Current clinical evidence of tocilizumab for the treatment of ANCA-associated vasculitis: a prospective case series for microscopic polyangiitis in a combination with corticosteroids and literature review

Abstract

The purpose of this study is to report the efficacy and safety of a combination of tocilizumab (TCZ) and high-dose corticosteroid (CS) in two patients with microscopic polyangiitis (MPA) and review the published current clinical evidence on TCZ in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), except for large vessel vasculitis (LVV) and polymyalgia rheumatica (PMR). Two MPA patients were treated with TCZ at 8 mg/kg every month for 1 year and CS (prednisolone 1 mg/kg/day for 2 weeks, followed by tapering) in a prospective single-arm, single-center, cohort, open-label pilot study (UMIN clinical trials: 000012072). We performed a systematic literature search (PubMed and ICHUSHI [Japan Medical Abstracts Society] until June 30, 2017) to identify published reports on patients with all vasculitis other than LVV/PMR, who were treated with TCZ. We successfully treated the first patient. However, the other patient had serious infection probably associated with the combination of TCZ and high-dose CS. The literature review identified 22 reports with a total of 34 patients who received TCZ for AAV, rheumatoid vasculitis, and other types of vasculitis, in addition to our patients. In 15 of 17 patients (88.2%) with primary and secondary AAV, especially MPA, TCZ induced clinical remission, although TCZ use for rheumatoid vasculitis and vasculitis with mucocutaneous lesions is controversial. This study suggested that TCZ therapy is a potential treatment strategy for patients with AAV. However, TCZ combined with high-dose of CS might not be an appropriate treatment. Future studies are needed to confirm our findings.

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

“…Case reports have shown TCZ to be effective for a variety of other diseases, including autoimmune hemolytic anemia [ 171 , 172 ], reactive arthritis [ 173 ], autoimmune encephalitis [ 174 , 175 ], myasthenia gravis [ 176 ], Blau syndrome [ 177 ], anti-Caspre2 syndrome [ 178 ], refractory organizing pneumonia associated with Sjögren’s syndrome [ 179 ], cancer-related cachexia [ 180 ] and steroid refractory immune-mediated adverse events secondary to immune check point inhibitors [ 181 ]. Besides large vessel vasculitis, several case reports have indicated that TCZ has effects on rheumatoid vasculitis [ 182 ], polyarteritis nodosa [ 183 , 184 ], microscopic polyangiitis [ 185 , 186 ] and cryoglobulinemia vasculitis [ 187 ]. A report showed that epidural administration of TCZ reduced pain due to sciatica with lumbar spinal stenosis [ 188 ].…”

Era of steroid sparing in the management of immune-mediated inflammatory diseases

“…Several reports have suggested TCZ as a potential treatment for AAV as well as LVV [38]. The use of concomitant GC is a significant risk factor for developing serious infections during TCZ treatment [39]. Therefore, based on our experience that TCZ monotherapy without GC and CYC led to the successfully remission of a patient with AAV complicated with RA, we conducted a prospective single-arm, singlecenter, cohort, pilot study on the efficacy of TCZ monotherapy for 7 MPA patients [40].…”

Immunopathogenesis of ANCA-Associated Vasculitis

“…A recent review of the literature identified 17 cases who received tocilizumab in the management of ANCA-associated vasculitis. A majority (88.2%) achieved remission following IL-6R blockade with tocilizumab [ 160 ]. It is likely that more evidence will derive from the current Coronavirus Disease 2019 (COVID-19) pandemic, as tocilizumab is considered as a rather safe alternative to other immunosuppressive measures [ 161 ].…”