The characteristics of the 21 patients are shown in Table 1. Nine (43%) patients were ≥85 years old at diagnosis, and 76% of the included patients were women. Among the patients, one had myelodysplasia with refractory anemia, and two were known to have colonic diverticulosis. The treatments administered to the patients are indicated in Table 2. GCs were introduced at 0.8 [0.6–1.1] mg/kg/day. The intravenous method was used to administer TCZ to 14 patients, and the subcutaneous method was used for the other 7.
In 6 (29%) patients, TCZ was introduced with GCs (median initial dose 60 [30–70] mg/day) at GCA diagnosis to obtain a fast GC-sparing effect in 4 (metabolic and cardiovascular indication in 2, psychiatric indication in 2) or because of GCA-related severity in 2 (bilateral acute anterior ischemic optic neuropathy (AION) in one, large-vessel vasculitis of the 4 limbs in another). In these 6 patients, after a median follow-up of 12 [4–31] months, GC doses were tapered to 0 [0–10] mg/day, including four patients who discontinued GCs 2 to 8 months after initiation and did not relapse thereafter. Two patients had stopped TCZ after 3 months of use and did not relapse. None of these 6 patients experienced any cardiovascular event or psychiatric decompensation after treatment introduction. The patient with bilateral AION maintained important visual sequelae, and the other with peripheral large-vessel vasculitis showed improvement in clinical and imaging parameters. Only one of the 6 patients exhibited clinical relapse (headaches and polymyalgia rheumatica) in the 8th month under GC and TCZ therapy. An increase in GC dosage controlled the disease.
In the 15 (71%) remaining patients, TCZ was introduced at a median delay of 8 [3–37] months after GC initiation for the nonexclusive following reasons: GC-sparing effect in 10; relapsing disease in 8; disease severity in 2, including large-vessel vasculitis affecting the carotids with a stroke in one, relapse with AION in the last; and/or failure of a previous immunosuppressant line in 4, including methotrexate in 3 and anakinra in 1. The nonexclusive GC-related toxicities in the 10 patients in whom a sparing effect was required were neuropsychiatric deterioration in 7, amyotrophy and loss of autonomy in 4, diabetes instability in 2, symptomatic arterial hypertension in 1, and severe glaucoma in 1. The median GC dose at TCZ introduction was 20 [5–60] mg/day, which was decreased after a median of 10 [3–36] months to 0 [0–25] mg/day. Ten of the 15 patients were able to discontinue GCs after 8 [4–21] months, including 6 who were GC-dependent before TCZ. Moreover, 9/15 had stopped TCZ after a median duration of 10 [4–33] months. Altogether, 3/15 patients relapsed once TCZ was introduced. One relapse occurred during TCZ treatment with a resumption of headaches and polymyalgia rheumatica signs. The other two corresponded to clinical and biological resumption of GCA signs 1 and 13 months after TCZ discontinuation. Both patients were retreated with TCZ and exhibited new clinical remission.
Four (19%) patients in the whole cohort died after 18 [4–47] months: 2 from cardiovascular events (multiple strokes in the first, mesenteric infarction in the other); another from renal cancer while under GC and TCZ; and the last following mechanic fall complications. GCA was not directly responsible for death in these four patients.
Safety information regarding TCZ is indicated in Table 3. A total of 7 (33%) patients experienced 11 adverse events, the most common being hypercholesterolemia observed in 4 patients. Serious adverse events with ≥ grade 3 toxicities were observed in 4 (19%) patients. Intravenous administration was used in 5/7 patients. Three patients experienced infections, including 2 who were receiving concomitant GCs. Patient 6 died from septic shock and a mesenteric infarction occurring 2 days after a programmed cholecystectomy. GCs were stopped for 1 year, and TCZ infusions were temporally suspended for the 2 months prior to the surgery. No patient with diverticulosis showed complications, nor did the patient with myelodysplasia. Two cytopenias were noted: thrombopenia at 75 giga/l and neutropenia at 900/mm3. Finally, a 5-fold increase in transaminase levels was observed in a patient and improved with a reduction in TCZ dose from 8 to 4 mg/kg, without any GCA relapse.
Arthritis Res Ther. 2021;23(143) © 2021 BioMed Central, Ltd.
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