Treatment of polyarteritis nodosa with tocilizumab: a new therapeutic approach?

Interleukein-6 (IL-6), is produced locally from infectious or injured lesions and is delivered to the whole body via the blood stream, promptly activating the host defense system to perform diverse functions. However, excessive or sustained production of IL-6 is involved in various diseases. In diseases, the IL-6 inhibitory strategy begins with the development of the anti-IL-6 receptor antibody, tocilizumab (TCZ). This antibody has shown remarkable effects on Castleman disease, rheumatoid arthritis and juvenile idiopathic arthritis. In 2017, TCZ was proven to work effectively against giant cell arteritis, Takayasu arteritis and cytokine releasing syndrome, initiating a new era for the treatment of these diseases. In this study, the defensive functions of IL-6 and various pathological conditions are compared. Further, the diseases of which TCZ has been approved for treatment are summarized, the updated results of increasing off-label use of TCZ for various diseases are reviewed and the conditions for which IL-6 inhibition might have a beneficial role are discussed. Given the involvement of IL-6 in many pathologies, the diseases that can be improved by IL-6 inhibition will expand. However, the important role of IL-6 in host defense should always be kept in mind in clinical practice.

Section: Therapeutic Targeting Of Il-6 In Diseasesmentioning

confidence: 99%

The Two-Faced Cytokine IL-6 in Host Defense and Diseases

Narazaki

Kishimoto

2018

IJMS

169

129

“…Indeed, treatment of skin necrosis with in iximab appeared effective in our study. Although not used in the current study, the interleukin-6 blocker tocilizumab has also shown promise for the treatment of vasculitis [31,32]. Strategies that aim to reduce the treatment burden as much as possible should be a major goal for physicians when attempting to achieve remission.…”

Section: Discussionmentioning

confidence: 97%

Clinical presentations and long-term prognosis of childhood-onset polyarteritis nodosa in a single centre: a retrospective study

Kim

2020

Preprint

Background: Polyarteritis nodosa (PAN) is a systematic necrotizing vasculitis involving medium-sized arteries. Childhood-onset PAN ranges from mild to severe systematic disease causing damage and early mortality. As it is a rare disease in children, there is less study on clinical features, diagnosis and treatment than adults. And diagnosis occurs relatively late in most paediatric patients with polyarteritis nodosa. Therefore, this study aimed to investigate clinical manifestations, laboratory findings, treatment strategies, and long-term outcomes among patients with childhood-onset polyarteritis nodosa treated at a single-centre in Korea. We further aimed to evaluate the usefulness of the Birmingham Vasculitis Activity Score (BVAS) and Five-Factor Score (FFS) in paediatric patients.Methods: We retrospectively analysed data collected from patients with childhood-onset PAN treated at our institution from March 2003 to February 2020. Results: Nine patients (6 male and 3 female) were included in the study. The median ages at symptom onset and diagnosis were 7.6 (3–17.5) and 7.7 (3.5–17.6) years, respectively. The median follow-up duration was 7.0 (1.6–16.3) years. Eight patients were diagnosed with systemic PAN, while one was diagnosed with cutaneous PAN. All patients exhibited skin manifestations, while five exhibited Raynaud’s phenomenon. Organ involvement was observed in one patient. Constitutional symptoms such as fever, arthralgia, myalgia, and weight loss were also observed. Antineutrophil cytoplasmic antibodies were absent in all patients. The median BVAS at diagnosis was 8 (range: 2–29), and one patient had an FFS of 1. Prednisolone was initially used for induction in all patients, and other drugs were added in cases refractory to prednisolone. All patients survived despite some complications such as intracranial haemorrhage or digital necrosis requiring amputation.Conclusions: Early diagnosis and treatment may minimise sequelae in patients with childhood-onset PAN. Further multicentre studies are required to clarify the unique characteristics of childhood-onset PAN and establish treatment guidelines, early detection strategies, and biomarkers. Trial registration: Retrospectively registered.

“…Infliximab appeared to be effective in treating skin necrosis in our study. Although not used in the current study, the interleukin-6 blocker tocilizumab has also shown promise for the treatment of vasculitis 29 , 30 . Strategies that aim to reduce the treatment burden as much as possible should be a major goal for physicians when attempting to achieve remission.…”

Section: Discussionmentioning

confidence: 99%

Clinical presentations and long term prognosis of childhood onset polyarteritis nodosa in single centre of Korea

Kim

2021

Sci Rep

Childhood-onset polyarteritis nodosa (PAN) is a rare and systemic necrotising vasculitis in children affecting small- to medium-sized arteries. To date, there have been only a few reports because of its rarity. Thus, we aimed to investigate the clinical manifestations, laboratory findings, treatment, and long-term outcomes in patients with childhood-onset PAN and to evaluate the usefulness of the paediatric vasculitis activity score (PVAS). We retrospectively analysed the data of nine patients with childhood-onset PAN from March 2003 to February 2020. The median ages at symptom onset, diagnosis, and follow-up duration were 7.6 (3–17.5), 7.7 (3.5–17.6), and 7.0 (1.6–16.3) years, respectively. All patients had constitutional symptoms and skin manifestations, while five exhibited Raynaud’s phenomenon. Organ involvement was observed in one patient. The median PVAS at diagnosis was 7 (range: 2–32). Prednisolone was initially used for induction in all patients, and other drugs were added in cases refractory to prednisolone. All patients survived, but three patients with high PVAS at diagnosis experienced irreversible sequelae, including intracranial haemorrhage and digital amputation. In conclusion, early diagnosis and treatment may minimise sequelae in patients with childhood-onset PAN. This study suggests that high PVAS score at diagnosis may be associated with poor prognosis.