**3.6 Tocilizumab**

Tocilizumab is a humanized monoclonal antibody that binds to membranebound and soluble Interleukin 6 receptors and inhibits Interleukin 6 signaling pathways [28].

A study assessed eight patients who had refractory Takayasu arteritis. Two cases were refractory to Infliximab and three did not reach remission on steroids and methotrexate. Altogether eight patients received Tocilizumab and were followed for 18 months. Of these eight patients, seven achieved remission. This shows that Tocilizumab can be a potential therapy for patients with Takayasu arteritis refractory to anti-TNF alpha therapy [29].

A retrospective study assessed the effectiveness of Tocilizumab in complicated large vessel vasculitis. Patients were treated with Tocilizumab out of which eight had giant cell arteritis, two had large vessel vasculitis associated with rheumatoid arthritis and one had Takayasu arteritis. These patients were followed for 23 months. At the end of duration, seven patients were in remission, one patient relapsed after discontinuing the drug, and one patient suffered from serious infective complication. Two patients died, although cause of death was not attributable to the use of Tocilizumab. Three relapses occurred but remission was regained by switching the usual subcutaneous administration of Tocilizumab to intravenous [30].

Glucocorticoids are the conventional treatment for giant cell arteritis but adverse effects are common, so are the relapses, soon after tapering the steroids. Although the exact cause of death is not known, cytokines such as tumor necrosis factor alpha and Interleukin 6 have been implicated. A retrospective study included 134 patients from 40 different centers who were diagnosed with giant cell arteritis either by temporal artery biopsy or imaging techniques. All these patients had received high dose of steroids in past and majority of patients had been given biologic immunosuppressives such as Abatacept, Infliximab or Rituximab. Tocilizumab was given either intravenously (8 mg/kg 4 weeks apart) or subcutaneously (162 mg/week). At the end of 1 month the ESR and CRP had fallen and percentage of patients with anemia had decreased. Those who were followed for 2 years, amongst them 39 were seen


#### **Table 6.**

*Tocilizumab trials [29–31].*


#### **Table 7.**

*Commonly used biological agents in the treatment of systemic vasculitis.*

in remission with acute phase reactants within normal limits and minimum steroid dose (0–5 mg/day). However, after an average follow up of 12 months, 32 patients reported an adverse infection because of which 17 patients had to discontinue the therapy [31].

Tocilizumab works against the pro-inflammatory cytokine Interleukin 6 and has proven its efficacy in Takayasu arteritis that has failed to respond to Infliximab. Giant cell arteritis, non responsive to various other biological agents, has reacted remarkably to Tocilizumab by achieving disease remission in most of the cases. Despite all its applauding outcomes, life-threatening infection remains a serious complication.

**Table 6** shows outcomes of studies that have evaluated the effectiveness of Tocilizumab in different types of vasculitis.

**Table 7** summarizes the commonly used agents to treat systemic vasculitis, as discussed in this chapter, along with its mechanism of action and dosages.

#### **4. Conclusion**

In recent times use of high dose corticosteroids, cytotoxic and immunosuppressant drugs has improved the prognosis of systemic vasculitis dramatically. However, some patients still do not respond to conventional therapy or may not achieve remission. Few of them would relapse and a large number of patients develop illness secondary to the adverse effects caused by long term use of these drugs. The advent

**165**

**Author details**

Muhammad Ishaq Ghauri and Muhammad Shariq Mukarram\*

\*Address all correspondence to: shariq.msm@gmail.com

provided the original work is properly cited.

Department of Medicine, Jinnah Medical College Hospital, Karachi, Pakistan

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

*Treatment of Vasculitis: Beyond the Basics DOI: http://dx.doi.org/10.5772/intechopen.92729*

**5. Methods used for research of articles**

abstracts and by searching textbooks of Rheumatology.

market in near future [32].

of biological agents has not just let to a better understanding of pathophysiology of systemic vasculitis, but has also proved to be safe and efficacious. Among these agents, anti-TNF and anti-B cell therapy have been the first choice in many cases. Although clinical data are still insufficient, these agents seem to occupy most of the

We collected information by systematic review of the PubMed, scientific

### *Treatment of Vasculitis: Beyond the Basics DOI: http://dx.doi.org/10.5772/intechopen.92729*

*Vascular Biology - Selection of Mechanisms and Clinical Applications*

**Study Agent Disease Outcome**

Tocilizumab GCA, RA

**Agent Mechanism of action Dosage**

Belimumab Monoclonal antibody that inhibits B cell activating factor

Mepolizumab Monoclonal antibody directed against Interleukin 5

Tocilizumab Monoclonal antibody directed against Interleukin 6

*Commonly used biological agents in the treatment of systemic vasculitis.*

Rituximab Monoclonal antibody directed against CD20 500 mg intravenous Infliximab Anti-TNF alpha 5 mg/kg intravenous Etanercept Anti-TNF alpha 25 mg intravenous

Mejla et al. Tocilizumab TA Seven out of eight cases refractory to

vasculitis, TA

10 mg/kg intravenous

either Infliximab or methotrexate achieved

After follow up of 23 months, seven were in remission, one relapse after stopping the drug, three relapses but regained remission

out of them 39 were seen in remission. These patients had already taken biologics including Abatacept, Infliximab and Rituximab

remission

Tocilizumab GCA Patients who were on follow up till 2 years,

300 mg subcutaneous

subcutaneous

8 mg/kg intravenous 162 mg

in remission with acute phase reactants within normal limits and minimum steroid dose (0–5 mg/day). However, after an average follow up of 12 months, 32 patients reported an adverse infection because of which 17 patients had to discontinue the

Tocilizumab works against the pro-inflammatory cytokine Interleukin 6 and has proven its efficacy in Takayasu arteritis that has failed to respond to Infliximab. Giant cell arteritis, non responsive to various other biological agents, has reacted remarkably to Tocilizumab by achieving disease remission in most of the cases. Despite all its applauding outcomes, life-threatening infection remains a serious

**Table 6** shows outcomes of studies that have evaluated the effectiveness of

discussed in this chapter, along with its mechanism of action and dosages.

**Table 7** summarizes the commonly used agents to treat systemic vasculitis, as

In recent times use of high dose corticosteroids, cytotoxic and immunosuppressant drugs has improved the prognosis of systemic vasculitis dramatically. However, some patients still do not respond to conventional therapy or may not achieve remission. Few of them would relapse and a large number of patients develop illness secondary to the adverse effects caused by long term use of these drugs. The advent

**164**

therapy [31].

Toc in large vessel vasculitis (Marc Schmalzing)

IL-6 blocker exceeds (Nancy Walsh)

*Tocilizumab trials [29–31].*

**Table 7.**

**Table 6.**

complication.

**4. Conclusion**

Tocilizumab in different types of vasculitis.

of biological agents has not just let to a better understanding of pathophysiology of systemic vasculitis, but has also proved to be safe and efficacious. Among these agents, anti-TNF and anti-B cell therapy have been the first choice in many cases. Although clinical data are still insufficient, these agents seem to occupy most of the market in near future [32].
