Giant Cell Arteritis Hoffman, Gary S
Annals of internal medicine,
2016-Nov-01, Letnik:
165, Številka:
9
Journal Article
Recenzirano
This issue provides a clinical overview of giant cell arteritis, focusing on diagnosis, treatment, and practice improvement. The content of In the Clinic is drawn from the clinical information and ...education resources of the American College of Physicians (ACP), including MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of additional science writers and physician writers.
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.
PURPOSE OF REVIEWTo critically review recent advances in medical management of Takayasu arteritis, with a special focus on the rationale and evidence to support the use of biologic agents in this ...disease.
RECENT FINDINGSMultiple case series and observational studies support the use of anti-tumor necrosis factor (TNF) medications, in particular infliximab, in patients who relapse upon tapering steroids and/or adding nonbiologic immunosuppressive agents. However, these medications must be continued to maintain effect, and often patients require increased doses over time. Tocilizumab and rituximab have been shown to lead to improved disease activity in small numbers of Takayasuʼs patients, including those refractory to anti-TNF treatment.
SUMMARYAnti-TNF agents are recommended for the treatment of Takayasuʼs patients who are unable to taper prednisone despite treatment with a nonbiologic immunosuppressive medication. Whether these biologic agents should be considered earlier in the treatment algorithm of these complicated patients remains an area of interest. Tocilizumab and rituximab may also be of benefit in refractory patients. Prospective randomized controlled trials are needed to confirm these findings.
This study of ANCA-associated vasculitis compared a single course of rituximab with conventional immunosuppression with cyclophosphamide followed by azathioprine and showed similar results for the ...primary outcome of complete remission by 6 months, maintained through 18 months.
Granulomatosis with polyangiitis (previously termed Wegener's granulomatosis) and microscopic polyangiitis are called antineutrophil cytoplasmic antibody (ANCA)–associated vasculitides because they are frequently accompanied by autoantibodies against proteinase 3 or myeloperoxidase.
1
,
2
For nearly four decades, cyclophosphamide and glucocorticoids have been the standard therapy for the induction of remission. However, the primary results of the Rituximab in ANCA-Associated Vasculitis (RAVE) trial
3
and results from a European trial
4
showed that rituximab was as effective as cyclophosphamide for the induction of remission in patients with severe disease. Moreover, the rituximab-based regimen was superior in patients who had relapsing disease at 6 months.
3
Rituximab has . . .
Objective
To identify and validate, using computer‐driven methods, patterns of arterial disease in Takayasu arteritis (TAK) and giant cell arteritis (GCA).
Methods
Patients with TAK or GCA were ...studied from the Diagnostic and Classification Criteria for Vasculitis (DCVAS) cohort and a combined North American cohort. Case inclusion required evidence of large‐vessel involvement, defined as stenosis, occlusion, or aneurysm by angiography/ultrasonography, or increased 18F‐fluorodeoxyglucose (FDG) uptake by positron emission tomography (PET) in at least 1 of 11 specified arterial territories. K‐means cluster analysis identified groups of patients based on the pattern of arterial involvement. Cluster groups were identified in the DCVAS cohort and independently validated in the North American cohort.
Results
A total of 1,068 patients were included (DCVAS cohort: TAK = 461, GCA = 217; North American cohort: TAK = 225, GCA = 165). Six distinct clusters of patients were identified in DCVAS and validated in the North American cohort. Patients with TAK were more likely to have disease in the abdominal vasculature, bilateral disease of the subclavian and carotid arteries, or focal disease limited to the left subclavian artery than GCA (P < 0.01). Patients with GCA were more likely to have diffuse disease, involvement of bilateral axillary/subclavian arteries, or minimal disease without a definable pattern than TAK (P < 0.01). Patients with TAK were more likely to have damage by angiography, and patients with GCA were more likely to have arterial FDG uptake by PET without associated vascular damage.
Conclusion
Arterial patterns of disease highlight both shared and divergent vascular patterns between TAK and GCA and should be incorporated into classification criteria for large‐vessel vasculitis.
This multicenter, randomized, double-blind, double-dummy, noninferiority trial compared rituximab with cyclophosphamide for remission induction in ANCA−associated vasculitis. Rituximab therapy was ...not inferior to daily cyclophosphamide treatment for remission induction in severe ANCA-associated vasculitis and may be superior in relapsing disease.
Rituximab therapy was not inferior to daily cyclophosphamide treatment for remission induction in severe ANCA-associated vasculitis and may be superior in relapsing disease.
Wegener's granulomatosis and microscopic polyangiitis are classified as antineutrophil cytoplasmic antibody (ANCA)−associated vasculitides because most patients with generalized disease have antibodies against proteinase 3 or myeloperoxidase.
1
,
2
The ANCA-associated vasculitides affect small-to-medium-size blood vessels, with a predilection for the respiratory tract and kidneys.
3
–
6
Cyclophosphamide and glucocorticoids have been the standard therapy for remission induction for nearly four decades.
7
,
8
This regimen transformed the usual treatment outcome of severe ANCA-associated vasculitis from death to a strong likelihood of disease control and temporary remission.
3
–
5
,
9
_
11
However, not all patients have a remission with this combination of drugs, and those . . .
Objective
To compare the efficacy of abatacept to that of placebo for the treatment of Takayasu arteritis (TAK).
Methods
In this multicenter trial, patients with newly diagnosed or relapsing TAK 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, reaching a dosage of 20 mg daily at week 12, 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).
Results
Thirty‐four eligible patients with TAK were enrolled and treated with prednisone and abatacept; of these, 26 reached the week 12 randomization and underwent a blinded randomization to receive either abatacept or placebo. The relapse‐free survival rate at 12 months was 22% for those receiving abatacept and 40% for those receiving placebo (P = 0.853). Treatment with abatacept in patients with TAK enrolled in this study was not associated with a longer median duration of remission (median duration 5.5 months for abatacept versus 5.7 months for placebo). There was no difference in the frequency or severity of adverse events, including infection, between the treatment arms.
Conclusion
In patients with TAK, the addition of abatacept to a treatment regimen with prednisone did not reduce the risk of relapse.
Objective
Relapse following remission is common in antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV), particularly with ANCAs directed at proteinase 3 (PR3). This study was ...undertaken to evaluate the association of an increase in PR3‐ANCA level with subsequent relapse.
Methods
Data from the Rituximab versus Cyclophosphamide for ANCA‐Associated Vasculitis (RAVE) trial were used. Starting from the time of achieving complete remission, serial measurements by direct and capture enzyme‐linked immunosorbent assays (ELISAs) were analyzed in 93 patients with PR3‐ANCA, using Cox proportional hazards regression.
Results
An increase in PR3‐ANCA level was identified in 58 of 93 subjects (62.4%) by direct ELISA and in 59 of 93 (63.4%) by capture ELISA. Relapses occurred in 55 of 93 subjects (59.1%), with 25 and 21 occurring within 1 year after an increase by direct ELISA and capture ELISA, respectively. An increase by direct ELISA was associated with subsequent severe relapses (hazard ratio HR 4.57; P < 0.001), particularly in patients presenting with renal involvement (HR 7.94; P < 0.001) and alveolar hemorrhage (HR 24.19; P < 0.001). Both assays identified increased risk for severe relapse in the rituximab group (HR 5.80; P = 0.002 for direct ELISA and HR 4.54; P = 0.007 for capture ELISA) but not the cyclophosphamide/azathioprine group (P = 0.103 and P = 0.197, respectively).
Conclusion
The association of an increase in PR3‐ANCA level with the risk of subsequent relapse is partially affected by the PR3‐ANCA detection methodology, disease phenotype, and remission induction treatment. An increase in PR3‐ANCA level during complete remission conveys an increased risk of relapse, particularly severe relapse, among patients with renal involvement or alveolar hemorrhage and those treated with rituximab. Serial measurements of PR3‐ANCA may be informative in this subset of patients, but the risk of relapse must be weighed carefully against the risks associated with therapy.
To compare patterns of arteriographic lesions of the aorta and primary branches in patients with Takayasu's arteritis (TAK) and giant cell arteritis (GCA).
Patients were selected from two North ...American cohorts of TAK and GCA. The frequency of arteriographic lesions was calculated for 15 large arteries. Cluster analysis was used to derive patterns of arterial disease in TAK versus GCA and in patients categorised by age at disease onset. Using latent class analysis, computer derived classification models based upon patterns of arterial disease were compared with traditional classification.
Arteriographic lesions were identified in 145 patients with TAK and 62 patients with GCA. Cluster analysis demonstrated that arterial involvement was contiguous in the aorta and usually symmetric in paired branch vessels for TAK and GCA. There was significantly more left carotid (p=0.03) and mesenteric (p=0.02) artery disease in TAK and more left and right axillary (p<0.01) artery disease in GCA. Subclavian disease clustered asymmetrically in TAK and in patients ≤55 years at disease onset and clustered symmetrically in GCA and patients >55 years at disease onset. Computer derived classification models distinguished TAK from GCA in two subgroups, defining 26% and 18% of the study sample; however, 56% of patients were classified into a subgroup that did not strongly differentiate between TAK and GCA.
Strong similarities and subtle differences in the distribution of arterial disease were observed between TAK and GCA. These findings suggest that TAK and GCA may exist on a spectrum within the same disease.
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