Effectiveness and safety of subcutaneous abatacept in biologic-naïve RA patients at Week 52: A Japanese multicentre investigational study (ORIGAMI study).

OBJECTIVES: To evaluate the effectiveness and safety of abatacept over 52 weeks in biologic-naïve rheumatoid arthritis (RA) patients with moderate disease activity in the prospective, 5-year, observational study (ORIGAMI study) in Japan. METHODS: Abatacept (125 mg) was administered subcutaneously once a week. Clinical outcomes included Simplified Disease Activity Index (SDAI) remission at Week 52 (primary endpoint), Japanese Health Assessment Questionnaire (J-HAQ), EuroQol 5-Dimension Questionnaire (EQ-5D), treatment retention, and safety. The results were compared with those of conventional synthetic disease-modifying antirheumatic drug (csDMARD) controls from the ongoing Institute of Rheumatology, Rheumatoid Arthritis (IORRA) registry. RESULTS: Overall, 325 patients were enrolled, with a mean age of 66.9 ± 12.7 years. The proportion of patients achieving SDAI remission (≤3.3) at Week 52 was 18.9% (95% CI: 14.3-23.6) and low disease activity (≤11) was 53.3% (95% CI: 47.4-59.1). A significant improvement was observed in J-HAQ and EQ-5D over 52 weeks in both the abatacept and csDMARD groups. The probability of abatacept treatment retention at Week 52 was 69.9% (95% CI: 64.7-75.5). Adverse events and serious adverse events were reported in 50.0% and 12.1% of patients, respectively. CONCLUSIONS: Abatacept significantly improved disease activity, physical disability, and quality of life for up to 52 weeks in RA patients in a real-world setting.

Long-term safety and efficacy of weekly subcutaneous tocilizumab monotherapy in patients with rheumatoid arthritis who had an inadequate response to subcutaneous tocilizumab every other week: Results from the open-label extension of the SHINOBI study.

Objective: To evaluate the long-term safety and efficacy of subcutaneous tocilizumab (TCZ-SC) monotherapy administered weekly (qw) in patients with rheumatoid arthritis who had an inadequate response to TCZ-SC every other week (q2w). Methods: Patients who completed 12 weeks of double-blind treatment with either TCZ-SC q2w monotherapy or TCZ-SC qw monotherapy were switched to or continued to receive open-label treatment with TCZ-SC qw monotherapy for 40 weeks. Safety and efficacy were assessed. Subgroup analyses of Disease Activity Score based on 28 joints using erythrocyte sedimentation rate (DAS28-ESR) were performed at 12 weeks. Results: The incidence of adverse events was 464.4/100 patient-years (PY). The incidence of infection was 121.3/100 PY. The safety profile of TCZ-SC qw monotherapy was consistent with that of prior studies of TCZ. No additional safety concerns were observed. Improvement from baseline in DAS28-ESR was maintained at week 52 in patients who continued TCZ-SC qw and improved in patients who switched from TCZ-SC q2w to qw. At week 12, the efficacy of TCZ-SC qw monotherapy was greater than that of TCZ-SC q2w monotherapy irrespective of weight and BMI subgroups. Conclusion: The long-term weekly dosing of TCZ-SC monotherapy was well tolerated and efficacy was maintained over 52 weeks.

A randomized, double-blind, parallel-group, phase III study of shortening the dosing interval of subcutaneous tocilizumab monotherapy in patients with rheumatoid arthritis and an inadequate response to subcutaneous tocilizumab every other week: Results of the 12-week double-blind period.

OBJECTIVE: To determine the efficacy and safety of subcutaneous tocilizumab (TCZ-SC) monotherapy every week (qw) versus every other week (q2w) in patients with rheumatoid arthritis who had an inadequate response to TCZ-SC q2w. METHODS: Adult patients in Japan with inadequate response to TCZ-SC q2w were randomized to either TCZ-SC 162 mg qw monotherapy or TCZ-SC 162 mg q2w monotherapy for 12 weeks (double-blind). The primary endpoint was the change from baseline in adjusted Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) at week 12. Efficacy, safety and pharmacokinetics were assessed. RESULTS: TCZ-SC qw was superior to TCZ-SC q2w for adjusted mean change in DAS28-ESR from baseline to week 12. The difference in the change in DAS28-ESR between TCZ-SC qw and q2w was -1.21 (95%CI: -2.13, -0.30, p = .0108). A higher proportion of patients receiving TCZ-SC qw achieved DAS28-ESR remission/low disease activity than TCZ-SC q2w. Adverse events were 71.4% and 66.7% for TCZ-SC qw and q2w, respectively; infection was the most common event with one fatal case with TCZ-SC qw. CONCLUSIONS: In patients with inadequate response to TCZ-SC q2w, shortening the dosing interval to qw improved efficacy with acceptable tolerability. Occurrence of infection for both TCZ q2w and qw is important and needs careful attention.

The efficacy of mizoribine for the treatment of rheumatoid arthritis and its correlation with renal function.

OBJECTIVES: To evaluate the correlation between the efficacy of mizoribine (MZR) and the factors that might effect MZR concentration: renal function and dosage and administration of MZR in patients with rheumatoid arthritis (RA). METHODS: The efficacy of MZR treatment was prospectively evaluated in 97 RA regardless of dosage, at the 14 participated institutions. The Disease Activity Score 28-CRP3 was used to assess RA activity. The renal function was evaluated based on the serum creatinine and serum cystatin-C (Cys-C). The patients were followed up for 24 weeks. RESULTS: The patients with a mean age 66.2 years included 18 male. The renal function assessment showed increased creatinine in 16.4% of patients and increased Cys-C in 54.5%, suggesting the higher sensitivity of Cys-C to detect impaired renal function than creatinine. In patients with good or moderate response according to the European League against Rheumatism classification criteria, the Cys-C was significantly higher compared with those with no response. MZR treatment was significantly more effective in patients with an arithmetic product of the single MZR dose used and Cys-C of 179 or more. CONCLUSIONS: The efficacy of MZR may increase in proportion to its single dose, or increased Cys-C level in patients with impaired renal function.

Clinical characteristics and risk factors for Pneumocystis jirovecii pneumonia in patients with rheumatoid arthritis receiving adalimumab: a retrospective review and case-control study of 17 patients.

OBJECTIVES: To investigate the clinical characteristics and risk factors of Pneumocystis jirovecii pneumonia (PCP) in rheumatoid arthritis (RA) patients treated with adalimumab. METHODS: We conducted a multicenter, retrospective, case-control study to compare RA patients treated with adalimumab with and without PCP. Data from 17 RA patients who were diagnosed with PCP and from 89 RA patients who did not develop PCP during adalimumab treatment were collected. RESULTS: For the PCP patients, the median age was 68 years old, with a median RA disease duration of eight years. The median length of time from the first adalimumab injection to the development of PCP was 12 weeks. At the onset of PCP, the median dosages of prednisolone and methotrexate were 5.0 mg/day and 8.0 mg/week, respectively. The patients with PCP were significantly older (p < 0.05) and had more structural changes (p < 0.05) than the patients without PCP. Computed tomography of the chest revealed ground-glass opacity without interlobular septal boundaries in the majority of the patients with PCP. Three PCP patients died. CONCLUSIONS: PCP may occur early in the course of adalimumab therapy in patients with RA. Careful monitoring, early diagnosis, and proper management are mandatory to secure a good prognosis for these patients.

Multibacterial sepsis in an alcohol abuser with hepatic cirrhosis.

An alcohol abuser with hepatitis C developed multibacterial sepsis. His mean 100% alcohol intake reached 400 ml/day. In January 2001, he suddenly experienced fever (39 degrees C) with no other symptoms. One week later, he was admitted to our hospital and was subsequently diagnosed with sepsis associated with four species of bacteria (Streptococcus constellatus, Fusobacterium mortiferum, Bacteroides thetaiotaomicron, and non-spore-forming anaerobic gram-positive bacillus). A drip infusion of imipenem/cilastatin was administrated, resulting in a successful therapeutic outcome. No underlying disorder was found except for gastric ulcers and hepatic cirrhosis. Damaged gastric mucosa was assumed to be the possible cause and route for the bacterial invasion.