Real-World Evidence of Treatment with Teneligliptin/Canagliflozin Combination Tablets for Type 2 Diabetes Mellitus: A Post-Marketing Surveillance in Japan.

INTRODUCTION: Teneligliptin/canagliflozin combination tablets, which combine a dipeptidyl peptidase-4 (DPP-4) inhibitor (teneligliptin) and a sodium-glucose cotransporter 2 (SGLT2) inhibitor (canagliflozin), are a treatment option for type 2 diabetes mellitus (T2DM) in Japan. This post-marketing surveillance evaluated the real-world safety and effectiveness of teneligliptin/canagliflozin combination tablets, and changes in self-reported adherence to oral antihyperglycaemic agents. METHODS: Japanese patients with T2DM who were prescribed the combination tablets for the first time between December 2017 and June 2018 were registered and followed up for 12 months. Safety and effectiveness were assessed in terms of adverse drug reactions (ADRs) and the changes in haemoglobin A1c (HbA1c) and body weight from baseline to 12 months with the last observation carried forward, respectively. Adherence was assessed using the Morisky Medication Adherence Scale 8. RESULTS: Overall, 821 patients were eligible for the analyses, including 733 who were prescribed the combination tablets for 12 months. ADRs and serious ADRs were reported in 4.38% and 0.85% of patients, respectively. Gastrointestinal disorders (0.97%) were the most common class of ADRs. No new safety concerns were identified beyond those described in the Japanese package insert. The changes in HbA1c and body weight from baseline to 12 months were - 0.43 ± 0.93% and - 1.29 ± 5.57 kg, respectively. The reductions in HbA1c at 12 months tended to be greater among patients who switched from either DPP-4 inhibitors (- 0.71 ± 0.89%) or SGLT2 inhibitors (- 0.51 ± 1.00%) relative to patients who switched from both (- 0.22 ± 0.88%). The decrease in body weight was greatest among patients who switched from DPP-4 inhibitors. An improvement in self-reported adherence to oral antihyperglycaemic agents occurred after switching to the combination tablets. CONCLUSION: Teneligliptin/canagliflozin combination tablets were effective and associated with an improvement in adherence without new safety concerns in Japanese patients with T2DM in real-world clinical practice. TRIAL REGISTRATION: JapicCTI-173778.

Teneligliptin/canagliflozin combination tablets are used as an option for the treatment of type 2 diabetes mellitus in Japan. We performed this surveillance to obtain data on the frequency of side effects (adverse drug reactions) and effectiveness (in terms of changes in haemoglobin A1c and body weight) in Japanese patients treated with teneligliptin/canagliflozin combination tablets in real-world clinical practice. We also asked patients to evaluate their adherence to oral antihyperglycaemic agents as part of their prescribed therapies. We collected data for up to 12 months. We detected no new safety concerns, other than those already described in the Japanese package insert for the combination tablets. In terms of effectiveness, we observed improvements in both haemoglobin A1c and body weight over 12 months of treatment. Furthermore, self-reported adherence to oral antihyperglycaemic agents improved after treatment with the combination tablets.

Real-World Safety and Effectiveness of Canagliflozin Treatment for Type 2 Diabetes Mellitus in Japan: SAPPHIRE, a Long-Term, Large-Scale Post-Marketing Surveillance.

INTRODUCTION: This long-term post-marketing surveillance (SAPPHIRE) collected information on the safety and effectiveness of canagliflozin (approved dose 100 mg) prescribed to patients with type 2 diabetes mellitus (T2DM) in real-world practice in Japan. METHODS: Patients with T2DM who were prescribed canagliflozin between December 2014 and September 2016 were registered and observed for up to 3 years. Safety was evaluated in terms of adverse drug reactions (ADRs). Effectiveness was assessed in terms of glycaemic control. Data were also analysed across age subgroups (< 65, ≥ 65 to < 75, and ≥ 75 years old) and the estimated glomerular filtration rate (eGFR) categories for chronic kidney disease (G1-G5 based on eGFR) at baseline. RESULTS: A total of 12,227 patients were included in the safety analyses and 11,675 in effectiveness analyses. Overall, 7104 patients were treated with canagliflozin for ≥ 3 years. The mean age, haemoglobin A1c (HbA1c), and eGFR at baseline were 58.4 ± 12.5 years, 8.01 ± 1.49%, and 80.04 ± 21.85 mL/min/1.73 m2, respectively. There were 1836 ADRs in 1312 patients (10.73%) and 268 serious ADRs in 225 patients (1.84%). The most common ADRs were those related to volume depletion (1.39%), genital infection (1.34%), polyuria/pollakiuria (1.23%), and urinary tract infection (1.19%). The frequencies of ADRs tended to increase with age and stage of chronic kidney disease. The reductions in mean HbA1c after starting canagliflozin were maintained for up to 3 years with a mean change of - 0.68% (n = 6345 at 3 years). Maintained reductions in mean HbA1c were observed in each age subgroup and in patients with G1-G3b renal function. CONCLUSION: This surveillance in real-world clinical practice showed that canagliflozin provides sustained glucose-lowering effects in patients with T2DM, including elderly patients and patients with moderate renal impairment, without new safety concerns beyond those already described in the Japanese package insert. TRIAL REGISTRATION: JapicCTI-153048.

Canagliflozin is a sodium­glucose cotransporter 2 (SGLT2) inhibitor that lowers blood glucose levels by increasing urinary glucose excretion. It was approved for the management of blood glucose levels in patients with type 2 diabetes mellitus following clinical trials. However, clinical trials may not fully represent the safety or effectiveness of a drug in real-world clinical practice. Therefore, a 3-year post-marketing surveillance was performed in Japan to obtain safety and effectiveness data for a large group of 12,227 patients with type 2 diabetes mellitus and various demographic/clinical characteristics. Safety and effectiveness data were collected for up to 3 years while patients were treated with canagliflozin. Adverse drug reactions occurred in 10.73% of patients. The most common types of adverse drug reactions were those related to volume depletion (body fluid decreased), followed by genital infection, polyuria/pollakiuria (increased urination), and urinary tract infection. Adverse drug reactions tended to be more common in elderly patients and in patients with renal impairment. As expected, canagliflozin was associated with improvements in haemoglobin A1c, a marker of blood glucose control, in patients with type 2 diabetes, including in elderly patients and patients with moderate renal impairment. In this surveillance in real-world clinical practice, long-term treatment with canagliflozin raised no new safety concerns beyond the information already included in the Japanese package insert. Canagliflozin provides sustained glucose-lowering effects.

Patient Preference for Treatment Mode of Biologics in Rheumatoid Arthritis: A 2020 Web-based Survey in Japan.

INTRODUCTION: Although the proportion of patients with rheumatoid arthritis (RA) using biologic disease-modifying antirheumatic drugs (bDMARDs) has increased steadily, the relationship between patient background and preference for bDMARDs has not been fully investigated. METHODS: We conducted a web-based questionnaire survey among patients aged ≥ 20 years with RA receiving bDMARDs. Participants were recruited through an internet research company in Japan. Study endpoints included factors affecting the preferred bDMARD treatment mode, namely, in-hospital intravenous infusion (infusion), in-hospital subcutaneous injection (in-hospital injection), or self-administered subcutaneous injection (self-injection), and discrepancies between the current and preferred treatment mode. RESULTS: Of the 400 patients surveyed for preferred treatment mode, 15.3% preferred infusion, 18.0% preferred in-hospital injection, and 66.8% preferred self-injection. A preference for infusion (odds ratio [OR] 2.218 and 6.165) and in-hospital injection (OR 4.735 and 6.026) versus self-injection was significantly associated with higher current frequency of hospital visits and anxiety or other hurdles related to self-injection. A flexible administration setting was significantly associated with a preference for self-injection versus infusion (OR 0.401) and versus in-hospital injection (OR 0.445). Further, age (< 40 vs. ≥ 60 years) was significantly associated with a preference for self-injection versus in-hospital injection (OR 0.120). Many patients reported no discrepancy between their current and preferred treatment mode (patients receiving infusion, 68.0%; in-hospital injection, 71.2%; and self-injection, 94.0%). However, > 90% of patients responded that they would change their current mode in the future following a recommendation by a medical professional, aging, or a change in RA symptoms. CONCLUSIONS: This web-based survey showed that patient preference for bDMARD treatment mode was significantly associated with age, frequency of hospital visits, flexible administration setting, and anxiety or other hurdles to self-injection. Changes in patient background which affect the preferred treatment mode should be considered in decision-making for RA therapy with bDMARDs. TRIAL REGISTRATION: R000048089 (UMIN-CTR).

Dose Adjustment of Methotrexate Administered Concomitantly with Golimumab for Rheumatoid Arthritis in Japanese Real-World Clinical Settings.

INTRODUCTION: The combination of methotrexate (MTX) with biological disease-modifying antirheumatic drugs (bDMARDs) is a recommended treatment option for rheumatoid arthritis (RA) patients showing an inadequate response to MTX monotherapy. However, the adequate dose of MTX, especially in long-term treatment with bDMARDs/MTX combination therapy, remains under-addressed. Since RA patients require long-term treatment, we examined the effects of using golimumab (GLM) in the long run as well as its persistency and associated factors. METHODS: We used the Japan Medical Data Center Inc. (JMDC) administrative claims data of 489 patients receiving GLM therapy for calculating the persistency in patients with constant, reduced, or escalated MTX dosing. The factors associated with GLM persistency were assessed using Cox proportional hazard modeling, controlling for the dose adjustment of concomitant MTX, age, sex, RA disease period, and the initial dose of GLM or concomitant MTX during GLM/MTX combination therapy. RESULTS: During GLM/MTX combination therapy, up to 52% of patients were reported to experience dose adjustments of concomitant MTX treatment (i.e., dose reduction and escalation in 34% and 18% of patients, respectively). Persistency was similar in the MTX dose-reduction patients and the MTX dose-constant patients. In the Cox proportional hazard model, no significant differences were observed in association with GLM persistency, including with respect to MTX dose adjustment. CONCLUSIONS: GLM prescription was continued in 80% or more (1 year) and 50% or more (3 years) of RA patients receiving reduced concomitant MTX dosing, suggesting that MTX dose adjustment (including MTX reduction) could be considered in GLM/MTX combination therapy.