients after cessation of qwTCZ.
Methods
Multicentre service evaluation of relapse after stopping qwTCZ for GCA. The log-rank test was used to identify significant differences in time to relapse.
Results
A total of 336 GCA patients were analysed from 40 centres, treated with qwTCZ for a median [interquartile range (IQR)] of 12 (12–17) months. At time of stopping qwTCZ, median (IQR) prednisolone dose was 2 (0–5) mg/day. By 6, 12 and 24 months after stopping qwTCZ, 21.4%, 35.4% and 48.6%, respectively, had relapsed, requiring an increase in prednisolone dose to a median (IQR) of 20 (10–40) mg/day. 33.6% relapsers had a major relapse as defined by EULAR. Time to relapse was shorter in those that had previously also relapsed during qwTCZ treatment (P = 0.0017), in those not in remission at qwTCZ cessation (P = 0.0036) and in those with large vessel involvement on imaging (P = 0.0296). Age ≥65 years, gender, GCA-related sight loss, qwTCZ treatment duration, TCZ taper, prednisolone dosing and conventional synthetic DMARD use were not associated with time to relapse.
Conclusion
Up to half our patients with GCA relapsed after stopping qwTCZ, often requiring a substantial increase in prednisolone dose. One-third of relapsers had a major relapse. Extended use of TCZ or repeat treatment for relapse should be considered for these patients.
graphic
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giant cell arteritis, vasculitis, tocilizumab, NICE guidance, service evaluation, relapse
Topic: giant cell arteritisfollow-upprednisolonediagnostic imagingpandemicstocilizumabdisease remissionlarge blood vesselsnational health service (uk)
Issue Section: Clinical Science
Rheumatology key messages
Up to half of patients relapsed after stopping tocilizumab; one in three relapses were major.
Relapses after stopping tocilizumab required a substantial increase in prednisolone dose.
Patients who had already relapsed during tocilizumab therapy were more likely to relapse after stopping.
Introduction
GCA is a primary systemic vasculitis treated with long-term glucocorticoid to prevent ischaemic complications such as visual loss [1]. Relapses require treatment escalation [2], which can cause significant glucocorticoid toxicity [3]. Weekly s.c. tocilizumab (qwTCZ) is licensed for GCA on the basis of clinical trial evidence of reduced relapse rate and cumulative glucocorticoid requirements [4, 5].
Following approval by the National Institute for Health and Care Excellence (NICE), 12 months of treatment with TCZ for patients with refractory or relapsing GCA has been available through the English National Health Service (NHS) since July 2018 (Technology Appraisal TA518) [6] (see Supplementary Fig. S1, available at Rheumatology online, for definitions of refractory and relapsing). Treatment beyond 12 months is not currently funded in England. From July 2020, during the coronavirus disease 2019 (COVID-19) pandemic, NHS England permitted >12 months of treatment for GCA patients believed to be at higher risk of relapse [large vessel (LV)-GCA on imaging or biopsy, history of critical ischaemia or active disease between months 6 and 12 on TCZ with eventual disease control]; this arrangement ceased on 31 March 2022.
We designed a multicentre service evaluation to describe clinical outcomes after qwTCZ cessation in patients with GCA in England, focusing on the time to first relapse.
Methods
Inclusion criteria
From November 2022 to January 2023, NHS rheumatology departments (centres) in England were invited to take part in TOC STOP by submitting anonymized data on all their GCA patients who had completed at least one month of qwTCZ and had at least one follow-up after qwTCZ had been stopped. Follow-up started when qwTCZ was stopped. One dose of i.v. TCZ 8 mg/kg was considered equivalent to 4 weeks of s.c. TCZ 162 mg/week.
Data collection and information governance
Approval from an ethics committee and patient consent were not required as TOC STOP was defined as a service evaluation with the Health Research Authority decision tool following advice from the Chair of the Oxford A (UK) Research Ethics Committee. Each participating centre registered TOC STOP with their audit department, identified relevant patients using local databases and reviewed their patients’ medical records. Data were recorded on a standardized Microsoft Excel spreadsheet, supported by a Frequently Asked Questions list generated during a pilot of 62 patients conducted at two participating centres (Luton and Leeds). To minimize the risk of inadvertent patient identification and for reasons of feasibility and parsimony, data collection was kept to core variables, all durations were rounded to nearest month, and the only patient demographics collected were gender and age ≥65 years. Each centre obtained local Caldicott Guardian approval to export their anonymized data to Luton and Dunstable Hospital, UK, for amalgamation. All identifiable data were removed before export. Data queries were completed and centre identifiers removed to create the final dataset for analysis.
Definitions
Remission was defined as absence of signs or symptoms of GCA with centre-defined normal laboratory markers of inflammation (CRP, ESR or plasma viscosity).
Relapse was either documented by a consultant or confirmed by consultant review of the medical notes, and defined as an increase in disease activity of sufficient severity to require a change of treatment plan such as slowed glucocorticoid taper, glucocorticoid dose increase or addition of conventional synthetic DMARD (csDMARD). This definition allowed inclusion of those not in remission at qwTCZ cessation, who may still have responded over their treatment course: GCA disease states are not binary; there exists a continuum where patients are neither in full remission nor in acute relapse, e.g. stable low disease activity. Time of relapse was defined as time of treatment plan change, rounded to the nearest month.
Major relapse was defined as relapse with clinical features of ischaemia, e.g. jaw claudication, visual symptoms, visual loss, scalp necrosis, stroke, limb claudication and/or evidence of active aortic inflammation causing progressive aortic or large vessel stenosis, dilatation or dissection [7]; and could occur at any time during follow-up.
LV-GCA was defined as GCA involving the aorta and/or its major branches such as the axillary, subclavian or carotid arteries, and confirmed by imaging at any time since diagnosis (wall thickening, oedema, increased tracer uptake or stenosis deemed to be due to vasculitis). Cranial GCA could include headache, scalp tenderness, jaw or tongue claudication, scalp necrosis or abnormality of temporal arteries on examination, biopsy or imaging. GCA phenotype was classified as pure cranial, pure LV-GCA or mixed (both cranial and LV-GCA).
csDMARD was defined as any of oral/s.c. MTX, LEF, AZA, MMF or CYC given for GCA. Specific csDMARDs were not collected.
Optional variables, if collected by a centre, were required for all patients submitted by that centre; these included GCA relapse whilst on qwTCZ and death during follow-up.
For the purpose of this analysis, patients were deemed to fulfil the pandemic extension criteria if they had at least one of LV-GCA, GCA-related sight loss or GCA relapse whilst on qwTCZ.
Statistical analysis
Categorial variables were shown as numbers and percentages. Continuous variables were shown as the median with IQR, as the data were not normally distributed. Baseline characteristics of relapsers and non-relapsers after qwTCZ cessation were compared with the two-tailed Z-test or non-parametric t-test to identify variables of interest for time to first relapse analysis.
In further data exploration, correlations between variables were analysed with polyserial (categorical vs continuous variables) or tetrachoric correlation (categorical vs categorical variables).
For time to first relapse analysis, we plotted Kaplan–Meier curves with 95% Hall–Wellner bands. We also plotted curves for variables of interest identified a priori or from the data exploration phase. A log-rank test was used to compare time to relapse between subgroups.
In an exploratory multivariable analysis, we fitted a Cox proportional-hazard model to investigate the association between relapse after qwTCZ cessation and a number of variables.
A P-value <0.05 was considered statistically significant. Statistical analysis was performed with SAS version 9.4.
Results
Data from 379 patients from 40 centres across England were submitted. Centres submitted a median of 5 (IQR 2–12) patients; 7 centres submitted 20 or more.
Forty-three patients were excluded from the analysis: 23/43 did not fulfil the inclusion criteria as they had no follow-up after qwTCZ cessation, whilst 20/43 had commenced TCZ treatment before publication of NICE TA518 [5] so criteria for commencement and cessation may have differed. A total of 336 patients remained for the analysis. There were no missing values in the compulsory dataset.
Patients and treatments up to the time of stopping qwTCZ
Patient characteristics are shown in Table 1, which also includes a comparison between those with and without GCA relapse after qwTCZ cessation. 61.3% patients had evidence of LV-GCA on imaging during their disease course, likely reflecting a propensity for LV involvement in relapsing/refractory patients; 43.2% were co-prescribed a csDMARD during the last 3 months of qwTCZ.
Table 1.Open in new tabBaseline characteristics of the whole cohort and according to relapse after qwTCZ cessation
All patients in analysis (n = 336) Relapsed after stopping qwTCZ (n = 110) No relapse after stopping qwTCZ (n = 226) P (between relapsers and non relapsers)
Demographics, phenotype and baseline features
Age 65 years or older, n/N (%) 301/336 (89.6) 95/110 (86.4) 206/226 (91.2) 0.1777
Female, n/N (%) 226/336 (67.3) 71/110 (64.5) 155/226 (58.3) 0.4593
GCA visual loss, n/N (%) 71/336 (21.1) 18/110 (16.4) 53/226 (23.5) 0.1353
Cranial features of GCA, n/N (%) 294/336 (87.5) 95/110 (86.4) 199/226 (88.1) 0.6604
LV-GCA, n/N (%) 206/336 (61.3) 78/110 (70.9) 128/226 (56.6) 0.0117
Pure cranial GCA (cranial features only, no LV-GCA), n/N (%) 130/336 (38.7) 32/110 (29.1) 98/226 (43.4) 0.0117
Pure LV-GCA (LV-GCA only, no cranial features), n/N (%) 43/336 (12.8) 15/110 (13.6) 28/226 (12.4) 0.7482
Mixed GCA (cranial and LV-GCA), n/N (%) 163/336 (48.5) 63/110 (57.3) 100/226 (44.2) 0.0250
csDMARD before TCZ, n/N (%) 190/336 (56.5) 70/110 (63.6) 120/226 (53.1) 0.0674
Daily prednisolone equivalent dose when qwTCZ started, median (IQR), mg 20 (10–40) 20 (10–40) 20 (10–40) 0.3684
During TCZ therapy
csDMARD during qwTCZ, n/N (%) 145/336 (43.2) 44/110 (40) 101/226 (44.7) 0.4153
GCA relapse during qwTCZa, n/N (%) 47/285 (16.5) 24/93 (25.8) 23/192 (12) 0.0032
Pandemic extension criteriaa, n/N (%) 227/285 (79.6) 77/93 (82.8) 150/192 (78.1) 0.3585
GCA in remission at cessation of qwTCZ, n/N (%) 286/336 (85.1) 83/110 (75.5) 203/226 (89.8) 0.0005
Daily prednisolone equivalent dose at qwTCZ cessation, median (IQR), mg 2 (0–5) 2.5 (0–5) 1 (0–5) 0.2153
Duration of TCZ therapy
qwTCZ duration, median (IQR), months 12 (12–17) 12 (11–16) 12 (12–17) 0.1996
Total TCZ duration, median (IQR), months 13 (12–19) 13 (11.9–17.1) 14 (12–19) 0.0626
Proportion that tapered TCZ dose, n/N (%) 57/336 (17.0) 20/110 (18.2) 37/226 (16.4) 0.4060
TCZ taper duration average for those that tapered, median (IQR), months 6 (2–13) 3 (2–7) 7 (3–15) 0.0758
After TCZ cessation
csDMARD after qwTCZ cessation, n/N (%) 182/336 (54.2) 63/110 (57.3) 119/226 (52.7) 0.4253
GCA relapse after qwTCZ cessation, n/N (%) 110/336 (32.7) 110/110 (100) 0/226 (0) NA
Major relapse after qwTCZ cessation, n/N (%) 37/336 (11.0) 37/110 (33.6) 0/0 (0) NA
Maximum prednisolone dose used to treat GCA relapse after qwTCZ cessation, median (IQR), mg 20 (10–40) 20 (10–40) NA NA
Duration of follow-up after qwTCZ cessation, median (IQR), months 10 (5–18) 15 (8–24) 8 (4–16) 0.0001
Last documented prednisolone dose for GCA, median (IQR), mg 2.5 (0–6) 6 (3–15) 0 (0–5) 0.0001
GCA visual loss: permanent visual loss from GCA-related ocular ischaemic event such as anterior ischaemic optic neuropathy or central retinal artery occlusion. csDMARD before TCZ: any of MTX, s.c. MTX, LEF, AZA, MMF or CYC for GCA at any time before TCZ was started. csDMARD during qwTCZ: on any csDMARD listed above in last 3 months of qwTCZ. csDMARD after cessation of qwTCZ: on any csDMARD listed above for GCA at any time during the first 4 weeks after qwTCZ cessation. Maximum prednisolone dose used to treat GCA relapse after qwTCZ cessation: highest daily prednisolone dose used to treat any GCA relapse that occurred after qwTCZ cessation. Last documented prednisolone dose for GCA: daily prednisolone equivalent dose given for GCA at the time of the last documented follow-up. For other definitions see methods section of the report.
a
Optional question (or includes optional question) completed for 285/336 (84.8%) of the cohort. P-value for difference between relapsers and non-relapsers was determined by two-tailed Z Test or non-parametric t-test. Bold text indicates statistically significant P-values (P <0.05). TCZ: tocilizumab; qwTCZ: weekly s.c. tocilizumab; LV-GCA: large vessel GCA; IQR: interquartile range; csDMARD: conventional synthetic DMARD.
Median prednisolone dose at start of treatment with qwTCZ was 20 (10–40) mg/day, and 2 (0–5) mg/day at qwTCZ cessation (P = 0.0001).
Median duration of qwTCZ was 12 (12–17) months. A total of 78/336 (23.2%) patients received <12 months, 96/336 (28.6%) received 12 months and 162/336 (48.2%) received >12 months qwTCZ (Supplementary Graph S1, available at Rheumatology online).
286/336 (85.1%) patients were in remission at the time they stopped qwTCZ. For the patients where these optional data were collected, 47/285 (16.5%) patients had relapsed whilst receiving qwTCZ.
Treatments during follow-up after qwTCZ cessation
Median duration of follow-up after qwTCZ cessation was 10 (5–18) months (Supplementary Graph S2, available at Rheumatology online.).
After cessation of qwTCZ, 57/336 (17.0%) ‘tapered’ their TCZ treatment by taking it at intervals >1 week. Therefore, 17% patients took tapered dose TCZ for a proportion of their follow-up (as follow-up started when qwTCZ was stopped). Median duration of tapered TCZ was 6 (2–13) months; 41/57 patients took tapered TCZ for 3 months or more. Median duration of qwTCZ in those that tapered was 12 (7–16.5) months.
Reflecting prescribing patterns in England, 53.3% received a csDMARD during the first 4 weeks after cessation of qwTCZ.
Relapse during follow-up after qwTCZ cessation
A total of 110/336 patients (32.7%) relapsed after stopping qwTCZ. Of these, 37/110 (33.6%) had a major relapse, representing 11.0% (37/336) of analysed patients. Median peak prednisolone dose used to treat relapse after qwTCZ cessation was 20 (10–40) mg/day. In those with major relapse, median peak prednisolone dose was 30 (15–60) mg/day. As expected, those that relapsed after stopping qwTCZ had been followed up for longer than non-relapsers. Where these optional data were collected, 17/301 (5.65%) died during the follow-up period after qwTCZ cessation.
Relapse after qwTCZ cessation occurred in 52/243 (21.4%), 55/155 (35.4%), 45/100 (45.0%) and 35/72 (48.6%) of those followed up for 6, 12, 18 and 24 months, respectively (Kaplan–Meier curve, Fig. 1A). Time to relapse was significantly shorter in those with LV-GCA (P = 0.0296) (Fig. 1B), in those who had relapsed during qwTCZ (P = 0.0017) (Fig. 1C) and in those not in remission at qwTCZ cessation (P = 0.0036) (Fig. 1D).
Kaplan–Meier survival curves for time to GCA relapse after qwTCZ cessation with number of patients at risk and 95% Hall–Wellner bands. All 336 patients, regardless of disease activity state at cessation of qwTCZ, were included in this analysis. Patients were censored if they had not relapsed by the time their follow-up ended. TCZ: tocilizumab, LV-GCA: large vessel GCA
Figure 1.Kaplan–Meier survival curves for time to GCA relapse after qwTCZ cessation with number of patients at risk and 95% Hall–Wellner bands. All 336 patients, regardless of disease activity state at cessation of qwTCZ, were included in this analysis. Patients were censored if they had not relapsed by the time their follow-up ended. TCZ: tocilizumab, LV-GCA: large vessel GCA
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There was no clear relationship between time to relapse and qwTCZ duration, TCZ tapering or csDMARD use (Supplementary Fig. S1E–H, available at Rheumatology online).
20/57 (35.1%) patients that tapered TCZ relapsed after stopping qwTCZ. 12/57 (21.1%) relapsed whilst on their TCZ taper.
Exploratory descriptive correlations and multivariable Cox regression are shown in Supplementary Tables S1 and S2, available at Rheumatology online.
Status at last follow-up
Patients who had relapsed following qwTCZ cessation were taking a higher dose of prednisolone at last follow-up than those who had not relapsed [median 6 (3–15) mg/day vs 0 (0–5) mg/day].
Discussion
In this multicentre service evaluation of 336 patients who received qwTCZ for relapsing or refractory GCA, 35.4% had relapsed by 1 year and 48.6% by 2 years after qwTCZ cessation, requiring substantial prednisolone dose escalation back to ranges comparable to those taken at the start of TCZ treatment: median 20 (10–40) mg/day. 33.6% relapsers had a major relapse. Time to relapse was shorter for those who had relapsed during qwTCZ therapy although this was an optional variable collected in only 85% patients. Time to relapse was shorter for those with LV involvement, although as we allowed LV-GCA to be detected at any time, there may have been more vascular imaging in relapsing patients compared with non-relapsers. Finally, time to relapse was shorter in patients who were not in remission at qwTCZ cessation.
Age ≥65 years, gender, GCA-related sight loss, qwTCZ treatment duration, TCZ taper, prednisolone dosing and csDMARD use were not associated with relapse, in contrast to some previous reports [2, 8–13]. However, patient heterogeneity and variations in clinical practice in our non-randomized evaluation may have obscured a real association (e.g. extended duration TCZ was restricted to those fulfilling criteria believed to be associated with relapse, and GCA monitoring/treatment practices may have changed during/after COVID-19-related local and national lockdowns).
The strengths of this study include the large representative sample. Feasibility and generalizability were maximized by the strong incentive to keep accurate lists of GCA patients prescribed TCZ to ensure central reimbursement; the standardized prescribing mandated by NHS England; and the focused data collection.
Our definition of relapse (worsening of disease activity requiring treatment change) was less restrained than EULAR’s (return of disease activity) [7], and patients were selected for severity as NHS England restricts TCZ to relapsing or refractory GCA [6]. Despite this, our relapse rate of ∼50% at 2 years was similar to meta-analyses of GCA patients treated with glucocorticoid alone [14] and MTX [2], the open label extension of the Giant-Cell Arteritis Actemra (GiACTA) trial [15] and other TCZ studies [12, 16, 17]. However, major relapse occurred more often (11.0%) than was reported in a meta-analysis of 2745 GCA patients (3.3%) [18].
Limitations of the retrospective design and reliance on clinical records meant that some variables, such as cumulative prednisolone dose, were not possible to calculate. Other than death, reasons for loss to follow-up were also not collected, nor did we collect data on reasons for early qwTCZ cessation or TCZ tapering, where this occurred.
In conclusion, TOC STOP provides descriptive real-world data on GCA patient outcomes in England after qwTCZ cessation. Relapse occurred in up to half of patients requiring a substantial increase in prednisolone dose. These data challenge the concept of GCA as a self-limiting disease and support a change to NHS England policy such as extended use of TCZ for GCA beyond 12 months or repeat treatment for GCA relapse.
Supplementary material
Supplementary material is available at Rheumatology online.
Data availability
The anonymized data underlying this article will be shared upon reasonable request to the corresponding author.
Funding
No specific funding was received from any bodies in the public, commercial or not-for-profit sectors to carry out the work described in this article.
Disclosure statement: V.Q. has received honoraria for educational and/or advisory services or travel support from Novartis, Abbvie, Pfizer and Roche, and is a Trustee of the Charity PMRGCAuk. M.A. has received honoraria for educational services and support to attend national and international meetings from Chugai, Abbvie, UCB, Pfizer and Janssen. M.B. has been sponsored to attend regional, national and international meetings by UCB celltech, Roche/Chugai, Pfizer, Abbvie, Merck, Mennarini, Janssen, Bristol-Myers Squib, Novartis and Eli-Lilly. He has received honoraria for speaking and attended advisory boards with Bristol-Myers Squib, UCB celltech, Roche/Chugai, Pfizer, Abbvie, Merck, Mennarini, Sanofi-aventis, Eli-Lilly, Janssen, Amgen, Novartis and Gilead. S.D. has received honoraria for educational and advisory services from Janssen and Boehringer-Ingelheim. N.G. has received research funding from AbbVie, AstraZeneca, Lilly and Novartis, and speaker fees/honoraria from AbbVie, Janssen, Lilly, Novartis and UCB; sponsorship for national and international meeting has been provided by Janssen, Lilly, Novartis and UCB. J.H. has received support for international meeting attendance from CSL Vifor. M.H. has received speaker fees from Abbvie. A.K. has received speaker fees from Galapagos and Novartis and consultancy fees from Novartis. L.M. as been sponsored to attend national and international meetings by UCB, Abbvie, Nordic Pharma. S.L.M. reports: consultancy on behalf of her institution for Roche/Chugai, Sanofi, AbbVie, AstraZeneca, Pfizer; Investigator on clinical trials for Sanofi, GSK, Sparrow; speaking/lecturing on behalf of her institution for Roche/Chugai, Vifor, Pfizer, UCB and Novartis; chief investigator on STERLING-PMR trial, funded by the National Institute for Health and Care Research (NIHR); patron of the charity PMRGCAuk. No personal remuneration was received for any of the above activities. Support from Roche/Chugai to attend EULAR2019 in person and from Pfizer to attend ACR Convergence 2021 virtually. S.L.M. is supported in part by the NIHR Leeds Biomedical Research Centre. The remaining authors have declared no conflicts of interest. The views expressed in this article are those of the authors and not necessarily those of the NIHR, the NIHR Leeds Biomedical Research Centre, the National Health Service or the UK Department of Health and Social Care.
Acknowledgements
We would like to thank Hugh Davies, Chair of the Oxford A Research Ethics Committee, Oxford UK, for his advice during the development of the evaluation protocol. We also thank Stephen Sah, of Luton and Dunstable Hospital NHS Foundation Trust and Hammersmith Medicines Research, London, UK, for statistical support.
The TOC STOP 2022 Investigators: Saad Ahmed, Rheumatology Department, Colchester Hospital University NHS Foundation Trust, Colchester, UK; Ismael Atchia, Rheumatology Department, Northumbria Healthcare NHS Trust, Northumberland, UK; James Bluett, Rheumatology Department, Pennine MSK Partnership Ltd, Integrated Care Centre, Oldham, UK and Versus Arthritis Centre for Genetics and Genomics, Centre for Musculoskeletal Research, University of Manchester, Manchester, UK; Alex Connew, Rheumatology Department, Furness General Hospital, Barrow in Furness, UK; Elizabeth Coulson, Rheumatology Department, Northumbria Healthcare NHS Trust, Northumberland, UK; Helena Crawshaw, Rheumatology Department, Gloucestershire Royal Hospital NHS Foundation Trust, Gloucester, UK; Ursula Davies, Rheumatology Department, Surrey and Sussex Healthcare NHS Trust, UK; Denise De Lord, Rheumatology Department, East Kent Hospitals University NHS Foundation Trust, Kent, UK; Gurdeep Dulay, Rheumatology Department, Portsmouth Hospitals University NHS Trust, Portsmouth, UK; Amanda Embuldeniya, Rheumatology Department, Surrey and East Sussex Healthcare NHS Trust, UK; Carmen Fonseca Rheumatology Department, Whittington Health NHS Trust, London, UK; James Galloway, Rheumatology Department, King’s College London, London, UK; William Gubbins, Rheumatology Department, Portsmouth Hospitals University NHS Trust, Portsmouth, UK; Thushyanthan Guruparan, Rheumatology Department, Isle of White NHS Trust, Isle of White, UK; Rebecca Heaton, Rheumatology Department, Stockport NHS Foundation Trust, Stockport, UK; Martin James, Rheumatology Department, Royal Devon University Healthcare NHS Foundation Trust, Devon, UK; Shalini Janagan, Rheumatology department, Bristol Royal Infirmary, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK; Hilary Johnson, Rheumatology Department, Gloucestershire Royal Hospital NHS Foundation Trust, Gloucester, UK; Areej Karim, Rheumatology Department, Manchester University NHS Foundation Trust, Manchester, UK; Salema Khalid, Rheumatology Department, Salisbury NHS Foundation Trust, Salisbury, UK; Kath Kinsey, Rheumatology Department, Pennine MSK Partnership Ltd, Integrated Care Centre, Oldham, UK; Gouri Koduri, Rheumatology Department, Southend University Hospital NHS Trust, Southend, UK; Stuart Linton, Rheumatology Department, Isle of Wight NHS Trust, St Mary’s Hospital, Parkhurst Road, Newport, UK; Elizabeth MacPhie, Rheumatology Department, Lancashire & South Cumbria NHS Foundation Trust, UK; Arti Mahto, Rheumatology Department, Kings College Hospital NHS Foundation Trust, London, UK; Chetan Mukhtyar, Vasculitis Service, Rheumatology Department, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK; Anupama C. Nandagudi, Rheumatology Department, Mid and South Essex NHS Foundation Trust; Pradip Nandi, Rheumatology Department, Northampton General Acute NHS Trust, Northampton, UK; Fathelrahman Osman, Rheumatology Department, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK; Sophie Plumb, Rheumatology Department, Wye Valley NHS Trust, Hereford, UK; Eavan Quinlan, Rheumatology Department, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK; Angela Redfern, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK; Marian Regan, Rheumatology Department, University Hospitals of Derby and Burton NHS Foundation Trust, Derby, UK; Vanessa Reid, Rheumatology Department, Manchester Royal Infirmary, Manchester University Foundation NHS Trust, Manchester, UK; Dipak Roy, Rheumatology Department, Tameside & Glossop Integrated Care NHS Foundation Trust, Ashton-under-Lyne, UK; Sadaf Saeed, Rheumatology Department, North Bristol NHS Trust, Bristol, UK; Abbey Smith, Rheumatology Department, The Newcastle upon Tyne Hospitals NHS Foundation Trust, UK; Lauren Steel, Rheumatology Department, Colchester Hospital University NHS Foundation Trust, Colchester, UK; Rhys Thomas, Rheumatology Department, Whittington Health NHS Trust, London, UK; Adaeze Ugwoke, Department of Rheumatology, Addenbrooke’s Hospital, Cambridge University Hospitals, Cambridge, UK; Sarah Villar, North Bristol NHS Trust, Bristol, UK; Emma Williams, Rheumatology Department, Royal Hampshire County Hospital, Hampshire, UK; Fiona Wood, Rheumatology Department, Furness General Hospital, Barrow in Furness, UK; Mingrui Xie, Rheumatology Department, University College London NHS Foundation Trust, London, UK.
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Author notes
See the Acknowledgements for a list of the TOC STOP 2022 Investigators.
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Vanessa Quick, Mahdi Abusalameh, Sajeel Ahmed, Hoda Alkoky, Marwan Bukhari, Stuart Carter, Fiona L Coath, Brian Davidson, Parveen Doddamani, Shirish Dubey, Georgina Ducker, Bridget Griffiths, Nicola Gullick, Jonathan Heaney, Amelia Holloway, Ei Ei Phyu Htut, Mark Hughes, Hannah Irvine, Alison Kinder, Asim Kurshid, Joyce Lim, Dalia R Ludwig, Mariam Malik, Louise Mercer, Ben Mulhearn, Jagdish R Nair, Rikesh Patel, Joanna Robson, Pratyasha Saha, Sarah Tansley, the TOC STOP 2022 Investigators , Sarah L Mackie, Relapse after cessation of weekly tocilizumab for giant cell arteritis: a multicentre service evaluation in England, Rheumatology, Volume 63, Issue 12, December 2024, Pages 3407–3414, https://doi.org/10.1093/rheumatology/kead604