Tocilizumab: A Novel Therapy for Large-vessel Vasculitis
Tocilizumab: A Novel Therapy for Large-vessel Vasculitis
Objective. Treatment of large-vessel vasculitis (LVV) remains challenging. Patients usually respond to glucocorticoid (GC) therapy, but often relapse on tapering of the GC dose or after GC withdrawal. In addition, GCs are fraught with numerous adverse events. The aim of this study was to assess the efficacy and safety of the anti-IL-6 receptor (IL-6R) antibody tocilizumab (TCZ) in patients with LVV.
Methods. Four patients with active LVV (two with GCA and two with Takayasu arteritis) received monthly TCZ infusions (8 mg/kg bodyweight) for 6 consecutive months. Two patients were treatment naïve, while two had relapsing disease. Disease activity and drug tolerability were assessed clinically and by laboratory tests at study entry and subsequently every month for 6 months of TCZ treatment, while an [F]fluorodeoxyglucose PET (PET/CT) scan was performed before and after treatment. In addition, a semi-quantitative clinical evaluation was performed at baseline and at 3 and 6 months using the Indian Takayasu activity score and the Kerr indices. After TCZ, MTX was used as maintenance therapy.
Results. All patients treated with TCZ therapy had a satisfactory clinical and laboratory response, while PET/CT findings significantly improved in all cases. No serious adverse events were noted. Only one patient had a transient increase in liver enzymes.
Conclusions. In this small group of patients with LVV, treatment with TCZ was effective and well tolerated. Further, larger studies are required to confirm our findings.
GCA and Takayasu arteritis (TA) are primary systemic vasculitides involving the aorta and its major branches. Glucocorticoids (GCs) are the mainstay of treatment of GCA and TA, but a sizeable number of patients relapse upon tapering of the GC dose or discontinuation of GC therapy. MTX has shown some efficacy as steroid-sparing agent in relapsing patients in both conditions, but the entity of the benefit was rather modest, at least in GCA. There is some evidence that biologic agents, especially TNF-α inhibitors, might be efficacious in patients with GCA and TA who are relapsing. However, in a randomized controlled trial, the anti-TNF-α mAb infliximab did not appear to confer a significant benefit in patients with newly diagnosed GCA over and above that provided by GC alone. Therefore, there is a need to develop novel, effective therapeutic strategies.
IL-6 is a key player in the pathogenesis of numerous inflammatory disorders, including GCA and TA. Emerging data suggest that blockade of the soluble IL-6 receptor (s-IL-6R) with the mAb tocilizumab (TCZ) might be beneficial for patients with refractory TA and GCA. The aim of this pilot study was to determine the efficacy and safety of TCZ in a small population of patients with large-vessel vasculitis (LVV).
Abstract and Introduction
Abstract
Objective. Treatment of large-vessel vasculitis (LVV) remains challenging. Patients usually respond to glucocorticoid (GC) therapy, but often relapse on tapering of the GC dose or after GC withdrawal. In addition, GCs are fraught with numerous adverse events. The aim of this study was to assess the efficacy and safety of the anti-IL-6 receptor (IL-6R) antibody tocilizumab (TCZ) in patients with LVV.
Methods. Four patients with active LVV (two with GCA and two with Takayasu arteritis) received monthly TCZ infusions (8 mg/kg bodyweight) for 6 consecutive months. Two patients were treatment naïve, while two had relapsing disease. Disease activity and drug tolerability were assessed clinically and by laboratory tests at study entry and subsequently every month for 6 months of TCZ treatment, while an [F]fluorodeoxyglucose PET (PET/CT) scan was performed before and after treatment. In addition, a semi-quantitative clinical evaluation was performed at baseline and at 3 and 6 months using the Indian Takayasu activity score and the Kerr indices. After TCZ, MTX was used as maintenance therapy.
Results. All patients treated with TCZ therapy had a satisfactory clinical and laboratory response, while PET/CT findings significantly improved in all cases. No serious adverse events were noted. Only one patient had a transient increase in liver enzymes.
Conclusions. In this small group of patients with LVV, treatment with TCZ was effective and well tolerated. Further, larger studies are required to confirm our findings.
Introduction
GCA and Takayasu arteritis (TA) are primary systemic vasculitides involving the aorta and its major branches. Glucocorticoids (GCs) are the mainstay of treatment of GCA and TA, but a sizeable number of patients relapse upon tapering of the GC dose or discontinuation of GC therapy. MTX has shown some efficacy as steroid-sparing agent in relapsing patients in both conditions, but the entity of the benefit was rather modest, at least in GCA. There is some evidence that biologic agents, especially TNF-α inhibitors, might be efficacious in patients with GCA and TA who are relapsing. However, in a randomized controlled trial, the anti-TNF-α mAb infliximab did not appear to confer a significant benefit in patients with newly diagnosed GCA over and above that provided by GC alone. Therefore, there is a need to develop novel, effective therapeutic strategies.
IL-6 is a key player in the pathogenesis of numerous inflammatory disorders, including GCA and TA. Emerging data suggest that blockade of the soluble IL-6 receptor (s-IL-6R) with the mAb tocilizumab (TCZ) might be beneficial for patients with refractory TA and GCA. The aim of this pilot study was to determine the efficacy and safety of TCZ in a small population of patients with large-vessel vasculitis (LVV).
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