Quantitative Analysis of Glassy State Relaxation and Ostwald Ripening during Annealing Using Freeze-Drying Microscopy.

Supercooling during the freezing of pharmaceutical solutions often leads to suboptimal freeze-drying results, such as long primary drying times or a collapse in the cake structure. Thermal treatment of the frozen solution, known as annealing, can improve those issues by influencing properties such as the pore size and collapse temperature of the lyophilisate. In this study we aimed to show that annealing causes a rearrangement of water molecules between ice crystals, as well as between the freeze-concentrated amorphous matrix and the crystalline ice phase in a frozen binary aqueous solution.

Selection of treatment regimens based on shared decision-making in patients with rheumatoid arthritis on remission in the FREE-J study.

Objective: To compare the outcome of various treatment de-escalation regimens in patients with RA who achieved sustained remission.

Methods: At period 1, 436 RA patients who were treated with MTX and bDMARDs and had maintained DAS28(ESR) at <2.6 were divided into five groups based on shared patient/physician decision-making; continuation, dose reduction and discontinuation of MTX or bDMARDs.

A nationwide questionnaire survey on the prevalence of ankylosing spondylitis and non-radiographic axial spondyloarthritis in Japan.

Objective: This nationwide study aimed to reveal the prevalence of ankylosing spondylitis (AS), non-radiographic axial spondyloarthritis (nr-ax SpA), and the positivity rate of human leukocyte antigen (HLA) among such patients in Japan.

Methods: The first survey was conducted in 2221 randomly selected facilities (26.3%) in September 2018, where the patients with AS/nr-ax SpA were taken care of from January to December 2017.

Long-term efficacy and safety of tocilizumab in refractory Takayasu arteritis: final results of the randomized controlled phase 3 TAKT study.

Objective: To investigate the long-term efficacy and safety of the IL-6 receptor antibody tocilizumab in patients with Takayasu arteritis (TAK).

Methods: Patients completing the randomized, double-blind, placebo-controlled period of the TAKT (Takayasu arteritis Treated with Tocilizumab) trial were followed up during open-label extended treatment with weekly s.c.

Clinicopathologic characteristics of 342 patients with multicentric Castleman disease in Japan.

To assess the clinicopathologic features of Multicentric Castleman disease (MCD) patients in Japan. We assessed baseline data for 342 Japanese MCD patients with a biopsy-proven diagnosis, enrolled in a prospective, observational study for tocilizumab treatment. Of 342 patients, 86.

Total Ankle Arthroplasty for Rheumatoid Arthritis in Japanese Patients: A Retrospective Study of Intermediate to Long-Term Follow-up.

Background: Outcomes after total ankle arthroplasty (TAA) combined with additive techniques (augmentation of bone strength, control of soft-tissue balance, adjustment of the loading axis) for the treatment of rheumatoid arthritis were evaluated after intermediate to long-term follow-up. The influences of biologic treatment on the outcomes after TAA were also evaluated.

Methods: We performed a retrospective observational study involving 50 ankles (44 patients) that underwent TAA for the treatment of rheumatoid arthritis.

Predictive factors for structural remission using abatacept: Results from the ABROAD study.

Objective: To investigate the effect of abatacept (ABA) on preventing joint destruction in biological disease-modifying anti-rheumatic drug (bDMARD)-naïve rheumatoid arthritis (RA) patients in real-world clinical practice.

Patients And Methods: RA patients were collected from the ABROAD (ABatacept Research Outcomes as a First-line Biological Agent in the Real WorlD) study cohort. They had moderate or high disease activity and were treated with ABA as a first-line bDMARD.

Evidence-based clinical practice guideline for adult Still's disease.

Objectives: Using an expert- and data-driven methodology, we have constructed the first clinical practice guidelines (CPGs) for adult Still's disease (ASD) after complete systematic review (SR) of the literature based upon the Medical Information Network Distribution Service (Minds) procedure.

Methods: The CPG committee for ASD organized by the Research Team for Autoimmune Diseases, the Research Program for Intractable Disease of the Japanese Ministry of Health, Labour, and Welfare has developed CPG for ASD 2017, according to the procedure proposed by Minds. The CPG development process includes (1) clarification of the purpose of CPG, (2) organization of the steering committee, (3) organization of the CPG committee and secretariat, (4) defining the scope (setting of clinical questions (CQs)), (5) SR, (6) development of recommendations, (7) drafting the CPG, (8) external evaluation and public comments, and (9) release.

Efficacy and safety of tocilizumab in patients with refractory Takayasu arteritis: results from a randomised, double-blind, placebo-controlled, phase 3 trial in Japan (the TAKT study).

Objective: To investigate the efficacy and safety of the interleukin-6 receptor antibody tocilizumab in patients with Takayasu arteritis (TAK).

Methods: Patients with TAK who had relapsed within the previous 12 weeks were induced into remission with oral glucocorticoid therapy. In this double-blind, placebo-controlled trial, patients were randomly assigned 1:1 to receive weekly tocilizumab 162 mg or placebo subcutaneously, and oral glucocorticoids were tapered 10 %/week from week 4 to a minimum of 0.

Tentative diagnostic criteria and disease severity classification for Castleman disease: A report of the research group on Castleman disease in Japan.

Objectives: To determine the tentative diagnostic criteria and disease severity classification for Castleman disease (CD) and describe the clinical and pathologic features among human herpesvirus 8 (HHV-8) negative idiopathic multicentric CD (iMCD) in the Japanese population.

Methods: We established the working groups for the research of CD in Japan and had meetings to discuss and define the tentative diagnostic criteria and disease severity classification for CD. We subsequently analyzed 142 patients classified into iMCD by using the nationwide Japanese patient registry.

Comparison of clinical and pathological features of lung lesions of systemic IgG4-related disease and idiopathic multicentric Castleman's disease.

Aims: The lung lesion [immunoglobulin (Ig)G4-L] of IgG4-related disease (IgG4-RD) is a condition that occurs together with IgG4-RD and often mimics the lung lesion [idiopathic multicentric Castleman's disease (iMCD-L)] of idiopathic multicentric Castleman's disease (iMCD). Because no clinical and pathological studies had previously compared features of these diseases, we undertook this comparison with clinical and histological data.

Methods And Results: Nine patients had IgG4-L (high levels of serum IgG4 and of IgG4 cells in lung specimens; typical extrapulmonary manifestations).

Differences in Predictive Factors for Sustained Clinical Remission with Abatacept Between Younger and Elderly Patients with Biologic-naive Rheumatoid Arthritis: Results from the ABROAD Study.

Objective: To differentiate predictive factors for sustained clinical remission between elderly and younger patients with rheumatoid arthritis (RA) receiving abatacept (ABA) as an initial biological disease-modifying antirheumatic drug.

Methods: The study involved 277 biologic-naive patients with RA with high or moderate disease activity, who were treated with intravenous ABA and evaluated for 48 weeks in 43 Japanese hospitals and rheumatology clinics (the ABatacept Research Outcomes as a First-line Biological Agent in the Real WorlD study: UMIN000004651). Predictive factors associated with sustained clinical remission defined by the 28-joint Disease Activity Score with C-reactive protein (DAS28-CRP) during the 24-48-week or 36-48-week periods were determined in elderly (≥ 65 yrs, n = 148) and younger patient groups (< 65 yrs, n = 129) using logistic regression analysis.

Effectiveness and safety of tocilizumab in achieving clinical and functional remission, and sustaining efficacy in biologics-naive patients with rheumatoid arthritis: The FIRST Bio study.

Objective: To evaluate effectiveness and safety of tocilizumab (TCZ) in biologic-naive Japanese patients with rheumatoid arthritis (RA) in real-world settings, and to analyze the relationship between disease duration and clinical outcomes.

Methods: The FIRST Bio study was a postmarketing surveillance study of intravenous TCZ in biologics-naive patients who had a prior inadequate response or were intolerant to ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD). Effectiveness, safety, and concomitant csDMARD administration were assessed.

Comparisons of Aluminum and Silica Elution from Various Glass Vials.

To understand the risk of particle formation in glass vials, we investigated the correlation between vial surface condition and alminum (Al) or silicon (Si) elution using various suppliers' vials with or without surface treatment. The elution of Si, which can also be an indicator of Al elution, consists of two phases; the first phase is influenced by roughness of the glass surface at the time of filling, and the second phase is dependent on the fundamental elution rate from the glass tube. When vials were filled with citrate buffer at pH 7, vials with varied surface conditions showed the most obvious differences in Al and Si elution.

[IL-6 inhibitors prevent bone loss and cartilage degeneration in rheumatoid arthritis].

Dysregulation of cytokines, including interleukin-6 (IL-6), is involved in joint destruction in rheumatoid arthritis (RA). The concentration of IL-6 is increased not only in the affected joints but also in the serum. Locally, IL-6 provides the formation of pannus through the synthesis of vascular endothelial growth factor (VEGF).

Longterm Safety and Efficacy of Subcutaneous Tocilizumab Monotherapy: Results from the 2-year Open-label Extension of the MUSASHI Study.

Objective: To evaluate the longterm safety and efficacy of subcutaneous tocilizumab (TCZ-SC) as monotherapy in patients with rheumatoid arthritis (RA).

Methods: Of 346 patients who received 24 weeks of double-blind treatment with either TCZ-SC monotherapy, 162 mg every 2 weeks (q2w); or intravenous TCZ (TCZ-IV) monotherapy, 8 mg/kg every 4 weeks; 319 patients continued to receive TCZ-SC q2w in the 84-week open-label extension (OLE) of the MUSASHI study (JAPICCTI-101117). Efficacy, safety, and immunogenicity were evaluated for all patients treated with TCZ during 108 weeks.

IL-6 signal blockade ameliorates the enhanced osteoclastogenesis and the associated joint destruction in a novel FcγRIIB-deficient rheumatoid arthritis mouse model.

Objective: We earlier found that TNFα but not interleukin (IL)-17 is indispensable in the pathogenesis of spontaneously occurring rheumatoid arthritis (RA)-like disease in our newly established FcγRIIB-deficient C57BL/6 (B6) mouse model, designated KO1. Here, we examined the role of IL-6 in the pathogenesis of RA features in KO1, with particular reference to cartilage and bone destruction in arthritic joints.

Methods: To evaluate the preventive effect of MR16-1, a rat anti-mouse IL-6 receptor (IL-6R) mAb, 4-month-old preclinical KO1 mice were divided into three groups: the first treated with MR16-1 for 6 months, the second treated with normal rat IgG, as a control, and the third left untreated.

Validation of the classification criteria for cryoglobulinaemic vasculitis.

Objective: The aim of this study was to validate the classification criteria for cryoglobulinaemic vasculitis (CV).

Methods: Twenty-three centres were involved. New patients with CV (group A) and controls, i.

Longterm safety and effectiveness of the anti-interleukin 6 receptor monoclonal antibody tocilizumab in patients with systemic juvenile idiopathic arthritis in Japan.

Objective: To assess the longterm safety and effectiveness of tocilizumab (TCZ) in systemic-onset juvenile idiopathic arthritis (sJIA).

Methods: The longterm extension phase of 2 pivotal studies (phase II with 11 patients and phase III with 56 patients) in patients with active sJIA was analyzed. Patients received open-label TCZ (8 mg/kg, every 2 weeks) without concomitant use of disease-modifying antirheumatic drugs.

Anti-interleukin-6 receptor antibody (MR16-1) promotes muscle regeneration via modulation of gene expressions in infiltrated macrophages.

Background: Although rat anti-mouse IL-6 receptor (IL-6R) antibody (MR16-1) has been reported to effectively ameliorate various tissue damages, its effect on skeletal muscle regeneration has not been determined. Moreover, the localization, persistence and duration of action of this reagent in damaged tissues after systemic administration have not been assessed.

Methods: The MR16-1 was administered i.

Retreatment efficacy and safety of tocilizumab in patients with rheumatoid arthritis in recurrence (RESTORE) study.

Objectives: To evaluate the safety and efficacy of retreatment with tocilizumab (TCZ) in patients who had participated in the DREAM study (Drug free remission/low disease activity after cessation of tocilizumab [Actemar] monotherapy study) and had experienced loss of efficacy.

Methods: Patients were retreated with TCZ or other disease modifying antirheumatic drugs (DMARDs). Disease activity was measured using the 28-joint disease activity score (DAS28) for 12 weeks.

Drug free REmission/low disease activity after cessation of tocilizumab (Actemra) Monotherapy (DREAM) study.

Objectives: To investigate the duration of remission and low disease activity (LDA) after cessation of tocilizumab (TCZ) treatment in rheumatoid arthritis patients who showed remission or LDA as assessed by DAS28 in response to preceding TCZ monotherapy, and to explore the factors contributing to prolonged efficacy duration.

Methods: Disease activity was monitored for 56 weeks. The rate of continued efficacy was estimated by Kaplan-Meier curves.

Immune response to influenza vaccine and pneumococcal polysaccharide vaccine under IL-6 signal inhibition therapy with tocilizumab.

Objectives: To evaluate humoral immune response to influenza vaccine and polysaccharide pneumococcal vaccine in patients with rheumatoid arthritis (RA) or Castleman's disease (CD) during tocilizumab therapy.

Methods: Thirty-eight patients (28 RA and 10 CD) receiving tocilizumab and 39 RA patients receiving TNF inhibitors and/or synthetic DMARDs subcutaneously received a single dose of a split-virion inactivated influenza vaccine containing A(New Caledonia (NC):H1N1), A(Hiroshima (HIR):H3N2) and B(Malaysia (MAL)) strains. Twenty-one RA patients using tocilizumab also received 23-valent polysaccharide pneumococcal vaccine.