Tocilizumab Therapy in Giant Cell Arteritis: Insights from Clinical Experience

Ricardo Blanco; Javier Loricera

doi:10.37871/jbres2174

ISSN: 2766-2276

2025 August 30;6(8):1164-1167. doi: 10.37871/jbres2174.

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Clinical Trials

Tocilizumab Therapy in Giant Cell Arteritis: Insights from Clinical Experience

Ricardo Blanco^1,2* and Javier Loricera^1,2

¹Department of Rheumatology, Hospital Universitario Marqués de Valdecilla, Santander, Spain
²Immunopathology Group, Instituto de Investigación Valdecilla (IDIVAL), Santander, Spain

*Corresponding authors: Ricardo Blanco, Rheumatology Division, IDIVAL, Hospital Universitario Marqués de Valdecilla, Avenida Valdecilla s/n, 39008, Santander, Spain E-mail:

Received: 15 August 2025 | Accepted: 29 August 2025 | Published: 30 August 2025

How to cite this article: Blanco R, Loricera J. Tocilizumab Therapy in Giant Cell Arteritis: Insights from Clinical Experience. J Biomed Res Environ Sci. 2025 Aug 30; 6(8): 1163-1167. doi: 10.37871/jbres2174, Article ID: jbres1757

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Clinical Trials

Giant Cell Arteritis (GCA) is the most frequent form of vasculitis in Europe and North America, primarily affecting individuals over the age of 50, with a higher incidence among those of Northern European ancestry [1-3].

Currently, three GCA phenotypes can be distinguished based on the vessels affected: cranial GCA (cGCA), when the cranial vessels are involved; extracranial GCA (ecGCA), when the aorta or its main branches are affected in the absence of cranial artery involvement; and mixed GCA (mixGCA), when both cranial and extracranial vessels are affected [4]. Feared complications of cGCA include irreversible vision loss, while ecGCA is associated with aortitis, aneurysm formation, and risk of dissection [5-7].

Although the definitive etiopathogenesis remains unknown, vascular inflammation is driven by T helper 1 (Th1) and T helper 17 (Th17) cells, along with macrophage-derived cytokines such as interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-alpha (TNF-α). IL-6, a key inflammatory cytokine, is elevated in the serum of GCA patients and plays a pivotal role in the immunopathogenesis of the condition [8].

Tocilizumab (TCZ), a humanized monoclonal antibody targeting the IL-6 receptor, has demonstrated efficacy via Intravenous (IV) and Subcutaneous (SC) administration [9,10]. The GiACTA trial confirmed the efficacy of TCZ in inducing remission, preventing relapses, and reducing Glucocorticoid (GC) dependence [10]. Although the GiACTA study led to the approval of TCZ for GCA by the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA), important questions remain unresolved: the optimal duration of treatment, the best strategy for tapering or discontinuation, its precise role in cranial and extracranial phenotypes, and its impact on visual complications. Moreover, real-world data on adverse effects in clinical practice are still limited and warrant further investigation. Several studies from clinical practice have also demonstrated effectiveness of TCZ in GCA [4,7,11-14].

We studied the largest series of GCA patients from clinical practice treated with TCZ. The series consisted of 471 patients. TCZ shows rapid and sustained effectiveness in all GCA phenotypes in achieving clinical remission and EULAR-defined complete remission. By contrast, absence of inflammation on imaging studies was much lower in ecGCA and mixGCA [4]. Moreover, in our series there were 196 patients with GCA-aortitis treated with TCZ. After 6 months, 72.2% (101 out of 144 patients with available data) reached clinical and analytical remission, but only 12% (3 out of 25 patients with available data) achieved imaging remission; increasing up to 81.4% (95 out of 128 patients with available data) and 31.8% (12 out of 55 patients with available data), respectively, at 24 months [7]. This highlights the dissociation between clinical remission and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scan improvement in TCZ-treated patients with large-vessel GCA, which has also been demonstrated in other studies [15].

Additionally, aneurysms were present in 10 patients. Five of them required early surgery, while three others enlarged. No patient on TCZ therapy developed new aneurysms during follow-up. This suggests that TCZ may prevent the development of new aneurysms in patients with GCA, but it does not appear to prevent the progression of pre-existing aneurysms [7].

Regarding visual manifestations, in our series of 471 patients, none of those with prior transient visual loss experienced new episodes following the initiation of TCZ. Among the 60 patients with permanent visual loss, only 11 showed any improvement, and in most cases, this was partial. These findings suggest that TCZ may exert a protective effect against the onset of new visual complications or recurrent transient visual symptoms in GCA. However, once permanent visual damage is established, the likelihood of significant recovery appears limited [11]. Similarly, in a series of 60 GCA patients treated with TCZ, Unizony S, et al. [12] observed that TCZ reduced the incidence of new visual manifestations, and no flares associated with permanent visual loss occurred while patients were receiving TCZ. Notwithstanding, one patient in the GiACTA study who was receiving TCZ at a dose of 162 mg SC every other week developed Anterior Ischemic Optic Neuropathy (AION) at week 24, while the patient was on concomitant prednisone at a dose of 2 mg/day [16]. In this regard, one of the patients in the GUSTO trial developed AION 15 days after GC pulse therapy, while the patient was treated with TCZ as monotherapy without GC [17]. For this reason, we believe that in the presence of visual symptoms, TCZ should be administered at a dose of 162 mg SC weekly and initially combined with high doses of GCs.

An interesting aspect is the possible benefit of combining TCZ with conventional immunosuppressive drugs (cISD), such as Methotrexate (MTX). In a series of 134 patients with refractory GCA in which 52 (38.8%) patients received TCZ in combination with cISD, Calderón-Goercke, et al. [18] observed that the improvement was similar between patients receiving TCZ in monotherapy and those using it in combination with cISD at 12 months, although in the patients who received TCZ in combination, prolonged remission was significantly higher at 12 months. Relapses and serious adverse events were similar in both groups. It should be noted that in the group of patients who received TCZ in combination, there was a higher proportion of patients with large-vessel involvement (57% vs. 34.1%, p = 0.007) [18]. In a subsequent study, we evaluated the effectiveness of TCZ in combination with cISD compared to TCZ in monotherapy in the 196 patients with GCA-aortitis, observing that although there were no differences in clinical and analytical remission, imaging remission was higher with TCZ in combination (50% vs. 15.8%, p = 0.026) after 24 months from TCZ initiation [19]. In addition, the prednisone-sparing effect was higher in patients receiving combination therapy. In other words, in GCA patients with extracranial involvement, it seems advisable to add MTX to TCZ to achieve greater control of the disease.

Although TCZ is only approved for subcutaneous administration in GCA, it can also be administered intravenously. We conducted a comparative study between both forms of administration in our series of 471 patients, and there were no significant differences in sustained remission or in the GC-sparing effect of TCZ [20].

The optimal duration of TCZ therapy in GCA is unknown. The GiACTA trial showed that after one year of weekly TCZ, most patients (95%) reached sustained remission and TCZ was stopped. Nevertheless, in the extension phase of this study, only 25 out of 59 (42%) patients who started this phase without treatment maintained their treatment-free remission for another two years [21]. Therefore, abruptly discontinuing TCZ does not seem to be a good option.

We assessed whether the progressive optimization of TCZ in GCA patients after reaching prolonged remission is an effective and safe therapeutic option in our series. We evaluated 231 GCA patients on TCZ in prolonged remission [13]. Treatment optimization was carried out in 125 of them. The first TCZ optimization was performed after a median Interquartile Range [IQR] follow-up of 12 [6-17] months. Intravenous TCZ was optimized from 8 to 4 mg/kg every four weeks in 26 of 59 (44%) patients, and subcutaneous TCZ was optimized from 162 mg/week to 162 mg every other week in 43 of 66 (65%) cases. At the end of the follow-up period, prolonged remission rates (78.2% vs. 84.2%, p = 0.29) and relapse rates (5.6% vs. 10.4%, p = 0.18) were similar between optimized and non-optimized patients, with fewer adverse events and improved cost-effectiveness [13]. These findings support the potential optimization of TCZ once remission is achieved.

The relapse rate in GCA during follow-up is variable, patients treated only with GC have high rates of relapse, up to 45 %. In our series, after a mean follow-up of 25.3 ± 21.7 months, relapses were observed in 63 out of 407 (15.5%) patients with available data, all of them non-severe [22]. In multivariate logistic regression analysis, the set of variables associated with GCA relapses were the use of IV TCZ (OR 2.327 [1.244-4.353]), the use of cISD prior to TCZ (OR 5.062 [2.402-10.665]), the optimization of TCZ (OR 2.803 [1.507-5.215]) and TCZ initiation >6 weeks after GCA diagnosis (OR 3.446 [1.196-9931]).

An important aspect is safety, particularly the risk of serious infections in this older population exposed to high doses of GC. In our series, real-life patients treated with TCZ were older, had longer disease duration, higher Erythrocyte Sedimentation Rate (ESR) levels, and had received MTX more commonly than those included in the GiACTA trial. Despite clinical differences, TCZ was equally effective in both GiACTA trial and clinical practice patients [14]. However, serious infections were more commonly observed in GCA patients treated in routine clinical settings. In our cohort, serious infections were observed in 13.4% of patients (n = 63), with an incidence of 6.4 per 100 patient-years [4]. In other diseases, such as rheumatoid arthritis, the incidence of serious infections in clinical practice has been reported as 4.7 per 100 patient-years [24]. This higher rate in our series likely reflects the advanced age and cumulative GC exposure at the time of TCZ initiation in GCA compared with RA.

These results emphasize the potential of TCZ across all domains of GCA with a relatively favorable safety profile. Nonetheless, the occurrence of relapses in some patients-especially when the drug is discontinued-demonstrates that TCZ is not a definitive cure for the disease.