Autor(en)
Iyza F Baig; Alexis Pascoe; Andrew G Lee
Titel
Exploring tocilizumab for giant cell arteritis cases
Teil von
  • Ophthalmology Times, 2018-08-01, Vol.43 (13), p.19-20
Ort / Verlag
Monmouth Junction: MultiMedia Healthcare Inc
Links zum Volltext
Quelle
Alma/SFX Local Collection
Beschreibungen
Drug shows promise; further studies may be needed for long-term safety profile, efficacy Giant cell arteritis (GCA) is a systemic vasculitis that produces a granulomatous inflammation of large- and medium-sized-arteries, most commonly involving the aorta and extracranial branches of the carotid arteries.1,2,3,4 Classically affecting patients over the age of 50 years, GCA is known to be the most common primary vasculitis affecting Western countries.2,3,4 While headaches, myocardial infarction, stroke, and claudication of the jaw are important clinical manifestations of GCA5, those relevant to an ophthalmological perspective include transient ischemic visual symptoms and permanent blindness (e.g., ischemic optic neuropathy or central retinal artery occlusion).1,3 Complications of the vasculitis can result from ischemia secondary to arterial occlusion, systemic inflammation, and aneurysm formation and rupture due to persistent arterial wall injury1; therefore, prompt and effective control of inflammation is essential. Earlier treatment may lead to more rapid symptomatic relief of headache, normalization of inflammatory markers, and reduction or prevention of vision loss after initiation.1,5,6 While corticosteroids have significantly decreased the incidence of blindness in patients with GCA, studies have shown that vascular inflammation persists even after corticosteroid therapy, al lowing for progressive occlusion of the affected vessels.1 In addition, since the majority of patients tend to flare as corticosteroid dosage is reduced, long-term treatment with a slow reduction of steroids is thereby necessary.3Unfortunately, long-term corticosteroid use can lead to significant comorbidities such as infection, fractures, cataracts, diabetes, and even psychosis.3 Consultation with the primary-care provider and/or rheumatologist may be necessary to help with treatment and management of side effects. Prior randomized controlled trials evaluating corticosteroid-sparing agents such as methotrexate and tumor necrosis factor inhibitors have failed or shown inconclusive or conflicting results.3,6 However, a randomized controlled trial has finally demonstrated a viable contender for maintaining corticosteroid remission in patients with GCA: the interleukin-б (IL- 6) receptor inhibitor, tocilizumab (TCZ).5 The rationale for blocking the receptor for IL-6 is based on the cytokine's central role in regulating both innate and acquired immunities .3 Produced by T-cells, B-cells, endothelial cells, fibroblasts, and macrophages, IL-6 has been shown to be increased in inflamed arteries, potentiating the inflammatory responses of GCA.3 A study by Weyand et al (2000) suggested that disease activity in GCA correlates with serum levels of IL-6, and that compared to erythrocyte sedimentation rate (ESR), IL-6 may be a more sensitive biological marker for disease activity in GCA patients who were untreated and treated with corticosteroids.1 Consequently, numerous studies (including a phase II trial) examining TCZ were performed, and results suggested the high efficacy of the IL-6 receptor inhibitor in inducing and maintaining remission in GCA.2'4 More recently, the results of the much awaited GiACTA trial, a 1-year, multicenter, randomized, controlled, double blind trial, show significant promise in the use of TCS for inducing and maintaining remission in GCAA5In the GiACTA trial, 251 patients were randomly assigned to one of four treatment groups:3 * 162 mg of subcutaneous TCZ weekly + 26week prednisone taper (cumulative prednisone dose = 1,862 mg) * 162 mg of subcutaneous TCZ every two weeks + 26-week prednisone taper (cumulative prednisone dose = 1,862 mg) * Placebo + 26-week prednisone taper (cumulative prednisone dose = 3,296 mg) * Placebo + 52-week prednisone taper (cumulative prednisone dose = 3818 mg) Sustained remission was defined as normalization of C-reactive protein (<1 mg/ dL) and absence of flare (signs and symptoms of GCA, ESR >30 mm/hour) from week 12 to week 52 while adhering to prednisone taper.5 Outcomes were measured at 52 weeks and included rates of corticosteroid-free remission maintained by each TCZ group compared with those of the placebo group treated with a 26-week prednisone taper and a 52-week taper prednisone taper.5 Results of the GiACTA trial showed that by 52 weeks, 56% of patients receiving TCZ weekly and 53% of those receiving it biweekly had achieved and sustained remission, compared to 14% of the placebo group on the 26-week prednisone taper, and 18% of those on the 52-week prednisone taper.5 Furthermore, 23% and 26% of those on TCZ weekly and biweekly had a flare, respectively, compared to 68% of those on the 26-week prednisone taper, and 49% of those on the 52-week taper.5 Safety of TCZ was also evaluated: 15% and 14% of the weekly and biweekly TCZ groups respectively reported serious adverse events, while those in the placebo 26-week taper and 52-week taper reported 22% and 25% adverse events respectively.5.
Format
Sprache(n)
Englisch
Identifikator(en)
ISSN: 0193-032X
ISSN: 2150-7333
Links zum Inhalt
Schlagwörter
Arthritis, Clinical trials, Cytokines, Drug dosages, Inflammation, Medical personnel, Ophthalmology, Rheumatism, Veins & arteries
Systemstelle
Signatur

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