| 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...

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.

Background Pulsed cyclophosphamide or mycophenolate mofetil for lupus nephritis has limited efficacy. We previously reported a case of mixed-class IV + V lupus nephritis successfully treated with cyclophosphamide and tacrolimus. This study assessed the efficacy and safety of multitarget therapy with cyclophosphamide and tacrolimus for the treatment of lupus nephritis. Methods In a prospective, single-arm, open label pilot study, we recruited 15 patients aged 18-64 years with active lupus nephritis who met the American College of Rheumatology criteria for a diagnosis of systemic lupus erythematosus (1997). The treatment protocol was a starting dose of prednisolone of 0.6-1.0 mg/kg/day for 2 weeks and then tapered to a maintenance dose, intravenous cyclophosphamide (500 mg biweekly for 3 months) and tacrolimus (3.0 mg/day). Tacrolimus was continued as maintenance therapy. Complete remission was defined as a spot urine protein/creatinine ratio of < 0.5 g/gCr with no active urine casts and a serum creatinine level that was either normal or within 30% of a previously abnormal baseline level. We retrospectively compared results for the study patients with those of 18 historical controls conventionally treated with cyclophosphamide and prednisolone. Results At baseline, the mean patient age was 41.5 ± 14.6 years (male:female ratio 2:13), urine protein/creatinine ratio 3.9 ± 2.3 g/gCr and serum creatinine 84.6 ± 34.6 µmol/L. Lupus nephritis classifications included classes IV ( n = 8), III + V ( n = 1), IV + V ( n = 5) and unclassified ( n = 1). Eleven patients completed the treatment protocol and four withdrew. At 6 months, 12 of 15 (80.0%) had achieved complete remission using intention-to-treat analysis, significantly more than historical controls (seven of 18 patients, 38.9%). A transient increase in serum creatinine and gastric symptoms occurred in three cases. One patient withdrew due to cytomegalovirus antigenemia and severe diabetes, and one patient died of thrombotic microangiopathy. Conclusions Multitarget therapy with cyclophosphamide and tacrolimus can be a therapeutic option for lupus nephritis. Clinical trials registration Combination therapy of tacrolimus and intravenous cyclophosphamide for remission induction of lupus nephritis, UMIN: 000004893, URL: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000005830&language=E . Date of registration: 18 January 2011.

A six-week extended dosing interval of TCZ for patients with RA in sustained remission is proposed as an acceptable treatment option for maintaining efficacy and tolerability.

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

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A substantial number of patients with lupus nephritis (LN) are refractory to conventional glucocorticoid (GC) treatment. Although many of these patients respond to immunosuppressive drugs such as intravenous cyclophosphamide (IVCY), azathioprine (AZA), mizoribine, tacrolimus, cyclosporine A (CSA) and mycofenolate mofetil (MMF), some remain refractory to such therapies. Recent studies of multi-target therapies have reported effective outcomes for immunosuppression following renal transplantation and refractory LN when therapy consists of two or more immunosuppressive drugs with different mechanisms of action. We herein report a case of LN unresponsive to IVCY that was successfully treated with the addition of tacrolimus and discuss the usefulness of multi-target therapy for LN.

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