Assessment of the Efficacy and Safety of Tocilizumab in Patients Over 80 Years old With Giant Cell Arteritis

Hubert de Boysson; Maelle Le Besnerais; Félix Blaison; Aurélie Daumas; Pierre-André Jarrot; François Perrin; Nathalie Tieulié; Alexandre Maria; Pierre Duffau; Bruno Gombert; Maxime Samson; Olivier Espitia; Marc Lambert; Arsène Mékinian; Achille Aouba

Disclosures

Arthritis Res Ther. 2021;23(143)

Patients and Methods

Patients

In January 2019, physicians belonging to the French Study Group for Large Vessel Vasculitis (GEFA) were asked to include in a register their patients who received TCZ for the treatment of GCA for at least 2 months. GCA diagnosis was retained if the patient satisfied at least 3 criteria from the American College of Rheumatology, showed a positive temporal artery biopsy (TAB), or demonstrated large-vessel vasculitis on imaging. A standardized electronic form was sent to each physician who declared a patient. Anonymized data were thus collected in a centralized database.

In December 2020, 186 patients were included in the register, including 21 (11%) patients over 80 years old.

The Caen Ethical Board approved the study (CLERS ID265).

Data Collection and Definition

The data collection included demographics, cardiovascular risk factors (hypertension, hypercholesterolemia, diabetes mellitus, tobacco use), GCA-related cranial symptoms (headaches, scalp tenderness, jaw claudication, temporal artery abnormality, visual signs), polymyalgia rheumatica (PMR), limb claudication, fever, weight loss, acute phase reactants (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP]), the results of histology (TAB or another vascular sample if available), the results of imaging, treatment regimens, and outcomes.

Regarding GC management, we retrieved the date of introduction, initial dose, dose at TCZ initiation and discontinuation, and duration of treatment. When GC tapering was not possible under a certain dose because of relapses, we qualified the disease as GC-dependent.

Regarding TCZ management, we noted the delay of introduction after GCs, duration of treatment, and route used (intravenous [IV] or subcutaneous [SC]). The indication for TCZ was noted among the four possible nonexclusive following criteria: GC-sparing effect, relapsing disease, severe GCA involvement (the severity of GCA was left to the physician's judgment), and failure of a previous immunosuppressant other than GCs.

Regarding TCZ tolerance, the following side effects were screened: infections, forms of cytopenia, hepatic or digestive toxicity, dyslipidemia requiring a specific medical treatment, or allergy. The Common Toxicity Criteria for Adverse Events (CTCAE) was used to grade the adverse events (scaling from 1 to 5), with the 5th grade corresponding to death.^[8]

Statistical Analysis

Categorical variables are expressed as numbers (%), and quantitative variables are expressed as medians [range].

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Table 1. Baseline characteristics of patients with giant-cell arteritis over 80 years old who received tocilizumab
Characteristics	Patients (n = 21)
Demographics
Age	84 [81–90]
Female sex	16 (76)
Past medical history
Number of cardiovascular risk factors (except age and sex)	1 [0–3]
Hypertension	11 (52)
Tobacco use	2 (10)
Diabetes mellitus	4 (19)
Hypercholesterolemia	6 (29)
Overweight	2 (10)
Coronary disease	4 (19)
Previous stroke	2 (10)
Diverticulosis	2 (10)
Osteoporotic fractures	2 (10)
Myelodysplasia	1 (5)
Clinical manifestations
ACR criteria	4 [3–5]
Weight loss	15 (71)
Fever	5 (24)
Headaches	17 (81)
Jaw claudication	12 (57)
Abnormal temporal artery	7 (33)
Scalp tenderness	7 (33)
Ophthalmologic involvement	7 (33)
Polymyalgia rheumatica	9 (43)
Limb claudication	1 (5)
Laboratory parameters
Erythrocyte sedimentation rate, in mm	82 [25–138]
C-reactive protein, in mg/l	90 [16–224]
Hemoglobin level, g/dl	10.3 [9.2–15.1]
Positive histology	11/16 (69)
Large-vessel vasculitis ^a	7/16 (44)
At GCA diagnosis	4/13 (31)
During follow-up	3/3 (100)

Values are numbers (%) or medians [range]. CV, cardiovascular; ACR, American College of Rheumatology; GCA, giant-cell arteritis
^aIn patients who underwent large-vessel imaging

Table 2. Treatment and outcomes of patients with giant-cell arteritis over 80 years old who received tocilizumab
Characteristics	Patients (n = 21)
Total follow-up, in months	20 [3–48]
Antiplatelets	18 (86)
Glucocorticoid use
Initial dose, mg/kg	0.8 [0.6–1.1]
Duration of intake in all patients ^a, in months	14 [2–48]
Number of patients who stopped GCs after TCZ introduction	14 (67)
Delay to stop GCs after TCZ introduction	8 [2–21]
Tocilizumab use
Introduction at GCA diagnosis	6 (29)
Introduction during the FU	15 (71)
Delay of introduction in patients with TCZ introduction at FU	8 [3–37]
First-line immunosuppressant	17 (81)
Second-line immunosuppressant	4 (19)
Number of patients who discontinued TCZ at last FU	11 (52)
Duration of TCZ use in all patients, in months	7 [3–28]
Duration of TCZ in patients who stopped it, in months	8 [3–28]
Number of patients with a control of large-vessel imaging	3
Improvement	2
No improvement	1
Relapses before and after TCZ introduction
Number of patients who relapsed	11 (52)
Total number of relapses	19
Delay of the first relapse, in months	5 [2–19]
Number of relapses before TCZ	15
Under TCZ	2
After TCZ discontinuation	2
Delay of relapse after TCZ discontinuation, in months	1 and 13
Death	4 (19)

Values are numbers (%) or medians [range]. GCs, glucocorticoids; FU, follow-up; TCZ, tocilizumab
^aFrom GC introduction to stop or to the last follow-up visit if GCs are ongoing

Table 3. Adverse events and outcomes observed in patients once TCZ started for GCA
Adverse event	Months after TCZ introduction	Dose of GC at AE time	GC duration (months)	CTCAE grade	Treatment/evolution
Patient 1
Hypercholesterolemia	4	10 mg	4	2	No treatment, stable
Patient 2
Hypercholesterolemia	8	10 mg	8	3	Statin, improvement
Patient 3
Hypercholesterolemia	3	0	–	2	No treatment, stable
Patient 4
Pyelonephritis	5	10 mg	9	3	IV antibiotics-TCZ shifted 1 month later
Thrombopenia	2	15 mg	6	1 (75 G/l)	No treatment, stable
Patient 5
Bronchitis	9	6 mg	13	2	Oral antibiotics, healed
Neutropenia	7	8 mg	11	3 (900/mm³)	No treatment, stable
Hepatic cytolysis	7	8 mg	11	3 (5N)	Reduction TCZ to 4 mg/kg, correction of cytolysis
Patient 6
Septic shock^a	20	0	–	5	Death
Mesenteric infarction^a	20	0	–	5
Patient 7
Hypercholesterolemia	9	0	–	2	No treatment, stable

Values are numbers (%). TCZ, tocilizumab; AE, adverse events; IV, intravenous; G, giga; N, normal; GC, glucocorticoid; CTCAE, Common Toxicity Criteria for Adverse Events
^aOccurred post-surgery for a programmed cholecystectomy. TCZ was temporally stopped for 2 months