Corticosteroid-free treatment of tocilizumab monotherapy for microscopic polyangiitis: a single-arm, single-center, clinical trial

Sakai, Ryota; Kondo, Tsuneo; Kikuchi, Jun; Shibata, Akiko; Chino, Kentaro; Okuyama, Atsushi; Takei, Hiroyuki; Amano, Koichi

doi:10.3109/14397595.2016.1160968

Cited by 18 publications

(12 citation statements)

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“…TCZ (8 mg/kg) was administered at fortnightly intervals for the first 8 weeks (5 infusions) and then every 4 weeks for the next 40 weeks (10 infusions). Fortnightly infusions of TCZ were used to suppress the high disease activity of PMR as soon as possible, according to the dosage and administration for systemic juvenile idiopathic arthritis (JIA) or Castleman's disease, as previously described . An intense regimen of fortnightly infusions in the early phase of PMR is reasonable because the quality of life of most patients with PMR is substantially affected by the disease, although serum CRP levels are not as high as the levels observed in patients with JIA.…”

Section: Methodsmentioning

confidence: 99%

Tocilizumab monotherapy for polymyalgia rheumatica: A prospective, single‐center, open‐label study

et al. 2019

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| INTRODUC TI ONPolymyalgia rheumatica (PMR) is a systemic inflammatory disease of unknown etiology. It mainly affects elderly people and rarely arises in people younger than 50 years old. Typical clinical features of PMR include proximal myalgia (particularly in the shoulder girdles), morning stiffness of the trunk, and elevated erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP) levels. 1,2 Glucocorticoids (GC) remain the mainstay therapy for PMR 2,3 because they produce dramatic responses in most patients. However, approximately half of patients with PMR experience relapse after tapering of the GC dose. 2,4 Moreover, long-term GC therapy can produce substantial adverse events, such as osteoporotic compression fractures of the spine, diabetes, infections and cardio-cerebral vascular events. 2,5,6 Abstract Objectives: Polymyalgia rheumatica (PMR) is a systemic inflammatory disease in the elderly of unknown etiology. While glucocorticoids are the mainstay of treatment for PMR, various glucocorticoid-related adverse events are common. Recently, several studies have reported the efficacy of tocilizumab (TCZ), an anti-interleukin-6 receptor antibody, for PMR treatment in addition to an accompanying reduction, or even tapering-off, of glucocorticoids in some cases. The objective of this study was to elucidate the efficacy of TCZ monotherapy in the absence of glucocorticoids for PMR. Method:We conducted a 2-year, prospective, single-center, open-label pilot study of TCZ monotherapy in patients with PMR. TCZ (8 mg/kg) was administered at fortnightly intervals for the first 2 months and monthly over the next 10 months.Subsequently, patients were observed for another year without any treatment. The primary endpoints were the remission rates at weeks 12 and 52, and the secondary endpoints were the relapse rate and safety over the total 104 weeks.Results: Thirteen patients were included in this study. Four of these patients achieved remission at week 12 (remission rate 31%). Four patients withdrew from the study due to adverse events (n = 2) and inefficacy (n = 2). At week 52, all 9 patients who had completed the first year achieved remission. Eight patients completed the drug-free second year, with 7 maintaining remission.Conclusions: TCZ monotherapy is well tolerated and can lead to remission in most patients with PMR in the absence of glucocorticoids. K E Y W O R D Sglucocorticoid, interleukin-6, monotherapy, polymyalgia rheumatica, tocilizumab agents. We used 15 infusions of TCZ. However, if fewer TCZ infusions are sufficient to control PMR and TCZ treatment could be ceased, then these cost problems would be negated. Therefore, the optimal number of infusions of TCZ required to control PMR activity must be determined in the future. In addition, as TCZ monotherapy is expected to reduce adverse events related to GCs, such as osteoporosis, diabetes, dyslipidemia, and so on, the additional costs associated with the treatment of these adverse events will be reduced.Several limitations of our study warran...

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Section: Methodsmentioning

confidence: 99%

Tocilizumab monotherapy for polymyalgia rheumatica: A prospective, single‐center, open‐label study

et al. 2019

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“…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 ].…”

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

163

129

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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.

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“…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]. All patients received 8 mg/kg of intravenous TCZ biweekly for the first 2 months (5 courses), and monthly for the next 10 months (10 courses).…”

Section: Anca-associated Vasculitismentioning

confidence: 99%

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

Kondo

Amano

2018

Immunological Medicine

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Glucocorticoids (GCs) have played a pivotal role in the treatment of immune-mediated inflammatory diseases (IMIDs) for a long time. However, GCs also incur a significant risk of undesirable adverse events such as Cushingoid changes, osteoporosis, glaucoma and metabolic abnormalities such as diabetes and hypercholesterolemia, which may lead to lifethreatening cerebrovascular and cardiovascular events. High-dose GCs may also cause mental disorders and osteonecrosis. Recently, new therapeutic strategies have been developed to reduce the dose or even eliminate the need for GCs; multi-target drug therapies for systemic lupus erythematosus (SLE), biological agents such as tocilizumab and rituximab for systemic vasculitis, and anakinra and tocilizumab for adult-onset still's disease. Therefore, the era of GC-sparing or GC-free treatment for IMIDs is on the horizon.

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Corticosteroid-free treatment of tocilizumab monotherapy for microscopic polyangiitis: a single-arm, single-center, clinical trial

Abstract: TCZ monotherapy may be an alternative treatment strategy in some patients with MPA.

Cited by 18 publications

References 43 publications

Tocilizumab monotherapy for polymyalgia rheumatica: A prospective, single‐center, open‐label study

Tocilizumab monotherapy for polymyalgia rheumatica: A prospective, single‐center, open‐label study

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

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

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