Salvarani C, Crowson CS, O'Fallon WM, Hunder GG, Gabriel SE.
Reappraisal of the epidemiology of giant cell arteritis in Olmsted County, Minnesota, over a fifty-year period.
Arthritis Rheum. 2004 Apr 15;51(2):264-8. doi: 10.1002/art.20227.
Abstract/Text
OBJECTIVE: To investigate time trends in the incidence and survival of giant cell arteritis (GCA) over a 50-year period in Olmsted County, Minnesota.
METHODS: Using the unified record system at the Mayo Clinic, we identified all incident cases of GCA first diagnosed between 1950 and 1999. Incidence rates were estimated and adjusted to the 1980 United States white population for age and sex. The annual incidence rates were graphically illustrated using a 3-year centered moving average. Survival rates were computed and compared with the expected rates in the population.
RESULTS: There were 173 incident cases of GCA during the 50-year study period. Of these, 79% were women and the mean age at diagnosis was 74.8 years. The overall age- and sex-adjusted incidence per 100,000 persons 50 years of age or older was 18.8 (95% confidence interval [95% CI] 15.9-21.6). Incidence was higher in women (24.4; 95% CI 20.3-28.6) than in men (10.3; 95% CI 6.9-13.6). Incidence rates increased significantly over the study period (P = 0.017); in particular, a progressive increase was observed from 1950 to 1979; subsequently, no substantial increases in incidence rates were observed. A cyclic pattern of annual incidence rates was apparent, with evidence of 6 peak periods. Survival among individuals with GCA was not significantly different from that expected in the population (P = 0.80).
CONCLUSIONS: The incidence of GCA increased over the first 3 decades of the study, then remained stable over the last 20 years. The previously observed cyclic pattern of annual incidence rates was still apparent over a 50-year period. Overall survival in GCA was similar to that in the population.
Gonzalez-Gay MA, Miranda-Filloy JA, Lopez-Diaz MJ, Perez-Alvarez R, Gonzalez-Juanatey C, Sanchez-Andrade A, Martin J, Llorca J.
Giant cell arteritis in northwestern Spain: a 25-year epidemiologic study.
Medicine (Baltimore). 2007 Mar;86(2):61-68. doi: 10.1097/md.0b013e31803d1764.
Abstract/Text
To continue our investigation of the epidemiology of giant cell arteritis (GCA) in southern Europe, we assessed the potential presence of trends, peaks, and fluctuations in the incidence of this vasculitis over a 25-year period in the Lugo region of northwestern Spain. We also sought to determine whether changes in the clinical spectrum of the disease existed. From 1981 to 2005, biopsy-proven GCA was diagnosed in 255 Lugo residents. The age- and sex-adjusted annual incidence rate was 10.13 (95% confidence interval [CI], 8.93-11.46) per 100,000 population aged 50 years and older. The mean age +/- SD at the time of diagnosis was 75.0 +/- 6.9 years. The annual incidence rate in women (10.23; 95% CI, 8.60-12.08) was slightly greater than that in men (9.92; 95% CI, 8.19-11.89) (p = 0.15). The annual incidence rate increased with advancing age up to a maximum of 23.16 (95% CI, 19.52-27.28) in the 70-79 year age-group. A progressive increase in the incidence was observed from 1981 through 2000 (p = 0.001). However, the age- and sex-adjusted incidence rate for biopsy-proven GCA in the Lugo region did not show peaks in the annual incidence of GCA. Likewise, we observed no seasonal pattern for the diagnosis of the disease. Visual ischemic manifestations and irreversible visual loss were observed in 57 (22.4%) and 32 (12.5%) of the 255 patients, respectively. A negative trend manifested by a progressive decline in the number of patients with visual ischemic manifestations (p = 0.021) or permanent visual loss (p = 0.018) was found over the 25-year period of study. The decline in the frequency of visual manifestations of GCA could not be attributed to a shorter delay to diagnosis, as no significant differences were observed when the delays to diagnosis in the 5 consecutive 5-year periods were compared. In conclusion, the current study confirms a progressive increase in the incidence of biopsy-proven GCA in northwestern Spain, and suggests that there has been a change in the clinical spectrum of the disease.
Knockaert DC, Vanneste LJ, Bobbaers HJ.
Fever of unknown origin in elderly patients.
J Am Geriatr Soc. 1993 Nov;41(11):1187-92. doi: 10.1111/j.1532-5415.1993.tb07301.x.
Abstract/Text
OBJECTIVE: To describe the spectrum of diseases that may give rise to fever of unknown origin in elderly patients and to delineate the diagnostic approach in these patients.
DESIGN: Subgroup analysis of a prospectively collected case series followed more than 2 years.
SETTING: General Internal Medicine Service based at University hospital, Leuven, Belgium.
PATIENTS: Forty-seven consecutive patients, older than 65 years, meeting the classic criteria of fever of unknown origin.
MEASUREMENTS: The final diagnosis established and the clinical value of diagnostic procedures.
RESULTS: Infections, tumors and multisystem diseases (encompassing rheumatic diseases, connective tissue disorders, vasculitis including temporal arteritis, polymyalgia rheumatica, and sarcoidosis) were found in 12 (25%), six (12%) and 15 patients (31%), respectively. Drug-related fever was the cause in three patients (6%), miscellaneous conditions were found in five patients (10%), and six patients (12%) remained undiagnosed. Microbiologic investigations were diagnostic in eight cases (16%), serologic tests yielded one diagnosis, immunologic investigations had a diagnostic value in four cases, standard X-rays yielded a diagnostic contribution in 10 cases, ultrasonography and computed tomography were diagnostic in 11 cases, Gallium scintigraphy had a diagnostic contribution in 17 cases, and biopsies yielded the final diagnosis in 18 cases.
CONCLUSIONS: Multisystem diseases emerged as the most frequent cause of fever of unknown origin in the elderly, and temporal arteritis was the most frequent specific diagnosis. Infections, particularly tuberculosis, remain an important group. The percentage of tumors was higher in our elderly patients than in the younger ones but still clearly lower than in other recent series of FUO in adults. The number of undiagnosed cases was significantly lower in elderly patients than in younger individuals (P < or = 0.01). The investigation of elderly patients with FUO should encompass routine temporal artery biopsy and extensive search for tuberculosis if the classic tests such as blood count, chemistry, urinalysis, cultures, chest X-rays, and abdominal ultrasonography do not yield any clue. Gallium scintigraphy should be considered as the next step and not as a last-resort procedure.
Larson TS, Hall S, Hepper NG, Hunder GG.
Respiratory tract symptoms as a clue to giant cell arteritis.
Ann Intern Med. 1984 Nov;101(5):594-7. doi: 10.7326/0003-4819-101-5-594.
Abstract/Text
Although many manifestations of giant cell arteries are increasingly recognized, little attention has been paid to respiratory symptoms associated with this disorder. We report the cases of 16 patients with giant cell arteritis who had prominent symptoms related to the respiratory tract including cough, sore throat, and hoarseness. These symptoms were the initial finding in 10 patients and obscured the diagnosis in some instances, but resolved quickly when corticosteroids were given. It is estimated that 9% of patients with giant cell arteritis have prominent respiratory tract symptoms, which are the initial manifestation in 4%. This disorder should be considered in an older patient with a new cough or throat pain without obvious cause.
Smetana GW, Shmerling RH.
Does this patient have temporal arteritis?
JAMA. 2002 Jan 2;287(1):92-101. doi: 10.1001/jama.287.1.92.
Abstract/Text
CONTEXT: Clinicians must be able to confidently diagnose temporal arteritis (TA), since failure to make a correct diagnosis may lead to irreversible visual loss as well as inappropriate evaluation and treatment of headache, fatigue, and other potential presenting symptoms. The diagnostic value of particular signs and symptoms among patients with suspected TA is unknown.
OBJECTIVE: To determine the accuracy of historical features, physical examination, and erythrocyte sedimentation rate (ESR) in diagnosis of TA.
DATA SOURCES: We performed a MEDLINE search of English-language articles published between January 1966 and July 2000 and a hand search of bibliographies of retrieved articles, previous reviews, monographs, and textbooks.
STUDY SELECTION: Studies that provided detailed clinical information on patients who had been referred for temporal artery biopsy. Of 114 studies retrieved, 41 met our inclusion criteria; 21 included both biopsy-positive and biopsy-negative patients and formed the core of our review.
DATA EXTRACTION: Both authors independently reviewed each study to determine eligibility, abstracted data using a standardized instrument, and classified study quality using predetermined criteria.
DATA SYNTHESIS: The prevalence of TA in the general population is less than 1%. However, in our 21 core studies, 39% of patients referred for temporal artery biopsy had positive results. The only 2 historical features that substantially increased the likelihood of TA among patients referred for biopsy were jaw claudication (positive likelihood ratio [LR], 4.2; 95% confidence interval [CI], 2.8-6.2) and diplopia (positive LR, 3.4; 95% CI, 1.3-8.6). The absence of any temporal artery abnormality was the only clinical factor that modestly reduced the likelihood of disease (negative LR, 0.53; 95% CI, 0.38-0.75). Predictive physical findings included temporal artery beading (positive LR, 4.6; 95% CI, 1.1-18.4), prominence (positive LR, 4.3; 95% CI, 2.1-8.9), and tenderness (positive LR, 2.6; 95% CI, 1.9-3.7). Normal ESR values indicated much less likelihood of disease (negative LR for abnormal ESR, 0.2; 95% CI, 0.08-0.51).
CONCLUSIONS: A small number of clinical features are helpful in predicting the likelihood of a positive temporal artery biopsy among patients with a clinical suspicion of disease; the most useful finding is a normal ESR, which makes TA unlikely.
Gabriel SE, O'Fallon WM, Achkar AA, Lie JT, Hunder GG.
The use of clinical characteristics to predict the results of temporal artery biopsy among patients with suspected giant cell arteritis.
J Rheumatol. 1995 Jan;22(1):93-6.
Abstract/Text
OBJECTIVE: To develop a mathematical model which predicts temporal artery biopsy results.
METHODS: We collected clinical and laboratory data as well as biopsy results among a consecutive cohort of all individuals who underwent temporal artery biopsy at Mayo Medical Center between January 1, 1988 and December 31, 1991. All biopsies were independently reviewed by one pathologist. Logistic regression was used to identify a set of variables which best predicted the biopsy results. This model was then used to identify patients who were highly likely (> or = 95% predictive value) to have either a negative or a positive biopsy. A receiver operating characteristic (ROC) curve was generated using the best fit model.
RESULTS: Of the 525 people in the study, there were 187 men and 338 women. The logistic regression model and the ROC curve generated from this model were of modest value in predicting biopsy results from prebiopsy clinical characteristics. However, this model identified 60 (11%) individuals who had a > or = 95% probability of having a negative biopsy. None of these individuals had any symptoms of claudication, only 5 of 60 (8%) had temporal artery abnormalities on examination, 45 (75%) had synovitis (suggesting an alternate diagnosis), and their median erythrocyte sedimentation rate was only 31 mm/h (Westergren).
CONCLUSIONS: In individuals with these findings, we recommend a careful search for other diagnoses before temporal artery biopsy.
Hunder GG, Bloch DA, Michel BA, Stevens MB, Arend WP, Calabrese LH, Edworthy SM, Fauci AS, Leavitt RY, Lie JT.
The American College of Rheumatology 1990 criteria for the classification of giant cell arteritis.
Arthritis Rheum. 1990 Aug;33(8):1122-8. doi: 10.1002/art.1780330810.
Abstract/Text
Criteria for the classification of giant cell (temporal) arteritis were developed by comparing 214 patients who had this disease with 593 patients with other forms of vasculitis. For the traditional format classification, 5 criteria were selected: age greater than or equal to 50 years at disease onset, new onset of localized headache, temporal artery tenderness or decreased temporal artery pulse, elevated erythrocyte sedimentation rate (Westergren) greater than or equal to 50 mm/hour, and biopsy sample including an artery, showing necrotizing arteritis, characterized by a predominance of mononuclear cell infiltrates or a granulomatous process with multinucleated giant cells. The presence of 3 or more of these 5 criteria was associated with a sensitivity of 93.5% and a specificity of 91.2%. A classification tree was also constructed using 6 criteria. These criteria were the same as for the traditional format, except that elevated erythrocyte sedimentation rate was excluded, and 2 other variables were included: scalp tenderness and claudication of the jaw or tongue or on deglutition. The classification tree was associated with a sensitivity of 95.3% and specificity of 90.7%.
Ponte C, Grayson PC, Robson JC, Suppiah R, Gribbons KB, Judge A, Craven A, Khalid S, Hutchings A, Watts RA, Merkel PA, Luqmani RA; DCVAS Study Group.
2022 American College of Rheumatology/EULAR Classification Criteria for Giant Cell Arteritis.
Arthritis Rheumatol. 2022 Dec;74(12):1881-1889. doi: 10.1002/art.42325. Epub 2022 Nov 8.
Abstract/Text
OBJECTIVE: To develop and validate updated classification criteria for giant cell arteritis (GCA).
METHODS: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in 6 phases: 1) identification of candidate items, 2) prospective collection of candidate items present at the time of diagnosis, 3) expert panel review of cases, 4) data-driven reduction of candidate items, 5) derivation of a points-based risk classification score in a development data set, and 6) validation in an independent data set.
RESULTS: The development data set consisted of 518 cases of GCA and 536 comparators. The validation data set consisted of 238 cases of GCA and 213 comparators. Age ≥50 years at diagnosis was an absolute requirement for classification. The final criteria items and weights were as follows: positive temporal artery biopsy or temporal artery halo sign on ultrasound (+5); erythrocyte sedimentation rate ≥50 mm/hour or C-reactive protein ≥10 mg/liter (+3); sudden visual loss (+3); morning stiffness in shoulders or neck, jaw or tongue claudication, new temporal headache, scalp tenderness, temporal artery abnormality on vascular examination, bilateral axillary involvement on imaging, and fluorodeoxyglucose-positron emission tomography activity throughout the aorta (+2 each). A patient could be classified as having GCA with a cumulative score of ≥6 points. When these criteria were tested in the validation data set, the model area under the curve was 0.91 (95% confidence interval [95% CI] 0.88-0.94) with a sensitivity of 87.0% (95% CI 82.0-91.0%) and specificity of 94.8% (95% CI 91.0-97.4%).
CONCLUSION: The 2022 American College of Rheumatology/EULAR GCA classification criteria are now validated for use in clinical research.
© 2022 American College of Rheumatology.
Narváez J, Estrada P, Vidal-Montal P, Nolla JM.
Performance of the new 2022 ACR/EULAR classification criteria for giant cell arteritis in clinical practice in relation to its clinical phenotypes.
Autoimmun Rev. 2023 Oct;22(10):103413. doi: 10.1016/j.autrev.2023.103413. Epub 2023 Aug 19.
Abstract/Text
BACKGROUND: To examine the performance of the new 2022 American College of Rheumatology (ACR)/EULAR classification criteria for giant cell arteritis (GCA) in routine clinical care, compared with the 1990 ACR GCA classification criteria.
METHODS: The fulfilment of 2022 ACR/EULAR and 1990 ACR criteria was tested in our real-life cohort of GCA patients with proven vasculitis by temporal artery biopsy or imaging (a necessary pre-requisite to apply the new criteria is the presence of a confirmed diagnosis of medium- or large-vessel vasculitis). The performance of classification criteria was evaluated in all patients with GCA across different subsets of the disease. Patients with GCA were compared with unselected controls with suspected GCA.
RESULTS: A total of 136 patients with proven GCA were identified. The new criteria had a sensitivity of 92.6% and a specificity of 85.2%. According to the clinical phenotypes, the sensitivity was 98.8% in cranial GCA, 92% in extracranial large vessel (LV) GCA and 75% in occult systemic GCA. These data are much better than those observed with the 1990 ACR classification criteria, which showed a sensitivity of 66.1% and a specificity of 85.1% for the total sample, with a sensitivity of 89.1% in cranial GCA, 24% in extracranial LV-GCA and 35.7% in occult systemic GCA. Ten (7.4%) patients in our cohort did not fulfil either of the criteria sets (8 with occult systemic GCA and 2 with extracranial LV-GCA). The sensitivity of the new criteria in patients with occult systemic and extracranial LV-GCA could be greatly improved assigning more weight (3 points) to some imaging findings (axillary involvement and FDG-PET activity throughout the aorta).
CONCLUSION: Our study confirms that the new classification criteria are more sensitive in real-life settings than the old ACR criteria across all clinical phenotypes.
Copyright © 2023 Elsevier B.V. All rights reserved.
Mackie SL, Dejaco C, Appenzeller S, Camellino D, Duftner C, Gonzalez-Chiappe S, Mahr A, Mukhtyar C, Reynolds G, de Souza AWS, Brouwer E, Bukhari M, Buttgereit F, Byrne D, Cid MC, Cimmino M, Direskeneli H, Gilbert K, Kermani TA, Khan A, Lanyon P, Luqmani R, Mallen C, Mason JC, Matteson EL, Merkel PA, Mollan S, Neill L, Sullivan EO, Sandovici M, Schmidt WA, Watts R, Whitlock M, Yacyshyn E, Ytterberg S, Dasgupta B.
British Society for Rheumatology guideline on diagnosis and treatment of giant cell arteritis.
Rheumatology (Oxford). 2020 Mar 1;59(3):e1-e23. doi: 10.1093/rheumatology/kez672.
Abstract/Text
Dejaco C, Ramiro S, Bond M, Bosch P, Ponte C, Mackie SL, Bley TA, Blockmans D, Brolin S, Bolek EC, Cassie R, Cid MC, Molina-Collada J, Dasgupta B, Nielsen BD, De Miguel E, Direskeneli H, Duftner C, Hočevar A, Molto A, Schäfer VS, Seitz L, Slart RHJA, Schmidt WA.
EULAR recommendations for the use of imaging in large vessel vasculitis in clinical practice: 2023 update.
Ann Rheum Dis. 2024 May 15;83(6):741-751. doi: 10.1136/ard-2023-224543. Epub 2024 May 15.
Abstract/Text
OBJECTIVES: To update the EULAR recommendations for the use of imaging modalities in primary large vessel vasculitis (LVV).
METHODS: A systematic literature review update was performed to retrieve new evidence on ultrasound, MRI, CT and [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) for diagnosis, monitoring and outcome prediction in LVV. The task force consisted of 24 physicians, health professionals and patients from 14 countries. The recommendations were updated based on evidence and expert opinion, iterating until voting indicated consensus. The level of agreement was determined by anonymous votes.
RESULTS: Three overarching principles and eight recommendations were agreed. Compared to the 2018 version, ultrasound is now recommended as first-line imaging test in all patients with suspected giant cell arteritis, and axillary arteries should be included in the standard examination. As an alternative to ultrasound, cranial and extracranial arteries can be examined by FDG-PET or MRI. For Takayasu arteritis, MRI is the preferred imaging modality; FDG-PET, CT or ultrasound are alternatives. Although imaging is not routinely recommended for follow-up, ultrasound, FDG-PET or MRI may be used for assessing vessel abnormalities in LVV patients with suspected relapse, particularly when laboratory markers of inflammation are unreliable. MR-angiography, CT-angiography or ultrasound may be used for long-term monitoring of structural damage, particularly at sites of preceding vascular inflammation.
CONCLUSIONS: The 2023 EULAR recommendations provide up-to-date guidance for the role of imaging in the diagnosis and assessment of patients with LVV.
© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.
Maz M, Chung SA, Abril A, Langford CA, Gorelik M, Guyatt G, Archer AM, Conn DL, Full KA, Grayson PC, Ibarra MF, Imundo LF, Kim S, Merkel PA, Rhee RL, Seo P, Stone JH, Sule S, Sundel RP, Vitobaldi OI, Warner A, Byram K, Dua AB, Husainat N, James KE, Kalot MA, Lin YC, Springer JM, Turgunbaev M, Villa-Forte A, Turner AS, Mustafa RA.
2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Giant Cell Arteritis and Takayasu Arteritis.
Arthritis Rheumatol. 2021 Aug;73(8):1349-1365. doi: 10.1002/art.41774. Epub 2021 Jul 8.
Abstract/Text
OBJECTIVE: To provide evidence-based recommendations and expert guidance for the management of giant cell arteritis (GCA) and Takayasu arteritis (TAK) as exemplars of large vessel vasculitis.
METHODS: Clinical questions regarding diagnostic testing, treatment, and management were developed in the population, intervention, comparator, and outcome (PICO) format for GCA and TAK (27 for GCA, 27 for TAK). Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of the evidence. Recommendations were developed by the Voting Panel, comprising adult and pediatric rheumatologists and patients. Each recommendation required ≥70% consensus among the Voting Panel.
RESULTS: We present 22 recommendations and 2 ungraded position statements for GCA, and 20 recommendations and 1 ungraded position statement for TAK. These recommendations and statements address clinical questions relating to the use of diagnostic testing, including imaging, treatments, and surgical interventions in GCA and TAK. Recommendations for GCA include support for the use of glucocorticoid-sparing immunosuppressive agents and the use of imaging to identify large vessel involvement. Recommendations for TAK include the use of nonglucocorticoid immunosuppressive agents with glucocorticoids as initial therapy. There were only 2 strong recommendations; the remaining recommendations were conditional due to the low quality of evidence available for most PICO questions.
CONCLUSION: These recommendations provide guidance regarding the evaluation and management of patients with GCA and TAK, including diagnostic strategies, use of pharmacologic agents, and surgical interventions.
© 2021 American College of Rheumatology. This article has been contributed to by US Government employees and their work is in the public domain in the USA.
González-Gay MA, García-Porrúa C, Llorca J, Hajeer AH, Brañas F, Dababneh A, González-Louzao C, Rodriguez-Gil E, Rodríguez-Ledo P, Ollier WE.
Visual manifestations of giant cell arteritis. Trends and clinical spectrum in 161 patients.
Medicine (Baltimore). 2000 Sep;79(5):283-92. doi: 10.1097/00005792-200009000-00001.
Abstract/Text
Giant cell (temporal) arteritis (GCA) is the most common systemic vasculitis in Western countries. It involves large and medium-sized vessels with predisposition to the cranial arteries in the elderly. Cranial ischemic complications, in particular permanent visual loss, constitute the most feared aspects of this vasculitis. Although the use of corticosteroids and a higher physician awareness may have contributed to a decrease in the frequency of severe ischemic complications, permanent visual loss is still present in 7%-14% of patients. To investigate further the incidence, trends, and clinical spectrum of visual manifestations in patients with GCA, we examined the features of patients with biopsy-proven GCA diagnosed at the single reference hospital for a defined population in northwestern Spain during an 18-year period. Predictive factors for the development of any visual manifestation, not only permanent visual loss, were also examined. Between 1981 and 1998, 161 patients were diagnosed with biopsy-proven GCA. Visual ischemic complications were observed in 42 (26.1%), and irreversible blindness, mainly due to anterior ischemic optic neuropathy and frequently preceded by amaurosis fugax, was found in 24 (14.9%). Despite a progressive increase in the number of new cases diagnosed, there was not a significant change in the proportion of patients with visual manifestations during the study period (p = 0.37). Patients with visual ischemic complications had lower clinical and laboratory biologic markers of inflammation. Indeed, during the last years of the study, anemia was associated with a very low risk of visual complications. Also, HLA-DRB1*04-positive patients had visual manifestations more commonly. Patients with other ischemic complications developed irreversible blindness more frequently. The best predictors of any visual complication were HLA-DRB1*04 phenotype (odds ratio [OR] 7.47) and the absence of anemia at the time of admission (OR for patients with anemia = 0.07). The best predictors of irreversible blindness (permanent visual loss) were amaurosis fugax (OR 12.63) and cerebrovascular accidents (OR 26.51). The present study supports the claim that ocular ischemic complications are still frequent in biopsy-proven GCA patients from southern Europe. The presence of other ischemic complications constitutes an alarm for the development of irreversible blindness. In contrast, a higher inflammatory response may be a protective factor against the development of cranial ischemic events.
Salvarani C, Cimino L, Macchioni P, Consonni D, Cantini F, Bajocchi G, Pipitone N, Catanoso MG, Boiardi L.
Risk factors for visual loss in an Italian population-based cohort of patients with giant cell arteritis.
Arthritis Rheum. 2005 Apr 15;53(2):293-7. doi: 10.1002/art.21075.
Abstract/Text
OBJECTIVE: To evaluate the frequency of visual manifestations at presentation in an Italian population-based cohort of patients with biopsy-proven giant cell arteritis (GCA), and to investigate predictors for the development of permanent visual loss.
METHODS: We identified 136 Reggio Emilia (Italy) residents with biopsy-proven GCA diagnosed between 1986 and 2002. Medical records of these 136 patients were reviewed, and demographic, clinical, and laboratory data were collected.Multivariate analysis with multiple logistic regression models was performed to identify the best predictors of visual loss.
RESULTS: Visual manifestations developed in 41 patients (30.1%). Partial or total visual loss was observed in 26 patients (19.1%). Anterior ischemic optic neuropathy was seen in 24 patients, and 2 patients had central retinal artery occlusion. Unilateral vision loss occurred in 19 patients, and bilateral visual loss in 7. In 25 patients, visual loss developed before glucocorticoid therapy for GCA was started. The age at disease onset was significantly higher in patients with permanent visual loss compared with those without it. The frequency of systemic signs/symptoms and erythrocyte sedimentation rate (ESR) and C-reactive protein values at diagnosis were significantly lower in patients with permanent visual loss. By multivariate logistic regression, the only statistically significant predictor for the development of permanent visual loss was the absence of high levels of ESR at diagnosis (tertile 2: Odds ratio [OR] 0.08; tertile 3: OR 0.11). Other predictors included in the model were the absence of systemic manifestations (OR 0.24), an older age at disease diagnosis (quintile 5: OR 5.60), and the presence of an elevated platelet count at diagnosis (OR 4.99), however they were only of borderline statistical significance.
CONCLUSION: The proportion of Italian patients with GCA that developed visual loss was similar to that reported from other countries. The patients with low inflammatory response had a higher risk of visual loss.
Chen JJ, Leavitt JA, Fang C, Crowson CS, Matteson EL, Warrington KJ.
Evaluating the Incidence of Arteritic Ischemic Optic Neuropathy and Other Causes of Vision Loss from Giant Cell Arteritis.
Ophthalmology. 2016 Sep;123(9):1999-2003. doi: 10.1016/j.ophtha.2016.05.008. Epub 2016 Jun 11.
Abstract/Text
PURPOSE: To determine the incidence of permanent visual loss from giant cell arteritis (GCA).
DESIGN: Retrospective, population-based cohort.
PARTICIPANTS: All residents of Olmsted County, Minnesota, diagnosed with GCA between January 1, 1950, and December 31, 2009.
METHODS: All cases of GCA were identified using the Rochester Epidemiology Project (REP), which is a record-linkage system of medical records for all patient-physician encounters among Olmsted County, Minnesota, residents. The medical records were reviewed to identify and determine the cause of permanent vision loss among patients with GCA. Systemic symptoms of GCA and visual outcomes also were determined.
MAIN OUTCOME MEASURES: Incidence and outcomes of permanent vision loss from GCA.
RESULTS: Among the 245 new cases of GCA over the 60-year period, 20 patients (8.2%) had permanent vision loss due to GCA. The frequency of arteritic ischemic optic neuropathy (A-ION) was 6.9% (95% confidence interval [CI], 4.0-11.1) accounting for 85% of cases of permanent vision loss. The frequency of central retinal artery occlusion (CRAO) was 1.6% (95% CI, 0.4-4.2), and the frequency of cilioretinal artery occlusion was 0.4% (95% CI, 0.01-2.3). The population-based age- and sex-adjusted annual incidence of A-ION from GCA among persons aged ≥50 years was 1.3 (95% CI, 0.7-2.0) per 100 000 population. Some 20% of patients with permanent vision loss from GCA had vision loss without constitutional symptoms of GCA. Overall, there was no significant difference between presenting and final visual acuities.
CONCLUSIONS: These population-based data provide the most accurate incidence of permanent vision loss from GCA. This study confirms that visual outcomes from GCA-related vision loss are poor and that 20% of patients with permanent visual loss from GCA can present without systemic symptoms of GCA.
Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
Maleszewski JJ, Younge BR, Fritzlen JT, Hunder GG, Goronzy JJ, Warrington KJ, Weyand CM.
Clinical and pathological evolution of giant cell arteritis: a prospective study of follow-up temporal artery biopsies in 40 treated patients.
Mod Pathol. 2017 Jun;30(6):788-796. doi: 10.1038/modpathol.2017.10. Epub 2017 Mar 3.
Abstract/Text
Although clinical signs and symptoms of giant cell arteritis improve promptly after starting glucocorticoid therapy, reports have suggested that the vascular inflammation may persist. To assess the duration and quality of histopathologic changes in treated patients, we prospectively obtained second temporal artery biopsies in patients treated for 3 to 12 months after their first diagnostic biopsy. Forty patients (28 women, 12 men, median age 77 years) agreed to have a second temporal artery biopsy randomly assigned to 3, 6, 9, or 12 months subsequent to the first. Clinical and laboratory evaluation of the patient cohort revealed a typical rapid response and continued suppression of clinical manifestations as a result of glucocorticoid treatment. Histopathologic findings, evaluated in a blinded manner by a cardiovascular pathologist, showed unequivocal findings of vasculitis in 7/10 patients with second temporal artery biopsy at 3 months, 9/12 at 6 months, 4/9 at 9 months, and 4/9 at 12 months. Lymphocytes were present in all positive initial biopsies and remained the dominant cell population in chronically treated patients. Granulomatous inflammation decreased in a time-dependent manner from 78 to 100% at initial biopsy to 50% at 9 months and 25% at 12 months. The increased medial fibrosis noted in the second biopsies (60 vs 33% in primary temporal artery biopsies) suggested that the finding may represent a chronic finding in arteritis. In summary, the response to glucocorticoids in giant cell arteritis was frequently discordant. Clinical manifestations were readily suppressed, but vascular changes were gradual and often incomplete.
Achkar AA, Lie JT, Hunder GG, O'Fallon WM, Gabriel SE.
How does previous corticosteroid treatment affect the biopsy findings in giant cell (temporal) arteritis?
Ann Intern Med. 1994 Jun 15;120(12):987-92. doi: 10.7326/0003-4819-120-12-199406150-00003.
Abstract/Text
OBJECTIVE: To determine the effect of previous corticosteroid treatment on the results of temporal artery biopsy.
DESIGN: Consecutive case series.
SETTING: Tertiary care center.
PATIENTS: A consecutive cohort of 535 patients who had temporal artery biopsies at Mayo Clinic, Rochester, Minnesota, between 1 January 1988 and 31 December 1991.
MEASUREMENTS AND RESULTS: The dose and duration of corticosteroid treatment received before temporal artery biopsy and detailed clinical and laboratory data were obtained from the patients' medical records. All temporal artery biopsy slides were re-evaluated by a pathologist blinded to clinical data, previous corticosteroid treatment information, and the original pathologic diagnosis. Biopsy specimens were classified as negative for arteritis, positive for typical temporal arteritis, or positive for atypical temporal arteritis. Biopsy results were positive for 31% of patients (89 of 286) who did not receive corticosteroids before biopsy and for 35% of those (86 of 249) who did receive corticosteroids before biopsy (P = 0.4; 95% confidence interval for the difference, -4.7% to 11.5%). Patients who received corticosteroids before biopsy tended to have clinical features more suggestive of arteritis. A multiple logistic regression analysis model, controlling for these differences in clinical and laboratory features, showed that the biopsy positivity rate was unrelated to previous corticosteroid treatment.
CONCLUSIONS: Although these results do not prove that histologic features are unaffected by corticosteroids, they show that, in this large, consecutive sample, the positivity rates of temporal artery biopsy were similar in untreated and corticosteroid-treated patients. Temporal artery biopsy may show arteritis even after more than 14 days of corticosteroid therapy in the presence of clinical indications of active disease.
Jakobsson K, Jacobsson L, Mohammad AJ, Nilsson JÅ, Warrington K, Matteson EL, Turesson C.
The effect of clinical features and glucocorticoids on biopsy findings in giant cell arteritis.
BMC Musculoskelet Disord. 2016 Aug 24;17(1):363. doi: 10.1186/s12891-016-1225-2. Epub 2016 Aug 24.
Abstract/Text
BACKGROUND: To investigate the effect of baseline clinical characteristics and glucocorticoid treatment on temporal artery biopsy (TAB) findings in patients with giant cell arteritis (GCA).
METHODS: Individuals who developed GCA after inclusion in two population-based health surveys were identified through linkage to the local and the national patient registers. In addition, other patients diagnosed with GCA at the Departments of Internal Medicine and Rheumatology at an area hospital were included. A structured review of medical records and TAB pathology reports was performed. The presence or absence of giant cells, granuloma, fragmented internal elastic lamina, fibrosis and grade of inflammatory infiltrates were recorded.
RESULTS: In 183 cases with a confirmed clinical diagnosis of GCA, 139 were biopsied after start of glucocorticoids (median treatment duration 3 days; interquartile range 2-5). Patients with a positive TAB (77 %) had significantly higher C-reactive protein (CRP; p = 0.007) and erythrocyte sedimentation rate (ESR; p = 0.03) at the time of clinical diagnosis. A positive TAB tended to more common in women, but there was no difference in the proportion of patients with polymyalgia rheumatica or visual symptoms. Patients biopsied before or on the same day as initial treatment where more likely than those biopsied 1-3 days after treatment start to have positive biopsy [odds ratio (OR) 2.86; 95 % CI 1.06-7.70] as well as inflammatory infiltrates (OR 3.30; 95 % CI 1.15-9.49). There was no significant difference in the proportions of a fragmented internal lamina (p = 0.86), giant cells (p = 0.10), granuloma (p = 0.19), minor inflammatory infiltrates (p = 0.47), major inflammatory infiltrates (p = 0.09), or overall positive biopsy (p = 0.17) report by treatment duration comparing: ≤ 0 days, 1-3 days, 4-6 days, 7-28 days. Among those biopsied 7-28 days after start of treatment, 80 % of TABs were positive, and histopathology features were not substantially different from those biopsied after shorter glucocorticoid treatment.
CONCLUSION: Biopsies were more likely to be positive and have characteristic histopathologic features in patients with high CRP and ESR, and prior to start of corticosteroid treatment TABs taken 1-4 weeks after initiation of glucocorticoid treatment reveal changes consistent with GCA and therefore still yields clinically useful information for the diagnosis.
Narváez J, Bernad B, Roig-Vilaseca D, García-Gómez C, Gómez-Vaquero C, Juanola X, Rodriguez-Moreno J, Nolla JM, Valverde J.
Influence of previous corticosteroid therapy on temporal artery biopsy yield in giant cell arteritis.
Semin Arthritis Rheum. 2007 Aug;37(1):13-9. doi: 10.1016/j.semarthrit.2006.12.005. Epub 2007 Mar 23.
Abstract/Text
OBJECTIVE: To determine the impact of prior corticosteroid treatment on temporal artery biopsy (TAB) yield to establish the diagnosis of giant cell arteritis (GCA).
METHODS: Retrospective study of a consecutive cohort of 78 patients clinically diagnosed and managed as GCA, who received corticosteroids before TAB.
RESULTS: Among the 78 patients, TAB was positive in 57 (73%) and negative in 21 (27%). No significant differences in the length of the specimen were found between the positive and negative biopsies. We grouped patients according to treatment duration before TAB. In those with newly diagnosed GCA treated with high-dose steroid therapy, the biopsy results were positive in 78% (35/45) of patients treated for less than 2 weeks, in 65% of those treated for 2 to 4 weeks (13/20), and in 40% of those treated for more than 4 weeks (2/5). We also observed 8 patients that developed GCA on a background of a prior history of polymyalgia rheumatica (PMR); in this group biopsy was positive in 88% of the cases, after a median duration of treatment of 180 +/- 172 days and an average daily dose of 7.1 +/- 1.4 mg/d.
CONCLUSION: The performance of TAB should not delay the prompt institution of steroid therapy on diagnosis of GCA, since the diagnostic yield of TAB seems valuable within 4 weeks of starting high-dose steroid treatment. In patients that developed GCA on a background of a prior history of PMR, a late TAB is also generally informative despite long-term treatment with low doses of corticosteroids.
Proven A, Gabriel SE, Orces C, O'Fallon WM, Hunder GG.
Glucocorticoid therapy in giant cell arteritis: duration and adverse outcomes.
Arthritis Rheum. 2003 Oct 15;49(5):703-8. doi: 10.1002/art.11388.
Abstract/Text
OBJECTIVE: To evaluate the course of glucocorticoid (GC) therapy and associated adverse events in a population-based cohort of patients with giant cell arteritis (GCA).
METHODS: We identified 125 Olmsted County residents with GCA diagnosed between 1950 and 1991 and obtained followup information on the 120 patients who were diagnosed antemortem and agreed to participate in this study. Clinical variables, GC doses, and GC adverse events on each patient were recorded. The relationship between GC therapy and the development of adverse events was studied by the Cox and Anderson-Gill proportional hazards models.
RESULTS: All patients were treated with GCs and responded rapidly (median initial dosage 60 mg prednisone/day). The dosage was later reduced according to the treating physicians' judgment. The median duration required to reach 7.5 mg/day was 6.5 months and the median duration required to reach 5 mg/day was 7.5 months. Relapses or recurrences occurred in 57 patients. For the 87 patients followed to discontinuation of GC therapy and permanent remission of GCA (median of 22 months), the total median dose of prednisone was 6.47 gm. Adverse events associated with GCs were recorded in 103 (86%) patients and 2 or more events occurred in 70 patients (58%). Age and higher cumulative dose of GCs were associated with the development of adverse GC side effects.
CONCLUSION: GCs are therapeutically effective in GCA and the prednisone dosage was reduced to physiologic levels in three-fourths of the patients within 1 year. However, most patients developed serious adverse side effects related to GCs, indicating that less toxic therapeutic measures are needed.
Stone JH, Tuckwell K, Dimonaco S, Klearman M, Aringer M, Blockmans D, Brouwer E, Cid MC, Dasgupta B, Rech J, Salvarani C, Schett G, Schulze-Koops H, Spiera R, Unizony SH, Collinson N.
Trial of Tocilizumab in Giant-Cell Arteritis.
N Engl J Med. 2017 Jul 27;377(4):317-328. doi: 10.1056/NEJMoa1613849.
Abstract/Text
BACKGROUND: Giant-cell arteritis commonly relapses when glucocorticoids are tapered, and the prolonged use of glucocorticoids is associated with side effects. The effect of the interleukin-6 receptor alpha inhibitor tocilizumab on the rates of relapse during glucocorticoid tapering was studied in patients with giant-cell arteritis.
METHODS: In this 1-year trial, we randomly assigned 251 patients, in a 2:1:1:1 ratio, to receive subcutaneous tocilizumab (at a dose of 162 mg) weekly or every other week, combined with a 26-week prednisone taper, or placebo combined with a prednisone taper over a period of either 26 weeks or 52 weeks. The primary outcome was the rate of sustained glucocorticoid-free remission at week 52 in each tocilizumab group as compared with the rate in the placebo group that underwent the 26-week prednisone taper. The key secondary outcome was the rate of remission in each tocilizumab group as compared with the placebo group that underwent the 52-week prednisone taper. Dosing of prednisone and safety were also assessed.
RESULTS: Sustained remission at week 52 occurred in 56% of the patients treated with tocilizumab weekly and in 53% of those treated with tocilizumab every other week, as compared with 14% of those in the placebo group that underwent the 26-week prednisone taper and 18% of those in the placebo group that underwent the 52-week prednisone taper (P<0.001 for the comparisons of either active treatment with placebo). The cumulative median prednisone dose over the 52-week period was 1862 mg in each tocilizumab group, as compared with 3296 mg in the placebo group that underwent the 26-week taper (P<0.001 for both comparisons) and 3818 mg in the placebo group that underwent the 52-week taper (P<0.001 for both comparisons). Serious adverse events occurred in 15% of the patients in the group that received tocilizumab weekly, 14% of those in the group that received tocilizumab every other week, 22% of those in the placebo group that underwent the 26-week taper, and 25% of those in the placebo group that underwent the 52-week taper. Anterior ischemic optic neuropathy developed in one patient in the group that received tocilizumab every other week.
CONCLUSIONS: Tocilizumab, received weekly or every other week, combined with a 26-week prednisone taper was superior to either 26-week or 52-week prednisone tapering plus placebo with regard to sustained glucocorticoid-free remission in patients with giant-cell arteritis. Longer follow-up is necessary to determine the durability of remission and safety of tocilizumab. (Funded by F. Hoffmann-La Roche; ClinicalTrials.gov number, NCT01791153 .).
Stone JH, Han J, Aringer M, Blockmans D, Brouwer E, Cid MC, Dasgupta B, Rech J, Salvarani C, Spiera R, Unizony SH, Bao M; GiACTA investigators.
Long-term effect of tocilizumab in patients with giant cell arteritis: open-label extension phase of the Giant Cell Arteritis Actemra (GiACTA) trial.
Lancet Rheumatol. 2021 May;3(5):e328-e336. doi: 10.1016/S2665-9913(21)00038-2. Epub 2021 Mar 19.
Abstract/Text
BACKGROUND: The combination of tocilizumab plus a glucocorticoid taper is effective in maintaining clinical remission without requiring additional glucocorticoid therapy in patients with giant cell arteritis, as shown in part one of the Giant Cell Arteritis Actemra (GiACTA) trial. However, the duration of the tocilizumab effect after discontinuation is unknown. Here, we explored the maintenance of efficacy 1 year after discontinuation of tocilizumab treatment, the effectiveness of retreatment with tocilizumab after relapse, and the long-term glucocorticoid-sparing effect of tocilizumab.
METHODS: In part one of the GiACTA trial, 251 patients were randomly assigned (2:1:1:1) to receive subcutaneous tocilizumab (162 mg) once a week or every other week, combined with a 26-week prednisone taper, or placebo combined with a prednisone taper over a period of either 26 weeks or 52 weeks. Patients in clinical remission stopped masked injections at 1 year (the conclusion of part one). In part two, treatment was at the investigators' discretion and could consist of no treatment, tocilizumab, glucocorticoids, methotrexate, or combinations of these, for two years. Maintenance of efficacy as assessed by clinical remission (defined as absence of relapse determined by the investigator), cumulative glucocorticoid dose, and long-term safety were exploratory objectives in part two of the trial. This trial is registered at ClinicalTrials.gov, NCT01791153.
FINDINGS: 215 patients participated in part two of the trial; 81 patients who were randomly assigned to tocilizumab once a week in part one were in clinical remission after 1 year, of whom 59 started part two on no treatment. 25 of these 59 patients (42%) maintained tocilizumab-free and glucocorticoid-free clinical remission throughout part two. Median (95% CI) cumulative glucocorticoid doses over 3 years were 2647 mg (1987-3507) for tocilizumab once a week, 3948 mg (2352-5186) for tocilizumab-every-other-week, 5277 mg (3944-6685) for placebo with a 26-week prednisone taper, and 5323 mg (3900-6951) for placebo with a 52-week prednisone taper (van Elteren p≤0·001, tocilizumab once a week vs placebo groups; p<0·05, tocilizumab-every-other-week vs placebo groups). Tocilizumab-based regimens restored clinical remission among patients who experienced relapse in part two and were treated (median time to remission: 15 days for tocilizumab alone [n=17]; 16 days for tocilizumab plus glucocorticoids [n=36]; and 54 days for glucocorticoids alone [n=27]). No new or unexpected safety findings were reported over the full 3 years of the study.
INTERPRETATION: Giant cell arteritis remains a chronic disease that entails ongoing management and careful vigilance for disease relapse, but continuous indefinite treatment with immunosuppressive drugs is not required for all patients. A substantial proportion of patients treated with tocilizumab for one year maintain drug-free remission during the two years after tocilizumab cessation. For patients who experience relapse, tocilizumab can be used to manage relapses, but it remains prudent to include prednisone for patients who experience relapse because of the risk for vision loss.
FUNDING: F Hoffmann-La Roche.
Copyright © 2021 Elsevier Ltd. All rights reserved.
Stone JH, Spotswood H, Unizony SH, Aringer M, Blockmans D, Brouwer E, Cid MC, Dasgupta B, Rech J, Salvarani C, Spiera R, Bao M.
New-onset versus relapsing giant cell arteritis treated with tocilizumab: 3-year results from a randomized controlled trial and extension.
Rheumatology (Oxford). 2022 Jul 6;61(7):2915-2922. doi: 10.1093/rheumatology/keab780.
Abstract/Text
OBJECTIVE: Tocilizumab plus prednisone induces sustained glucocorticoid-free remission in patients with GCA. However, its long-term benefits in new-onset vs relapsing disease are uncertain, and the value of weekly vs every-other-week dosing has not been evaluated.
METHODS: In Giant-Cell Arteritis Actemra (GiACTA) part 1, patients with new-onset or relapsing GCA received blinded tocilizumab weekly (TCZ QW), tocilizumab every-other-week (TCZ Q2W) or placebo for 52 weeks, with a prednisone taper. In part 2 (open-label), patients were treated at investigator discretion for 104 weeks. In this analysis, patients were evaluated according to their original treatment assignments, and outcomes beyond 52 weeks were assessed. Outcomes of interest included time to first flare and cumulative glucocorticoid exposure over 3 years according to baseline disease status.
RESULTS: Part 1 enrolled 250 patients; 215 entered part 2. At baseline, 48% had new-onset disease and 52% had relapsing disease. In patients with new-onset and relapsing disease, the median time to first flare in the TCZ QW group was 577 and 575 days, respectively, vs 479 and 428 days with TCZ Q2W and 179 and 224 days with placebo; the median cumulative glucocorticoid dose was 3068 mg and 2191 mg with TCZ QW, 4080 mg and 2353 mg with TCZ Q2W, and 4639 mg and 6178 mg with placebo.
CONCLUSION: TCZ QW delayed the time to flare and reduced the cumulative glucocorticoid dose in patients with relapsing GCA and new-onset GCA. These data support initiating TCZ QW as part of first-line therapy in all patients with active GCA.
TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT01791153.
© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.
Hoffman GS, Cid MC, Hellmann DB, Guillevin L, Stone JH, Schousboe J, Cohen P, Calabrese LH, Dickler H, Merkel PA, Fortin P, Flynn JA, Locker GA, Easley KA, Schned E, Hunder GG, Sneller MC, Tuggle C, Swanson H, Hernández-Rodríguez J, Lopez-Soto A, Bork D, Hoffman DB, Kalunian K, Klashman D, Wilke WS, Scheetz RJ, Mandell BF, Fessler BJ, Kosmorsky G, Prayson R, Luqmani RA, Nuki G, McRorie E, Sherrer Y, Baca S, Walsh B, Ferland D, Soubrier M, Choi HK, Gross W, Segal AM, Ludivico C, Puechal X; International Network for the Study of Systemic Vasculitides.
A multicenter, randomized, double-blind, placebo-controlled trial of adjuvant methotrexate treatment for giant cell arteritis.
Arthritis Rheum. 2002 May;46(5):1309-18. doi: 10.1002/art.10262.
Abstract/Text
OBJECTIVE: To evaluate treatment with methotrexate (MTX) in patients with newly diagnosed giant cell arteritis (GCA) to determine if MTX reduces GCA relapses and cumulative corticosteroid (CS) requirements and diminishes disease- and treatment-related morbidity.
METHODS: This was a multicenter, randomized, double-blind study. Over 4 years, 16 centers from the International Network for the Study of Systemic Vasculitides enrolled patients with unequivocal GCA. The initial treatment was 1 mg/kg/day (RESULTS: Ninety-eight patients were enrolled. No significant differences between treatment groups were noted with regard to age, frequency of positive findings on temporal artery biopsy (placebo 87%, MTX 79%), or comorbidities at the time of enrollment. The median dosage of MTX was 15 mg/week. The incidence of treatment failure was comparable between groups after 12 months: 57.5% in the MTX group failed treatment (95% confidence interval [95% CI] 41.6-73.4%) compared with 77.3% in the placebo group (95% CI 61.9-92.8%) (P = 0.26). In a Cox regression analysis, MTX was not associated with a reduced risk of treatment failure (relative risk 0.72; 95% CI 0.41-1.28). There were no significant differences between groups with regard to abnormal elevations of the erythrocyte sedimentation rate following initial remissions, serious morbidity due to GCA, cumulative CS dose, or treatment toxicity. In the MTX group, there were fewer cases of GCA relapse heralded by symptoms of isolated polymyalgia rheumatica (1 case versus 5 in the placebo group; P = 0.05).
CONCLUSION: The results of this randomized, multicenter trial do not support the adjunctive use of MTX to control disease activity or to decrease the cumulative dose and toxicity of CS in patients with GCA.
Jover JA, Hernández-García C, Morado IC, Vargas E, Bañares A, Fernández-Gutiérrez B.
Combined treatment of giant-cell arteritis with methotrexate and prednisone. a randomized, double-blind, placebo-controlled trial.
Ann Intern Med. 2001 Jan 16;134(2):106-14. doi: 10.7326/0003-4819-134-2-200101160-00010.
Abstract/Text
BACKGROUND: Corticosteroids remain the cornerstone of therapy for giant-cell arteritis, but relapse during dose tapering and corticosteroid-related adverse events often complicate management of this condition. Although several approaches, including combined therapy with cytotoxic agents, have been suggested to overcome these problems, no study has clearly shown benefits of alternate treatments.
OBJECTIVE: To analyze the safety and efficacy of combined therapy with corticosteroids and methotrexate in giant-cell arteritis.
DESIGN: Randomized, double-blind, placebo-controlled trial.
SETTING: University-based clinic.
PATIENTS: 42 patients with new-onset giant-cell arteritis according to biopsy.
INTERVENTION: High initial doses of corticosteroid were given; the dose was then tapered quickly until therapy was completely withdrawn. Methotrexate or placebo was given weekly from the start of corticosteroid therapy for 24 months.
MEASUREMENTS: Number of relapses, cumulative dose of corticosteroid, and number of adverse events were assessed on completion of follow-up.
RESULTS: Compared with combined prednisone and placebo therapy, treatment with prednisone and methotrexate reduced the proportion of patients who experienced at least one relapse (45% vs. 84.2%; P = 0.02) and the proportion of patients who experienced multiple relapses (P = 0.004). The mean cumulative dose of prednisone was 4187 +/- 1529 mg in the methotrexate group and 5489.5 +/- 1396 mg in the placebo group (mean difference, 1302 mg [95% CI, 350 to 2253 mg]; P = 0.009). Overall, the rate and severity of adverse events were similar between groups. Treatment was discontinued in 3 patients in the methotrexate group who experienced definite drug-related adverse events. In sensitivity analysis that included patients lost to follow-up, differences between groups in number of relapses and cumulative dose of prednisone were significant.
CONCLUSIONS: Treatment with methotrexate plus corticosteroid is a safe alternative to corticosteroid therapy alone in patients with giant-cell arteritis and is more effective in controlling disease.
Langford CA, Cuthbertson D, Ytterberg SR, Khalidi N, Monach PA, Carette S, Seo P, Moreland LW, Weisman M, Koening CL, Sreih AG, Spiera R, McAlear CA, Warrington KJ, Pagnoux C, McKinnon K, Forbess LJ, Hoffman GS, Borchin R, Krischer JP, Merkel PA; Vasculitis Clinical Research Consortium.
A Randomized, Double-Blind Trial of Abatacept (CTLA-4Ig) for the Treatment of Giant Cell Arteritis.
Arthritis Rheumatol. 2017 Apr;69(4):837-845. doi: 10.1002/art.40044. Epub 2017 Mar 3.
Abstract/Text
OBJECTIVE: To compare the efficacy of abatacept to that of placebo for the treatment of giant cell arteritis (GCA).
METHODS: In this multicenter trial, patients with newly diagnosed or relapsing GCA were treated with abatacept 10 mg/kg intravenously on days 1, 15, and 29 and week 8, together with prednisone administered daily. At week 12, patients in remission underwent a double-blinded randomization to continue to receive abatacept monthly or switch to placebo. Patients in both study arms received a standardized prednisone taper, with discontinuation of prednisone at week 28. All patients remained on their randomized assignment until meeting criteria for early termination or until 12 months after enrollment of the last patient. The primary end point was duration of remission (relapse-free survival rate).
RESULTS: Forty-nine eligible patients with GCA were enrolled and treated with prednisone and abatacept; of these, 41 reached the week 12 randomization and underwent a blinded randomization to receive abatacept or placebo. Prednisone was tapered using a standardized schedule, reaching a daily dosage of 20 mg at week 12 with discontinuation in all patients at week 28. The relapse-free survival rate at 12 months was 48% for those receiving abatacept and 31% for those receiving placebo (P = 0.049). A longer median duration of remission was seen in those receiving abatacept compared to those receiving placebo (median duration 9.9 months versus 3.9 months; P = 0.023). There was no difference in the frequency or severity of adverse events, including infection, between the treatment arms.
CONCLUSION: In patients with GCA, the addition of abatacept to a treatment regimen with prednisone reduced the risk of relapse and was not associated with a higher rate of toxicity compared to prednisone alone.
© 2017, American College of Rheumatology.
