This 12-week study evaluated the efficacy and safety of capsaicin 8% patch versus placebo patch in painful diabetic peripheral neuropathy (PDPN). Patients aged 18 years or older with PDPN were ...randomized (1:1) to one 30-minute treatment (capsaicin 8% patch or placebo patch) to painful areas of the feet. Overall, 369 patients were randomized (capsaicin 8% patch, n = 186; placebo patch, n = 183). Percentage reduction in average daily pain score from baseline to between weeks 2 through 8 (the primary end point) was statistically significant for capsaicin 8% patch versus placebo (−27.4% vs −20.9%; P = .025); improvements in pain were observed from week 2 onward. Versus placebo, patients treated with capsaicin 8% patch had a shorter median time to treatment response (19 vs 72 days) and modest improvements in sleep interference scores from baseline to between weeks 2 through 8 (P = .030) and weeks 2 through 12 (P = .020). Apart from application site reactions, treatment-emergent adverse events were similar between groups. No indications of deterioration in sensory perception of sharp, cold, warm, or vibration stimuli were observed. In patients with PDPN, capsaicin 8% patch treatment provided modest pain relief and sleep quality improvements versus a placebo patch, similar in magnitude to other treatments with known efficacy, but without systemic side effects or sensory deterioration.
To our knowledge, this is the first study of the capsaicin 8% patch versus placebo in patients with PDPN to show that one 30-minute capsaicin treatment provides modest improvements in pain and sleep quality. Results confirm the clinical utility of the capsaicin 8% patch in the diabetic population.
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•Capsaicin 8% patch provided effective relief in painful diabetic peripheral neuropathy.•Improvements in sleep quality were modest and significant with capsaicin 8% patch.•Capsaicin 8% patch was well tolerated with no deterioration in sensory perception.•Safety and tolerability were in line with previous studies of capsaicin 8% patch.
Recurrent Clostridioides (Clostridium) difficile infection (rCDI) is common and increases healthcare resource utilization. In this study, we assessed rCDI risk factors using an up-to-date, Japanese ...national hospital-based database.
C. difficile infection (CDI) episodes, occurring July 2014–June 2017, in patients aged ≥18 years were extracted from the database and a nested case-control analysis was performed. Cases were defined as rCDI episodes which required re-initiation of oral vancomycin or oral/intravenous metronidazole treatment within 8 weeks from the start of initial treatment. Cases were matched to 4 non-rCDI episodes at the timing of rCDI occurrence. Adjusted odds ratios (ORs) were estimated using multivariate conditional logistic regression model.
Of 18,246 initial CDI episodes, 3250 (17.8%) had at least one rCDI. Approximately 90% of episodes occurred in inpatients and 65% were treated with metronidazole. Older age (<75 years vs 75–84 years and vs 85 + years) was associated with higher risk of rCDI (OR = 1.27, 95% confidence interval 1.15, 1.41 and 1.45 1.30, 1.61, respectively). Use of systemic antibiotics (3.16 2.90, 3.44), probiotics (2.53 2.32, 2.77), chemotherapy (1.28 1.08, 1.53), or proton pump inhibitors (PPIs) (1.17 1.07, 1.28), and prior CDI history (1.22 1.03, 1.43) were also identified as rCDI risk factors. Vancomycin reduced the risk of rCDI compared with metronidazole treatment (0.83 0.76, 0.91).
This large, multicenter, nationwide study confirmed that older age, PPIs, antibiotics, probiotics, chemotherapy, and prior CDI history are risk factors for rCDI in Japan. There was a 17% decrease of rCDI risk with vancomycin vs metronidazole treatment.
Clinical trial registration number: N/A.
This 52-week study evaluated the long-term safety and tolerability of capsaicin 8% w/w (179 mg) patch repeat treatment plus standard of care (SOC) versus SOC alone in painful diabetic peripheral ...neuropathy (PDPN).
Phase 3, multinational, open-label, randomised, controlled, 52-week safety study, conducted in Europe. Patients were randomised to capsaicin 8% patch repeat treatment (30 or 60 min; 1-7 treatments with ≥ 8-week intervals) to painful areas of the feet plus SOC, or SOC alone. The primary objective was the safety of capsaicin 8% patch repeat treatment (30 min and 60 min applications) plus SOC versus SOC alone over 52 weeks, assessed by changes in Norfolk Quality of Life-Diabetic Neuropathy (QOL-DN) total score from baseline to end of study (EOS). Secondary safety endpoints included Utah Early Neuropathy Scale (UENS) assessments and standardised testing of sensory perception and reflex function.
Overall, 468 patients were randomised (30 min plus SOC, n = 156; 60 min plus SOC, n = 157; SOC alone, n = 155). By EoS, mean changes in Norfolk QOL-DN total score from baseline estimated mean difference versus SOC alone; 90% CI for difference were: 30 min plus SOC, -27.6% -20.9; -31.7, -10.1; 60 min plus SOC, -32.8% -26.1; -36.8, -15.4; SOC alone, -6.7%. Mean changes difference versus SOC alone in UENS total score by EoS versus baseline were: 30 min plus SOC, -2.1 -0.9; -1.8, 0.1; 60 min plus SOC, -3.0 -1.7; -2.7, -0.8; SOC alone, -1.2. No detrimental deterioration was observed in any of the Norfolk or UENS subscales by EoS with capsaicin. Also, no worsening in sensory perception testing of sharp, warm, cold and vibration stimuli was found with capsaicin by EoS. Capsaicin treatment was well tolerated and the most frequent treatment-emergent adverse events were application site pain (30 min, 28.2%; 60 min, 29.3%), burning sensation (30 min, 9.0%; 60 min, 9.6%) and application site erythema (30 min, 7.7%; 60 min, 8.9%).
In patients with PDPN, capsaicin 8% patch repeat treatment plus SOC over 52 weeks was well tolerated with no negative functional or neurological effects compared with SOC alone.
ClinicalTrials.gov registration: NCT01478607 . Date of registration November 21, 2011; retrospectively registered.
This analysis of the RASH trial (NCT01729481) aimed at gaining a better understanding of the "Burden of Therapy" (BOTh
) in pancreatic ductal adenocarcinoma (PDAC). In the RASH study, 150 patients ...with newly diagnosed metastatic PDAC were treated with gemcitabine plus erlotinib (gem/erlotinib) for four weeks. Patients who developed a skin rash during this four-week run-in phase continued with the gem/erlotinib treatment, while rash-negative patients were switched to FOLFIRINOX. The study demonstrated a 1-year survival rate of rash-positive patients who received gem/erlotinib as first-line treatment that was comparable to previous reports of patients receiving FOLFIRINOX. To understand whether these comparable survival rates may be accompanied by better tolerability of the gem/erlotinib treatment compared to FOLFIRINOX, the BOTh
methodology was used to continuously quantify and depict the burden of therapy generated by treatment emergent events (TEAEs). Sensory neuropathy was significantly more common in the FOLFIRINOX arm, and prevalence as well as severity increased over time. In both arms, the BOTh
associated with diarrhea decreased over the course of treatment. The BOTh
caused by neutropenia was comparable in both arms but decreased in the FOLFIRINOX arm over time, possibly due to chemotherapy dose reductions. Overall, gem/erlotinib was associated with a slightly higher overall BOTh
, but the difference was not statistically significant (
= 0.6735). In summary, the BOTh
analysis facilitates the evaluation of TEAEs. In patients fit for intense chemotherapeutic regimens, FOLFIRINOX is associated with a lower BOTh
than gem/erlotinib.
Although early intervention for chronic kidney disease (CKD) and renal anemia are desirable, these conditions are often asymptomatic during their early stages and may be underdiagnosed.
We ...retrospectively analyzed Japanese administrative claims data for general and hospital populations. The data period for the general and hospital data ranged from January 2011 to December 2016 and from April 2008 to July 2017, respectively. CKD stage was determined by estimated glomerular filtration rate (eGFR). Anemia was defined per Japanese guidelines using hemoglobin (Hb) values. The proportion of patients who had eGFR-defined stages G3–G5 CKD without a CKD diagnosis, and Hb-defined anemia without an anemia diagnosis or treatment records, was estimated.
Among 16,779 (general) and 68,161 (hospital) patients, a high proportion of G3 CKD patients did not have a CKD-related diagnosis (general: G3a, 95.0%; G3b, 68.4%; hospital: G3a, 89.2%; G3b, 67.9%); however, some patients were treated with antihypertensives. Among anemic patients, 75.7% (G3a) and 66.7% (G3b) of the general population, and 56.2% (G3a) and 47.5% (G3b) of the hospital population, did not have an anemia-related diagnosis or treatment. CKD and anemia were more likely to be diagnosed in patients with G4 and G5 CKD.
A high proportion of G3 CKD patients did not have a CKD-related diagnosis. Likewise, many anemic patients with G3 CKD did not have an anemia-related diagnosis. Despite the lack of a CKD-related diagnosis, some patients received appropriate treatment (e.g., antihypertensives). Further outreach to CKD and anemia patients at earlier stages may be warranted.
The emergence of urinary retention (UR), specifically acute urinary retention (AUR), has been a concern when treating men with lower urinary tract symptoms (LUTS) with antimuscarinic drugs.
In ...NEPTUNE (12-week, double-blind), men (≥45 years) with LUTS were randomized to receive tamsulosin oral-controlled absorption system (TOCAS) 0.4 mg, fixed-dose combination (FDC) of solifenacin (Soli) 6 mg + TOCAS 0.4 mg, FDC Soli 9 mg + TOCAS 0.4 mg, or placebo. In NEPTUNE II (40-week, open-label extension of NEPTUNE), continuing patients received 4-week FDC Soli 6 mg + TOCAS, then FDC Soli 6 mg or 9 mg + TOCAS for the remainder of the study, switchable every 3 months.
Across both studies, 1208 men received ≥1 dose of FDC Soli 6 mg or 9 mg + TOCAS for up to 52 weeks; 1199 men completed NEPTUNE and 1066 received ≥1 dose in NEPTUNE II. In total, 13 men (1.1%; 95% CI, 0.6%-1.8%) reported a UR event while receiving FDC, eight of which were AUR (0.7%; 95% CI, 0.3%-1.3%, incidence 7/1000 man-years). Six men reported UR events while taking Soli 6 mg + TOCAS (three AUR), and seven men reported a UR event while taking Soli 9 mg + TOCAS (five AUR). One man developed AUR while taking TOCAS alone and four reported UR (three AUR) during placebo run-in. Most AUR/UR events occurred within 4 months of treatment initiation.
FDC Soli and TOCAS was associated with a low rate of UR and AUR in men with LUTS.
Abstract Background Patient-level data are available for 11 randomized, controlled, Phase III/Phase IV solifenacin clinical trials. Methods Meta-analyses were conducted to interrogate the data, to ...broaden knowledge about solifenacin and overactive bladder (OAB) in general. Before integrating data, datasets from individual studies were mapped to a single format using methodology developed by the Clinical Data Interchange Standards Consortium (CDISC). Initially, the data structure was harmonized, to ensure identical categorization, using the CDISC Study Data Tabulation Model (SDTM). To allow for patient level meta-analysis, data were integrated and mapped to analysis datasets. Mapping included adding derived and categorical variables and followed standards described as the Analysis Data Model (ADaM). Mapping to both SDTM and ADaM was performed twice by two independent programming teams, results compared, and inconsistencies corrected in the final output. ADaM analysis sets included assignments of patients to the Safety Analysis Set and the Full Analysis Set. Results There were three analysis groupings: Analysis group 1 (placebo-controlled, monotherapy, fixed-dose studies, n = 3011); Analysis group 2 (placebo-controlled, monotherapy, pooled, fixed- and flexible-dose, n = 5379); Analysis group 3 (all solifenacin monotherapy-treated patients, n = 6539). Treatment groups were: solifenacin 5 mg fixed dose, solifenacin 5/10 mg flexible dose, solifenacin 10 mg fixed dose and overall solifenacin. Patient were similar enough for data pooling to be acceptable. Conclusions Creating ADaM datasets provided significant information about individual studies and the derivation decisions made in each study; validated ADaM datasets now exist for medical history, efficacy and AEs. Results from these meta-analyses were similar over time.
ABSTRACT
Objectives
There is limited information on the clinical use of Janus kinase inhibitors (JAKis) for rheumatoid arthritis treatment in Japan. The aim of this study was to identify ...disease-modifying antirheumatic drug (DMARD) treatment patterns in Japan.
Methods
This retrospective, longitudinal study extracted data from the Japan Medical Data Center database. Patients with rheumatoid arthritis diagnosis were enrolled 2016–19, during which patients had a first prescription of a major DMARD, split into six mutually exclusive classes: methotrexate (MTX); other conventional synthetic DMARDs; tumour necrosis factor alpha inhibitors; cytotoxic T-lymphocyte-associated antigen-4-immunoglobulin; anti-interleukin-6 receptor therapies; and JAKis. The primary objective was to describe DMARD treatment patterns, especially for JAKis.
Results
Overall, 10,399 patients were included in the analysis. The most common treatments were MTX, other conventional synthetic DMARDs, and tumour necrosis factor alpha inhibitors. The total number of JAKi prescriptions increased approximately 8-fold during 2016–19. Most (61.1%) patients who received JAKis had prior MTX or tumour necrosis factor alpha inhibitor treatment. The duration of JAKi treatment was longer than for biologics and other conventional synthetic DMARDs and comparable to that of MTX.
Conclusions
The sequence of drug class prescriptions for rheumatoid arthritis in Japan during 2016–19 followed clinical guidelines. Over this period, JAKis were increasingly used as a second-line treatment following MTX.
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