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In the GiACTA trial,1 tocilizumab (TCZ) combined with prednisone (PDN) was significantly superior to PDN alone to obtain the remission in patients with giant cell arteritis (GCA) with and without concomitant large vessel vasculitis (LVV). To date, no data on the management of patients achieving the remission with TCZ monotherapy after a short course of combined treatment with CS are available.
To investigate the persistence of remission after TCZ interruption, we designed an open-label, prospective trial of 15 consecutive patients meeting the American College of Rheumatology 1990 criteria for GCA.2 Four patients had refractory GCA and 11 were new diagnoses (clinical and demographic data: see online supplementary table S1). All had concomitant thoracic LVV evidenced by 18-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT. Total vascular score (TVS), maximal standardised uptake value (SUVmax) and target to background ratio (TBR) were calculated.3 PET/CT was performed at baseline, month 6 and 2 months after TCZ withdrawn. As shown in table 1, at baseline all received PDN 50 mg/day and intravenous TCZ (ivTCZ) at the dose of 8 mg/kg/monthly or subcutaneous TCZ (scTCZ) at the dose of 162 mg/weekly. PDN was rapidly tapered with interruption at month 2.
Primary outcome measure: the percentage of patients maintaining the clinical remission over the 6month off-therapy period. Remission was defined by the absence of GCA symptoms and signs, thoracic complaints, values of erythrocyte sedimentation rate (ESR) ≤15 mm/hour; C-reactive protein (CRP) ≤0.5 mg/dL; pain visual analogue scale (VAS) ≤10. Secondary outcome measures: the percentage of patients achieving and maintaining the clinical remission during the treatment with TCZ, and the role of acute-phase reactants and 18F-FDG-PET as predictors of remission. A written informed consent was obtained by all patients. Clinical Trials.gov Identifier: NCT03244709.
Baseline values ( mean ± SD ): ESR 63.8±22.7, CRP 6.34±4.63 mg/dL, VAS 8.65±0.91 cm, SUVmax 5,25±0.66, TVS 12.2±4.41 and TBR 2.13±0.44. All 15 patients achieved and maintained the remission, and in 10 (66.7%) the condition persisted at month 18 (table 1). Five patients reactivated after 2–4 months from treatment interruption. Retreatment with TCZ at the last dose allowed to achieve the remission in all, and in two of them still persisted over a follow-up of 8 and 14 months from the second TCZ withdrawal. The remaining three patients remained symptom-free under TCZ treatment at the lowest dose. None required CS to regain the remission and all received a cumulative PDN dose of 1225 mg. At month 14, ESR, CRP and VAS improved significantly in all patients, while SUVmax, TBR and TVS resulted significantly reduced only in the 10 patients maintaining the off-therapy remission. In non-responders, a significant correlation between SUVmax and TBR was detected (Pearson 0.97: p=0.004 and 0.98: p=0.003), but not with ESR, CRP, and VAS. At month 14, SUVmax (p<0.001), TBR (p<0.001) and TVS (p<0.034) were significantly higher in non-responders.
TCZ therapy was well tolerated with no severe adverse events (only two urinary infections). Hypercholesterolaemia requiring statins occurred in two patients.
The open-label design and the low number of patients limit the strength of the results of this study. Nevertheless, the drug-free remission maintenance after TCZ discontinuation seems to be possible in GCA. The scheduled therapy, with rapid PDN withdrawal and progressive TCZ taper allowed a consistent CS sparing with respect to recent reports.1 4 5 According to other studies,6 PET/CT confirmed a relevant role in the management of patients with GCA. Finally, our therapeutic schedule may represent a good option in GCA patients with comorbidities such as diabetes, hypertension, osteoporosis, and glaucoma.
Handling editor Prof Josef S Smolen
Contributors FC, CN and LN equally contributed to the study design projecting, patients’ recruitment and management, statistical analysis and manuscript writing. SS, IL and AC performed and evaluated the PET/CT results and reviewed the manuscript. All revised and corrected the manuscript.
Competing interests No, there are no competing interests for any author.
Patient consent for publication Not required.
Ethics approval The study was approved by the local ethical committee.
Provenance and peer review Not commissioned; externally peer reviewed.
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