A case of polyangiitis overlap syndrome of giant cell arteritis and granulomatosis with polyangiitis successfully treated with rituximab.

We report a case of polyangiitis overlap syndrome of giant cell arteritis (GCA) and granulomatosis with polyangiitis (GPA) and conduct a literature review of polyangiitis overlap syndrome. The patient was 73-year-old male who developed cranial-type GCA and GPA simultaneously and was successfully treated with rituximab. Rituximab might be effective for not only GPA but also GCA.

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

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.

Efficacy and tolerability of six-week extended dosing interval with tocilizumab therapy in a prospective cohort as remission maintenance in patients with rheumatoid arthritis.

OBJECTIVES: To prospectively evaluate the efficacy and tolerability of a six-week extended dosing interval with tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) in sustained remission. METHODS: Patients who received over six doses of intravenous TCZ in clinical remission (disease activity score [DAS] 28 - erythrocyte sedimentation rate [ESR] ≤ 2.6) maintained over 3 months between December 2013 and December 2015 were included. Flare was defined as DAS28-ESR >3.2 at two consecutive visits. RESULTS: Twenty-five patients were enrolled; 87.5% achieved clinical remission at week 54 after six-week extension and 95.5% achieved a van der Heijde modified total Sharp score (ΔmTSS) ≤0.5. The Health Assessment Questionnaire Disability Index (HAQ-DI) did not increase during 54 weeks. HAQ-DI at baseline and ΔDAS28-ESR at week six positively correlated with increase in DAS28-ESR at week 54. ΔSwollen joint count at week six positively correlated with ΔmTSS at week 54. A total of 12 adverse events occurring in 10 patients did not lead to cessation of TCZ except for one case of recurrent lymphoproliferative disorder at week five. CONCLUSION: 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.

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.

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.

A case of multiple giant coronary aneurysms and abdominal aortic aneurysm coexisting with IgG4-related disease.

IgG4-related disease (IgG4RD) is a unique systemic lymphoproliferative disorder characterized by elevated serum IgG4 levels and IgG4-producing plasma cell expansion in the affected tissues, which are accompanied by fibrotic or sclerotic changes. Vascular lesions may also be a part of IgG4RD as a number of case reports have discussed inflammatory abdominal aortic aneurysms associated with IgG4RD, but coronary artery lesions seem to be rare complications of IgG4RD. A 71-year-old man suffered from multiple giant coronary aneurysms and an abdominal aortic aneurysm with concurrent pancreatic, gall bladder, bile duct, and salivary gland lesions resulting from IgG4RD. The present observations suggest that coronary aneurysms may also develop as a consequence of this disease.

CD3 ζ defects in systemic lupus erythematosus.

The prototype autoimmune disease, systemic lupus erythematosus (SLE), has been known to be associated with deficiency of ζ chain, a component of the T-cell receptor-CD3 complex. Comprehensive analysis has shown that expression of the CD3 ζ chain is attenuated or absent in over half of SLE patients. Furthermore, aberrant transcripts of the CD3 ζ chain, including spliced variants lacking exon 7 or having a short 3'-untranslated region, have been detected in SLE T cells. Although attenuated expression of the CD3 ζ chain is also observed in cancer patients, infections and other autoimmune diseases, sustained attenuation of the CD3 ζ expression accompanied with aberrant transcripts are only observed in SLE. In this study, the authors review the unique features of CD3 ζ defects observed in SLE and discuss the molecular basis of the defects by recent findings in animal models, single-nucleotide polymorphisms and genome-wide association studies.

Successful treatment of adult-onset Still's disease with tocilizumab monotherapy: two case reports and literature review.

Adult-onset Still's disease (AOSD) is a systemic inflammatory disease of unknown etiology. Recently, it has been reported that quite a few cases of refractory AOSD were successfully treated with tocilizumab (TCZ) and corticosteroids were withdrawn in some of these patients. We report two AOSD patients who were treated successfully with TCZ monotherapy; thus, avoiding corticosteroid treatment. Because both of the patients refused to take corticosteroids, we planned to treat them with 8 mg/kg of TCZ monotherapy at weeks 0, 2, 6 and subsequently every 4 weeks. The efficacy of TCZ was assessed by patients' clinical symptoms such as fever, arthralgia, skin eruptions, and laboratory markers such as serum levels of CRP, ferritin, and IL-6. We also reviewed 14 previous case reports including 30 cases who had been treated with TCZ for AOSD. Our patients responded rapidly and have been maintained in clinical remission without corticosteroid treatment. In the literature review, concomitant corticosteroid treatment described in 13 cases was successfully tapered in 7 and discontinued in 6 cases. TCZ monotherapy can be a candidate for the first-line therapy for some AOSD patients.