Pneumatosis Intestinalis Developed in a Patient with Giant Cell Arteritis While in a Clinically Sustained Remission Phase

Overview. The GiACTA trial is a multicenter, randomized, double-blind, and placebo-controlled study designed to test the ability of tocilizumab (TCZ), an interleukin (IL)-6 receptor antagonist, to maintain disease remission in patients with giant cell arteritis (GCA).Design. Approximately 100 centers will enroll 250 patients with active disease. The trial consists of a 52-week blinded treatment phase followed by 104 weeks of open-label extension. Patients will be randomized into one of four groups. Group A (TCZ 162 mg weekly plus a 6-month prednisone-taper); group B (TCZ 162 mg every other week plus a 6-month prednisone-taper); group C (placebo plus a 6-month prednisone-taper); and group D (placebo plus a 12-month prednisone taper). We hypothesize that patients assigned to TCZ in addition to a 6-month prednisone course are more likely to achieve the primary efficacy endpoint of sustained remission (SR) at 52 weeks compared with those assigned to a 6-month prednisone course alone, thus potentially minimizing the long-term adverse effects of corticosteroids.Conclusion. GiACTA will test the hypothesis that interference with IL-6 signaling exerts a beneficial effect on patients with GCA. The objective of this paper is to describe the design of the trial and address major issues related to its development.

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Rapid visual recovery following intravenous tocilizumab in glucocorticoid resistant refractory giant cell arteritis

BMJ Case Reports ◽

10.1136/bcr-2019-229236 ◽

2019 ◽

Vol 12 (10) ◽

pp. e229236 ◽

Cited By ~ 1

Author(s):

Carl Richard Svasti-Salee ◽

Susan P Mollan ◽

Ann W Morgan ◽

Vanessa Quick

Keyword(s):

Giant Cell Arteritis ◽

Giant Cell ◽

Vision Loss ◽

Rescue Therapy ◽

Temporal Artery ◽

High Dose ◽

Temporal Artery Biopsy ◽

Sustained Remission ◽

Temporal Arteries ◽

Multiple Pulses

A 72-year-old man presented with a short history of headache, jaw claudication, double vision, amaurosis fugax and distended temporal arteries. A diagnosis of giant cell arteritis (GCA) was confirmed on temporal artery ultrasound and temporal artery biopsy. Despite treatment with high-dose oral glucocorticoid (GC) and multiple pulses of intravenous methylprednisolone, his vision deteriorated to hand movements in one eye. 8 mg/kg intravenous tocilizumab, a humanised, recombinant anti-IL-6 receptor antibody, was administered within 48 hours of vision loss and continued monthly, resulting in marked visual improvement within days, as well as sustained remission of GCA. This case suggests a possible role for tocilizumab as a rescue therapy to prevent or recover visual loss in patients with GCA resistant to GC treatment, termed refractory GCA. Further research is required to elucidate the role of intravenous administration of tocilizumab in this setting.

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Sustained Remission: An Unmet Need in Patients with Giant-cell Arteritis

The Journal of Rheumatology ◽

10.3899/jrheum.150534 ◽

2015 ◽

Vol 42 (7) ◽

pp. 1081-1082 ◽

Cited By ~ 1

Author(s):

MARIA C. CID ◽

MARCO A. ALBA

Keyword(s):

Giant Cell Arteritis ◽

Giant Cell ◽

Unmet Need ◽

Sustained Remission

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Efficacy and safety of secukinumab in patients with giant cell arteritis: study protocol for a randomized, parallel group, double-blind, placebo-controlled phase II trial

Trials ◽

10.1186/s13063-021-05520-1 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Nils Venhoff ◽

Wolfgang A. Schmidt ◽

Peter Lamprecht ◽

Hans-Peter Tony ◽

Christine App ◽

...

Keyword(s):

Giant Cell Arteritis ◽

Giant Cell ◽

Phase Ii ◽

Therapeutic Option ◽

Pathological Finding ◽

Sustained Remission ◽

Efficacy And Safety ◽

Double Blind ◽

Double Blind Placebo ◽

Parallel Group

Abstract Background One key pathological finding in giant cell arteritis (GCA) is the presence of interferon-gamma and interleukin (IL)-17 producing T helper (Th) 1 and Th17 cells in affected arteries. There is anecdotal evidence of successful induction and maintenance of remission with the monoclonal anti-IL-17A antibody secukinumab. Inhibition of IL-17A could therefore represent a potential new therapeutic option for the treatment of GCA. Methods This is a randomized, parallel-group, double-blind, placebo-controlled, multi-center, phase II study in which patients, treating physicians, and the associated clinical staff as well as the sponsor clinical team are blinded. It is designed to evaluate efficacy and safety of secukinumab compared to placebo in combination with an open-label prednisolone taper regimen. Patients included are naïve to biological therapy and have newly diagnosed or relapsing GCA. Fifty patients are randomly assigned in a 1:1 ratio to receive either 300 mg secukinumab or placebo subcutaneously at baseline, weeks 1, 2 and 3, and every 4 weeks from week 4. Patients in both treatment arms receive a 26-week prednisolone taper regimen. The study consists of a maximum 6-week screening period, a 52-week treatment period (including the 26-week tapering), and an 8-week safety follow-up, with primary and secondary endpoint assessments at week 28. Patients who do not achieve remission by week 12 experience a flare after remission or cannot adhere to the prednisolone tapering will enter the escape arm and receive prednisolone at a dose determined by the investigator’s clinical judgment. The blinded treatment is continued. Two optional imaging sub-studies are included (ultrasound and contrast-media enhanced magnetic resonance angiography [MRA]) to assess vessel wall inflammation and occlusion before and after treatment. The primary endpoint is the proportion of patients in sustained remission until week 28 in the secukinumab group compared to the proportion of patients in the placebo group. A Bayesian approach is applied. Discussion The trial design allows the first placebo-controlled data collection on the efficacy and safety of secukinumab in patients with GCA. Trial registration ClinicalTrials.gov NCT03765788. Registration on 5 December 2018, prospective registration, EudraCT number 2018-002610-12; clinical trial protocol number CAIN457ADE11C.

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THU0295 LOW IMMUNOGENICITY IN PATIENTS WITH GIANT CELL ARTERITIS TREATED WITH TOCILIZUMAB: 3-YEAR RESULTS FROM THE RANDOMIZED CONTROLLED PORTION AND OPEN-LABEL FOLLOW-UP OF A PHASE 3 TRIAL

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.2328 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 375.1-376

Author(s):

M. Bao ◽

N. L. Mallalieu ◽

J. H. Stone

Keyword(s):

Giant Cell Arteritis ◽

Giant Cell ◽

Sustained Remission ◽

Open Label ◽

Screening Assay ◽

Randomized Controlled ◽

Long Term Follow Up ◽

Neutralizing Potential

Background:Tocilizumab (TCZ) has low immunogenicity in patients with rheumatoid arthritis.1The risk for immunogenicity remains to be determined in patients with giant cell arteritis (GCA) treated with TCZ. TCZ administered subcutaneously every week (QW) or every other week (Q2W) with 26-week prednisone tapering was superior to placebo (PBO) plus 26-week (PBO+26) or 52-week (PBO+52) prednisone tapering for the achievement of sustained remission in patients with GCA in the 52-week, double-blind part 1 of the GiACTA trial.2Part 2 was a 2-year open-label, long-term follow-up in which patients were treated at the investigators’ discretion; part 2 treatment could include initiation/termination of TCZ QW with or without glucocorticoids or methotrexate.Objectives:To investigate immunogenicity of TCZ QW and Q2W regimens in patients with GCA in combination with a 26-week prednisone taper regimen versus PBO+26 or PBO+52 over the course of the GiACTA study in the randomized controlled part 1 and long-term follow-up part 2.Methods:In parts 1 and 2 combined, anti–TCZ antibodies (ADA) and corresponding pharmacokinetic (PK) parameters were assessed in serum samples taken at scheduled times at weeks 0, 8, 24, 36, 52, 76, 100, 136, and 156 or at early withdrawal. Additional assessments were made for patients who interrupted blinded TCZ treatment for ≥4 weeks in part 1 and those who withdrew from the study because of anaphylaxis/hypersensitivity. All samples were tested by screening assay, and samples that were ADA positive were further analyzed by a confirmation assay to verify specificity. If the confirmation assay was positive, 2 additional tests were performed to characterize the detected ADA: a neutralizing assay to test the neutralizing potential of ADAs and an assay to determine whether the detected ADA were of the IgE isotype. Proportions of patients in whom ADA developed were summarized for the safety population.Results:Among evaluable patients (had baseline and ≥1 postbaseline ADA assessments and received ≥1 dose of study treatment) in part 1, ADA developed in 1 of 95 (1.1%) and 3 of 46 (6.5%) patients after TCZ QW and Q2W dosing, respectively. One of 49 (2.0%) and 1 of 47 (2.1%) in the PBO+26 and PBO+52 groups, respectively, tested positive for ADA but had not received TCZ and were considered false positives. In parts 1 and 2 combined, among 199 patients who received ≥1 dose of TCZ, 193 (97%) were evaluable (Table); TCZ-induced ADA developed in 13 of these patients (6.7%) postbaseline (4 during part 1, 9 during part 2). Of these 13 patients, 8 (4.1%) had ADA with neutralizing potential and 1 (0.5%) had IgE ADA. Most TCZ-induced ADA were transient. There was no clear impact of TCZ-induced ADA on TCZ PK (Figure). No patients with TCZ-induced ADA experienced anaphylaxis, hypersensitivity reactions, or injection site reactions, and none withdrew because of lack of efficacyConclusion:In patients with GCA, treatment-induced ADA developed in a minority of patients and had no impact on TCZ PK, efficacy, or safety. The immunogenicity of subcutaneous TCZ treatment was low, consistent with that observed in patients with RA.References:[1]Burmester GR et al.Ann Rheum Dis2017;76:1078-85.[2]Stone JH et al.N Engl J Med2017;377:317-28.Table.Immunogenicity in Patients Who Received TCZ (part 1 + part 2)Patients Who Received TCZN = 199BaselineEvaluable patients194 (97.5)Positive screening assay12 (6.0)Positive confirmation assay6 (3.0)PostbaselineEvaluable patients193 (97.0)Treatment-induced ADA13 (6.7)Characterizaton of ADANeutralizing potential8 (4.1)IgE1 (0.5)Data are number (%) of patients based on N at baseline and on number of evaluable patients postbaseline.Disclosure of Interests:Min Bao Shareholder of: Roche, Employee of: Genentech, Navita L. Mallalieu Shareholder of: Roche, Employee of: Roche, John H. Stone Grant/research support from: Roche, Consultant of: Roche

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