In patients with rheumatoid arthritis, tofacitinib was associated with greater reductions in signs and symptoms than methotrexate. Herpes zoster infections and increases in creatinine and in LDL and ...HDL cholesterol levels were more common with tofacitinib.
Rheumatoid arthritis is a chronic autoimmune disease characterized by inflammation and by joint destruction that leads to substantial disability. The predominant first-line treatment is methotrexate, a nonbiologic agent that is associated with acceptable clinical and functional improvements. Although methotrexate prevents progressive joint damage in some patients,
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–
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concerns have been raised regarding its side effects and safety.
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–
8
In one study, discontinuation of methotrexate was reported after 2 years of treatment in one third of the patients and after 5 years of treatment in more than half the patients.
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In combination with methotrexate, biologic disease-modifying antirheumatic drugs (DMARDs), including tumor . . .
Crisaborole ointment 2% is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate atopic dermatitis (AD). The mechanism of action of crisaborole and its effects on ...lesional measures of disease severity are not yet well defined.
This phase 2a, single-center, vehicle-controlled, intrapatient study was designed to further characterize the mechanism of action of crisaborole through evaluation of clinical efficacy and changes in skin biomarkers in adults (n = 40) with mild-to-moderate AD.
Two target lesions were randomized in an intrapatient (1:1) manner to double-blind crisaborole/vehicle applied twice daily for 14 days. Patients then applied crisaborole (open-label) to all affected areas for 28 days. Punch biopsy specimens were collected for biomarker analysis at baseline, day 8 (optional), and day 15.
Crisaborole treatment resulted in early improvement in lesional signs/symptoms versus vehicle, with improvement in pruritus (pruritus numeric rating scale) observed as early as 24 hours after the first application. Crisaborole-treated lesions showed significant percentage improvement from baseline in lesional transcriptomic profile compared with vehicle at day 8 (91.15% vs 36.02%, P < 10−15) that was sustained until day 15 (92.90% vs 49.59%, P < 10−15). Crisaborole significantly modulated key AD biomarkers versus vehicle, including TH2 and TH17/TH22 pathways and epidermal hyperplasia/proliferation. Molecular profiles and epidermal pathology normalized toward nonlesional skin and correlated with clinical changes in lesion severity and barrier function.
Crisaborole reversed biomarker profiles of skin inflammation and barrier function, with associated improvements in clinical efficacy measures, highlighting the therapeutic utility of targeting phosphodiesterase 4 in patients with AD.
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Objectives
The aim of this phase 3, double-blind study was to compare the radiographic and clinical effects of etanercept (ETN) versus methotrexate (MTX) over 52 weeks in Japanese subjects with ...active rheumatoid arthritis.
Methods
The study population comprised 550 subjects with inadequate response to ≥1 disease-modifying anti-rheumatic drugs who were randomized to treatment groups of ETN 25 mg twice weekly (BIW;
n
= 182), ETN 10 mg BIW (
n
= 192), or MTX (≤8.0 mg/week;
n
= 176).
Results
Of the 550 subjects initially enrolled in the three treatment groups, 21.6 % discontinued the study; a significantly higher proportion of those who withdrew from the study due to lack of efficacy were in the MTX (21.6 %) group compared with the ETN 25 mg (3.3 %) and ETN 10 mg (6.8 %) groups (
P
< 0.001). Mean change from baseline in the modified total Sharp score at week 52 (primary endpoint) was significantly lower in the ETN 25 mg 3.33; standard error (SE), 0.73 and ETN 10 mg (5.19; SE 0.93) groups than in the MTX group (9.82; SE 1.16;
P
< 0.0001 vs. either ETN group). Compared with subjects receiving MTX, significantly higher percentages of subjects treated with ETN 25 and 10 mg achieved American College of Rheumatology (ACR) ACR20 and ACR50 response rates at all time points (
P
< 0.01). ETN was well-tolerated, with no unexpected safety findings.
Conclusions
ETN 25 mg BIW and ETN 10 mg BIW slowed radiographic progression and improved clinical outcomes more effectively than MTX in this Japanese population.
Introduction
Using data from three clinical trials, the effect of crisaborole treatment on sleep outcomes for pediatric patients with atopic dermatitis (AD) and their families was examined.
Methods
...This analysis comprised patients aged 2 to < 16 years from the double-blind phase 3 CrisADe CORE 1 (NCT02118766) and CORE 2 (NCT02118792) studies, families of patients aged 2 to < 18 years from CORE 1 and CORE 2, and patients aged 3 months to < 2 years from the open-label phase 4 CrisADe CARE 1 study (NCT03356977), all with mild-to-moderate AD who received crisaborole ointment 2% twice daily for 28 days. Sleep outcomes were assessed via the Children’s Dermatology Life Quality Index and Dermatitis Family Impact questionnaires in CORE 1 and CORE 2 and the Patient-Oriented Eczema Measure questionnaire in CARE 1.
Results
In CORE 1 and CORE 2, a significantly lower proportion of crisaborole-treated patients than vehicle-treated patients reported sleep disruption at day 29 (48.5% versus 57.7%,
p
= 0.001). The proportion of families whose sleep was affected by their child’s AD in the preceding week was also significantly lower in the crisaborole group (35.8% versus 43.1%,
p
= 0.02) at day 29. At day 29 in CARE 1, the proportion of crisaborole-treated patients who experienced ≥ 1 night of disturbed sleep in the previous week decreased by 32.1% from baseline.
Conclusion
These results suggest that crisaborole improves sleep outcomes in pediatric patients with mild-to-moderate AD and their families.
Plain Language Summary
Atopic dermatitis (AD), also known as eczema, is a chronic skin disease that causes red or flaky skin patches that can become infected and itch. Children with AD often experience sleep disturbance, including difficulty falling asleep, restless sleep, waking up more frequently, and daytime drowsiness. Problems with sleep quality negatively impact children with AD, as well as their caregivers. Crisaborole ointment is applied to the skin and has been shown to improve the symptoms of AD in children and adults. This study examined how treatment with crisaborole affected sleep quality for children and their caregivers in three clinical trials. Children in these studies took crisaborole for 28 days. Researchers found that crisaborole treatment improved sleep in children with mild-to-moderate AD and their caregivers. This was determined using four measures. First, a smaller proportion of children who were treated with crisaborole experienced sleep disruption compared with those to whom a vehicle was applied (an ointment with no drug). Second, a smaller proportion of caregivers of children with AD who were treated with crisaborole reported effects on their sleep, compared with children to whom a vehicle was applied. Third, a smaller proportion of children with AD who were treated with crisaborole, as well as their caregivers, had ≥ 1 night per week of disturbed sleep after treatment compared with before treatment. Fourth, the caregivers of children treated with crisaborole reported significantly less exhaustion and tiredness because of the child’s AD. These results suggest that treatment with crisaborole improves sleep outcomes in children with mild-to-moderate AD and their caregivers.
Background:
Research on opioid-free anesthesia has increased in recent years; however, it has never been determined whether it is more beneficial than opioid anesthesia. This meta-analysis was ...primarily used to assess the effect of opioid-free anesthesia compared with opioid anesthesia on the incidence of postoperative nausea and vomiting.
Methods:
We searched the electronic databases of PubMed, the Cochrane Library, Web of Science and Embase from 2014 to 2022 to identify relevant articles and extract relevant data. The incidence of postoperative nausea and vomiting, time to extubation, pain score at 24 hours postoperatively, and time to first postoperative rescue analgesia were compared between patients receiving opioid-free anesthesia and those receiving standard opioid anesthesia. Differences in the incidence of postoperative nausea and vomiting were evaluated using risk ratios (95% confidence interval CI). The significance of the differences was assessed using mean differences and 95% CI. The heterogeneity of the subject trials was evaluated using the
I
2
test. Statistical analysis was performed using the RevMan 5.4 software.
Results:
Fourteen randomized controlled trials, including 1354 participants, were evaluated in the meta-analysis. As seen in the forest plot, the OFA group had a lower risk of postoperative nausea and vomiting than the control group (risk ratios = 0.41, 95% CI: 0.33–0.51,
P
< .00001; n = 1354), and the meta-analysis also found that the OFA group had lower postoperative analgesia scores at 24 hours (
P
< .000001), but time to extubation (
P
= .14) and first postoperative resuscitation analgesia time (
P
< .54) were not significantly different.
Conclusions:
Opioid-free anesthesia reduces the incidence of postoperative nausea and vomiting while providing adequate analgesia without interfering with postoperative awakening.
Objective
To explore the correlation between intraoperative burst suppression (BS) and postoperative delirium (POD) in elderly patients, and provide more ideas for reducing POD in clinical.
Methods
...Ninety patients, aged over 60 years, who underwent lumbar internal fixation surgery in our hospital were selected. General information of patients was obtained and informed consent was signed during preoperative visits. Patients were divided into burst suppression (BS) group and non-burst suppression (NBS) group by intraoperative electroencephalogram monitoring. Intraoperative systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and heart rate (HR) were recorded, and the variation and minimum value were obtained by calculating. Hemoglobin (HGB), C-reactive protein (CRP), system immune inflammatory index (SII) at 24 and 72 h after surgery, the incidence of postoperative adverse reactions, postoperative hospital stay, and total cost were recorded after operation. POD assessment was performed using CAM within 7 days after surgery or until discharge. SPSS25.0 was used for statistical analysis.
Results
Compared with the NBS group, the number of elderly patients with high frailty level in BS group was more (
P
= 0.048). There is correlation between BS and POD (OR: 4.954, 95%CI 1.034–23.736,
P
= 0.045), and most of the POD patients in BS group behave as hyperactive type.
Conclusion
The occurrence of intraoperative BS is associated with POD, and elderly patients with frailty are more likely to have intraoperative BS. BS can be used as a predictor of POD.
Background
Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate atopic dermatitis (AD).
Objectives
The aim of this study was to evaluate the ...safety, effectiveness, and pharmacokinetics (PK) of crisaborole in infants aged 3 to < 24 months with mild-to-moderate AD in an open-label study.
Methods
Infants (3 to < 24 months) with Investigator’s Static Global Assessment (ISGA) of mild (2) or moderate (3) and percentage of treatable body surface area (%BSA) ≥ 5 received crisaborole twice daily for 28 days; a cohort with moderate AD per ISGA and %BSA ≥ 35 were included in a PK analysis. Endpoints included safety (primary), efficacy, and PK (exploratory).
Results
Included were 137 infants total (mean age SD, 13.6 months 6.42), with 21 in the PK cohort (12.7 months 6.58). Treatment-emergent adverse events (TEAEs) were reported for 88 (64.2%) patients (98.9% rated as mild/moderate). TEAEs were considered treatment-related for 22 patients (16.1%); most frequently reported were application site pain (3.6%), application site discomfort (2.9%), and erythema (2.9%). ISGA clear/almost clear with ≥ 2-grade improvement at day 29 was achieved by 30.2% of patients. From baseline to day 29, mean percentage change in Eczema Area and Severity Index score was − 57.5%, and mean change in Patient-Oriented Eczema Measure total score was − 8.5. Crisaborole systemic exposures in infants were characterized and, based on nonlinear regression analysis, were comparable with that in patients aged ≥ 2 years.
Conclusions
In this open-label study, crisaborole was well tolerated and effective in infants (3 to < 24 months) with mild-to-moderate AD with systemic exposures similar to patients aged ≥ 2 years.
Clinical Trial Registration
NCT03356977.
Plain Language Summary
Atopic dermatitis (AD) is a skin disease that causes inflamed and itchy skin. Crisaborole is an ointment that is approved to treat patients aged 2 years and older with mild-to-moderate AD. This clinical trial studied crisaborole in infants with mild-to-moderate AD who were 3 to under 24 months old. These infants were treated with crisaborole twice a day for 28 days. The trial studied crisaborole’s safety, effectiveness, and absorption into the bloodstream. In total, 137 infants were treated. Although side effects of some sort occurred in about two-thirds of patients, only 1 in 6 patients experienced side effects that were attributed to crisaborole. When these side effects did occur, these were mainly pain, discomfort, or redness where crisaborole was applied. Fewer than 1 in 25 patients experienced each side effect where crisaborole was applied. The doctors saw improvement in the AD symptoms of some patients at day 29 of the study compared to the beginning of the study. Crisaborole blood-level measurements in this age group were consistent with those seen in patients aged 2 years and older. Overall, crisaborole was considered well tolerated and effective in infants (3 to under 24 months old) with mild-to-moderate AD.
Video abstract
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Safety, Effectiveness, and Pharmacokinetics of Crisaborole in Infants Aged 3 to < 24 Months with Mild-to-Moderate Atopic Dermatitis: An Open-Label, Phase 4 Study (MP4 40891 MB)
Background. Cognitive dysfunction after total knee arthroplasty (TKA) is very common in elderly patients. Postoperative cognitive dysfunction (POCD), as a form of cognitive dysfunction, may affect ...patients’ short- and long-term recoveries. The identification of meaningful risk factors may help reduce the occurrence of POCD in the future. Objective. Our goal was to retrospectively investigate the risk factors for early POCD in elderly patients undergoing TKA and to further analyze the relationship between the intensity of risk factors and the level of cognitive function. Methods. The related indicators and the Montreal Cognitive Function Assessment Scale (MOCA) scores of 105 elderly patients were collected by searching the electronic case system. According to the postoperative MOCA score, patients were divided into three groups: normal group (group N), mild POCD group (group M), and severe POCD group (group S). SPSS 25.0 software was used for statistical analyses. Results. At baseline, the preoperative MOCA score was significantly different in patients with POCD (P≤0.001), while other baseline indicators were not significantly different. In terms of changes in hemoglobin levels, statistically significant differences were observed between group M, group S, and group N (P=0.039). Among inflammatory indicators, only postoperative CRP levels showed a statistically significant difference in patients with POCD (P=0.041). Postoperative pain was also significantly different among the three groups (P=0.009). The multivariate regression analysis revealed that a low preoperative MOCA score and severe postoperative pain were independent risk factors for mild and severe cognitive impairment, while a high postoperative CRP level was only an independent risk factor for mild cognitive impairment. Conclusions. Our study found that the level of preoperative cognitive function, postoperative CRP level, and postoperative pain were independent risk factors for POCD. Moreover, the levels of preoperative cognitive function and postoperative pain were more strongly correlated with severe POCD than postoperative CRP levels.
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