scholarly journals The “NOMINAL” trial: Clinical efficacy, cosmetic acceptability, and local tolerability of topical 5% minoxidil lotion without propylene glycol: A 6-month, multicentre, real-life, prospective, assessor-blinded study in 196 subjects with hair loss.

2021 ◽  
Vol 9 (6) ◽  
Author(s):  
Laura Alessi ◽  
Maria Aloisi ◽  
Valentina Amadu ◽  
Alex Arena ◽  
Ylenia Balice ◽  
...  
Keyword(s):  
Clinical Response ◽  
Propylene Glycol ◽  
Scale Score ◽  
Clinical Efficacy ◽  
Real Life ◽  
Similar Response ◽  
Androgenic Alopecia ◽  
Local Tolerability ◽  
Good Tolerability ◽  
Grade Scale

Background and Trial Objectives: A new propylene glycol (PG)-free 5% minoxidil (Mnx) (PG-Free-Mnx) lotion has been recently commercialized. Clinical efficacy and local tolerability have been, so far, documented in a limited number of patients. The aim of this study was to evaluate the clinical efficacy, cosmetic acceptability, and local tolerability of 6-month application of this new PG-Free Mnx lotion in a real-life situation. Materials and Methods: The NOMINAL (NO-PG MINoxidil reAL life study) trial was performed in 22 out-patients Italian dermatology clinics. A total of 196 subjects of both sexes with a diagnosis of androgenic alopecia (AGA) and female androgenic alopecia (FAGA) were enrolled in the trial, after their written informed consent. PG-Free-Mnx lotion was applied 1 ml twice daily for 6 months. Clinical efficacy was evaluated in an open fashion in all the enrolled subjects with a 5-grade scale score (from-2: severe worsening, to +2: very good improvement in comparison with baseline condition). In a subgroup of subjects (n=60) an assessor-blinded clinical efficacy evaluation has been also performed using high definition standardized and coded scalp global pictures at baseline, and after 6 months by an assessor unaware of the temporal sequence using a 3-grade score (from 0: no improvement to 3: very high improvement). Cosmetic acceptability evaluation was assessed using a 7-item questionnaire using a 10-point scale score, with score 1 meaning not at all and score 10 meaning the worst possible condition. Cosmetic acceptability and clinical efficacy were evaluated after 12 and 24 weeks of treatment. Global tolerability, assessed at week 24, was evaluated with a 4-grade scale score (from -1: very low tolerability to +2: very good tolerability). Results: All but seven (3.6%) subjects concluded the study. Clinical efficacy scores (open evaluation) were 0.8±0.7 and 1.0±0.7 at week 12 and 24, respectively. Good or very good clinical response (score +1 or +2) at week 12 and week 24 was observed in 64% and 74% respectively of the subjects with a similar response in women (75%) and men (73%). Baseline severity of AGA/FAGA was inversely correlated with the clinical response with a better outcome in subjects with AGA type II in comparison with subjects with types III/IV AGA. The clinical efficacy was confirmed by the assessor-blinded evaluation of the subgroup of 60 subjects’ pictures at baseline (clinical score at baseline: 0.2±0.4 vs. 1.8±0.7 after 6 months; p=0.0001; absolute mean difference: 1.6; 95% CI: 1.1 to 2.0). Cosmetic acceptability score mean values were always <2 at each time-point evaluation, demonstrating good or very good acceptability. Global Tolerability score mean±SD value was 1.7±0.4 with 94% of the subjects reporting good or very good tolerability with no differences between men and women. No subjects reported severe or very severe (Tolerability score >7) burning, itching or redness sensations. Conclusions: This new PG-free lotion shows, in real-life conditions, a very good cosmetic acceptability and tolerability profile. Clinical efficacy, evaluated both in open and assessor-blinded fashions, was also documented, and it was in line with the available data of traditional Mnx formulations with propylene glycol.

SAT0416 ENTHESITIS AND CLINICAL RESPONSE IN PSORIATIC ARTHRITIS: REAL-LIFE DATA

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1161.1-1161
Author(s):  
S. Ganhão ◽  
S. Garcia ◽  
B. M. Fernandes ◽  
M. Rato ◽  
F. Pinheiro ◽  
...  
Keyword(s):  
Back Pain ◽  
Psoriatic Arthritis ◽  
Disease Activity ◽  
Clinical Response ◽  
Real Life ◽  
Inflammatory Back Pain ◽  
Skeletal Involvement ◽  
Vas Score ◽  
Das 28 ◽  
The Mean

Background:Psoriatic arthritis (PsA) is an inflammatory arthritis that is characterized by a broad spectrum of clinical conditions, including axial skeletal involvement, enthesitis, dactylitis, uveitis and arthritis. Among those, enthesitis, the inflammation of the junction where the tendon, ligament or joint capsule inserts into the bone, is assigned to be the hallmark, affecting 35–50% of patients. Several clinical methods have been developed to measure it, including The Maastricht AS Enthesitis Score (MASES) index, which tests 13 entheses and the Spondyloarthritis Research Consortium of Canada (SPARCC) index that assesses 16.Objectives:To assess the relationship between enthesitis and clinical response in psoriatic arthritis.Methods:Retrospective study including all the patients with PsA meeting the CASPAR criteria, beginning first-line biologic therapy at our centre. Demographic and clinical data including age, gender, body mass index (BMI), smoking status, physical examination findings such as presence of enthesitis, dactylitis, chronic back pain, tender and swollen joint counts (TJC/ SJC), ESR, CRP, DAS 28 4vESR, BASDAI, BASFI, BASMI, ASDAS, HAQ, patient VAS score, MASES and SPARCC were collected from the Portuguese database Reumapt. Statistical analysis was performed with SPSS. Continuous variables were analysed through Spearman correlations.Results:We included 119 patients with PsA (60 female), of which 14.9% were active smokers. The mean age of patients was 46.3 ± 1.03 years. The median disease duration was 6.8 (0.3-33.8) years and the mean BMI was 26.8 ± 0.5 Kg/m2.Enthesitis, dactylitis, inflammatory back pain, peripheral arthritis, ungueal distrophy, and psoriasis were present in 53 (45.7%), 45 (38.8%), 76 (65.5%), 109 (94%), 45 (38.8%), 104 (89.7%) patients, respectively.At baseline, mean (SD) disease activity parameters were: DAS 28 4vESR 4.9 (0.2), ESR 33.2 (2.3) mm/h; CRP 2.35 (0.3) mg/dL, HAQ 1.3 (0.1), BASDAI 6.6 (0.2), ASDAS 3.9 (0.1), BASMI 3.7 (0.2), BASFI 5.8 (0.3), MASES 1.9 (0.3), SPARCC 2.3 (0.3). Median (min-max) values of TJC, SJC and patient VAS score at baseline were 4 (0-28), 3 (0-19), 76 (0-100), respectively.There were statistically significant positive correlations (0-12 months) between ΔMASES and ΔDAS 28 4vESR (p=0.02, rho=0.432), Δpatient VAS score (p=0.027, rho=0.307), ΔHAQ (p=0.02, rho=0.411), ΔBASDAI (p=0.025, rho=0.326), ΔBASFI (p=0.037, rho=0.315), ΔASDAS (p=0.023, rho= 0.331). Correlations between ΔSPARCC and ΔDAS 28 4vESR (p=0.023, rho=0.332), Δpatient VAS score (p=0.003, rho=0.402), ΔHAQ (p=0.012, rho=0.440), ΔBASDAI (p=0.011, rho=0.368), ΔBASFI (p=0.001, rho=0.445), ΔASDAS (p=0.002, rho= 0.437), ΔCDAI (p=0.039, rho=0.320) and ΔSDAI (p=0.039, rho=0.319), were also significant. However, there weren’t strong correlations between ΔMASES neither ΔSPARCC and PsARC response at 12 months.Conclusion:Our results suggest that enthesitis is correlated with clinical response in PsA, supporting the idea that it is a major determinant of disease activity. It should be given more importance, namely by incorporating it in daily clinical practice, due to its major role, both in establishing an early diagnosis and in assessing treatment response.References:[1]Sunar I, Ataman S, Nas K, Kilic E, Sargin B, Kasman SA, et al. Enthesitis and its relationship with disease activity, functional status, and quality of life in psoriatic arthritis: a multi‑center study. Rheumatol Int. 2019 Nov 26. doi: 10.1007/s00296-019-04480-9.Disclosure of Interests:Sara Ganhão: None declared, Salomé Garcia: None declared, Bruno Miguel Fernandes: None declared, Maria Rato: None declared, Filipe Pinheiro: None declared, Eva Mariz: None declared, Miguel Bernardes Speakers bureau: Abbvie, Amgen, Biogen, Eli-Lilly, Glaxo-Smith-Kline, Pfizer, Janssen, Novartis, Lúcia Costa: None declared

scholarly journals Early epigenetic changes and DNA damage do not predict clinical response in an overlapping schedule of 5-azacytidine and entinostat in patients with myeloid malignancies

Blood ◽  
2009 ◽  
Vol 114 (13) ◽  
pp. 2764-2773 ◽  
Author(s):  
Tamer E. Fandy ◽  
James G. Herman ◽  
Patrick Kerns ◽  
Anchalee Jiemjit ◽  
Elizabeth A. Sugar ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dna Damage ◽  
Clinical Response ◽  
Clinical Efficacy ◽  
Dna Methyltransferase ◽  
Hdac Inhibitors ◽  
Hematologic Malignancies ◽  
Epigenetic Therapy ◽  
Dnmt Inhibitors ◽  
Sequential Administration

Abstract Sequential administration of DNA methyltransferase (DNMT) inhibitors and histone deacetylase (HDAC) inhibitors has demonstrated clinical efficacy in patients with hematologic malignancies. However, the mechanism behind their clinical efficacy remains controversial. In this study, the methylation dynamics of 4 TSGs (p15INK4B, CDH-1, DAPK-1, and SOCS-1) were studied in sequential bone marrow samples from 30 patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) who completed a minimum of 4 cycles of therapy with 5-azacytidine and entinostat. Reversal of promoter methylation after therapy was observed in both clinical responders and nonresponders across all genes. There was no association between clinical response and either baseline methylation or methylation reversal in the bone marrow or purified CD34+ population, nor was there an association with change in gene expression. Transient global hypomethylation was observed in samples after treatment but was not associated with clinical response. Induction of histone H3/H4 acetylation and the DNA damage–associated variant histone γ-H2AX was observed in peripheral blood samples across all dose cohorts. In conclusion, methylation reversal of candidate TSGs during cycle 1 of therapy was not predictive of clinical response to combination “epigenetic” therapy. This trial is registered with http://www.clinicaltrials.gov under NCT00101179.

scholarly journals EFFICACY OF TACROLIMUS FOR INDUCTION OF REMISSION IN PATIENTS WITH MODERATE-TO-SEVERE ULCERATIVE COLITIS: A SYSTEMATIC REVIEW AND META-ANALYSIS

2017 ◽  
Vol 54 (2) ◽  
pp. 167-172 ◽  
Author(s):  
Juan LASA ◽  
Pablo OLIVERA
Keyword(s):  
Systematic Review ◽  
Ulcerative Colitis ◽  
Clinical Response ◽  
Clinical Efficacy ◽  
Lower Risk ◽  
Meta Analysis ◽  
Calcineurin Inhibitors ◽  
Cochrane Library ◽  
Severe Ulcerative Colitis ◽  
Risk Of Failure

ABSTRACT BACKGROUND There is evidence that shows that calcineurin inhibitors may be useful for the treatment of severe ulcerative colitis. However, evidence regarding the efficacy of tacrolimus for remission induction in this setting is scarce. OBJECTIVE To develop a systematic review on the existing evidence regarding the clinical efficacy of tacrolimus for the induction of remission in patients with moderate-to-severe ulcerative colitis. METHODS A literature search was undertaken from 1966 to August 2016 using MEDLINE, Embase, LILACS and the Cochrane Library. The following MeSH terms were used: “Inflammatory Bowel Diseases” or “Ulcerative Colitis” and “Calcineurin Inhibitors” or “Tacrolimus” or “FK506”. Studies performed in adult ulcerative colitis patients that evaluated the clinical efficacy of tacrolimus for the induction of remission were considered for revision. A meta-analysis was performed with those included studies that were also placebo-controlled and randomized. Clinical response as well as clinical remission and mucosal healing were evaluated. RESULTS Overall, 755 references were identified, from which 22 studies were finally included. Only two of them were randomized, placebo-controlled trials. A total of 172 patients were evaluated. A significantly lower risk of failure in clinical response was found for tacrolimus versus placebo [RR 0.58 (0.45-0.73)]; moreover, a lower risk of failure in the induction of remission was also found versus placebo [RR 0.91 (0.82-1)]. CONCLUSION Tacrolimus seems to be a valid therapeutic alternative for the induction of remission in patients with moderate-to-severe ulcerative colitis.

scholarly journals P663 Efficacy of tofacitinib in patients with ulcerative colitis after previous ineffective biological therapies

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S545-S546
Author(s):  
M Rutka ◽  
K Farkas ◽  
D Pigniczki ◽  
K Szántó ◽  
B Anita ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Response ◽  
Induction Therapy ◽  
Dose Escalation ◽  
Real Life ◽  
Janus Kinase ◽  
Inadequate Response ◽  
Mayo Score ◽  
Number Of Patients

Abstract Background Tofacitinib (TFC) is an oral, small-molecule Janus kinase inhibitor, which was recently approved for moderate to severe ulcerative colitis (UC). The aim of the current real-life study was to determine efficacy of TFC induction therapy regarding the clinical response and remission in patients with active UC. We evaluated short-term efficacy data in a Hungarian cohort with prior exposure to other biological agents such as anti-TNF drugs and vedolizumab. Methods In this single-centre retrospective study, patients with TFC introduction were included. Since January 2019, a total of 16 patients received an oral TFC induction therapy in a dose of 10 mg twice daily for 8 weeks. Endoscopic activity was evaluated by endoscopic Mayo (eMayo) score before the introduction of TFC and in case of an inadequate therapeutic response to the 5-mg-therapy to confirm therapeutic decision-making. Based on the evaluation of clinical symptoms and laboratory parameters, we either kept the dosage or reduced the dose to 5 mg according to local regulations. We also collected data from the 16. and 24. weeks of the therapy. Primary endpoints were a clinical response (as a reduction in partial Mayo Score [pMayo] by minimum 3 points) or remission (as a Mayo score of the maximum of 2 points and without blood in stool) at week 8. Results Sixteen patients had received the induction therapy (mean age: 36 years, 7 males and 9 females) in our centre. After 8 weeks, 12 (75%) patients responded to the TFC induction therapy and 6 (37.5%) of them were in remission. Four patients were primary non-responders (25%). Corticosteroid therapy (18 ± 7 mg) was required during the induction in 4 responder cases, which could be stepped down by week 8. As a continuous maintenance therapy, 4 patients have already reached the 16th week and 8 have completed the 24th week. By the end of the follow-up, 12 patients responded and 10 was in remission. During the observation period, 3 patients had to remain on 10 mg TFC dose, 6 patients required dose escalation from 5 mg to 10 mg and 5 mg was sufficient in case of only 3 patients after the introduction. Endoscopic activity showed a moderate decrease from 2.5 ± 0.5 eMayo score to 2 ± 1 (n = 7) until week 16. In respect the responder patients, CRP levels decreased from the mean of 7.23 to 5.02. No serious side-effects were observed during the follow-up. Conclusion After the 8-week TFC induction therapy, the response rate was high and only every fourth patients were non-responder. A low number of patients had adequate reactions to the 5 mg-therapy after the introduction, but TFC is effective with dose-escalation in respect of clinical response and remission in patients with UC, who have had an inadequate response to previous biological therapy.

scholarly journals Population pharmacokinetics of dolutegravir: influence of drug–drug interactions in a real-life setting

2019 ◽  
Vol 74 (9) ◽  
pp. 2690-2697 ◽  
Author(s):  
Catalina Barcelo ◽  
Manel Aouri ◽  
Perrine Courlet ◽  
Monia Guidi ◽  
Dominique L Braun ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Plasma Concentrations ◽  
Real Life ◽  
Therapeutic Drug ◽  
Population Pharmacokinetic ◽  
Genetic Barrier ◽  
Good Tolerability ◽  
Standard Dosage ◽  
Real Life Setting ◽  
Trough Concentrations

Abstract Objectives Dolutegravir is widely prescribed owing to its potent antiviral activity, high genetic barrier and good tolerability. The aim of this study was to characterize dolutegravir’s pharmacokinetic profile and variability in a real-life setting and to identify individual factors and co-medications affecting dolutegravir disposition. Methods A population pharmacokinetic model was developed using NONMEM®. Relevant demographic factors, clinical factors and co-medications were tested as potential covariates. Simulations based on the final model served to compare expected dolutegravir concentrations under standard and alternative dosage regimens in the case of drug–drug interactions. Results A total of 620 dolutegravir plasma concentrations were collected from 521 HIV-infected individuals under steady-state conditions. A one-compartment model with first-order absorption and elimination best characterized dolutegravir pharmacokinetics. Typical dolutegravir apparent clearance (CL/F) was 0.93 L/h with 32% between-subject variability, the apparent volume of distribution was 20.2 L and the absorption rate constant was fixed to 2.24 h−1. Older age, higher body weight and current smoking were associated with higher CL/F. Atazanavir co-administration decreased dolutegravir CL/F by 38%, while darunavir modestly increased CL/F by 14%. Rifampicin co-administration showed the largest impact on CL/F. Simulations suggest that average dolutegravir trough concentrations are 63% lower after 50 mg/12h with rifampicin compared with a standard dosage of 50 mg/24h without rifampicin. Average trough concentrations after 100 mg/24h and 100 mg/12h with rifampicin are 92% and 25% lower than the standard dosage without rifampicin, respectively. Conclusions Patients co-treated with dolutegravir and rifampicin might benefit from therapeutic drug monitoring and individualized dosage increase, up to 100 mg/12 h in some cases.

scholarly journals Visual systemizing preference in children with autism: A randomized controlled trial of intranasal oxytocin

2017 ◽  
Vol 30 (2) ◽  
pp. 511-521 ◽  
Author(s):  
Lane Strathearn ◽  
Sohye Kim ◽  
D. Anthony Bastian ◽  
Jennifer Jung ◽  
Udita Iyengar ◽  
...  
Keyword(s):  
Social Communication ◽  
Controlled Trial ◽  
Real Life ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Fixation Time ◽  
Similar Response ◽  
Double Blind ◽  
Visual Preference ◽  
Control Subjects

AbstractSeveral studies have suggested that the neuropeptide oxytocin may enhance aspects of social communication in autism. Little is known, however, about its effects on nonsocial manifestations, such as restricted interests and repetitive behaviors. In the empathizing–systemizing theory of autism, social deficits are described along the continuum of empathizing ability, whereas nonsocial aspects are characterized in terms of an increased preference for patterned or rule-based systems, called systemizing. We therefore developed an automated eye-tracking task to test whether children and adolescents with autism spectrum disorder (ASD) compared to matched controls display a visual preference for more highly organized and structured (systemized) real-life images. Then, as part of a randomized, double-blind, placebo-controlled crossover study, we examined the effect of intranasal oxytocin on systemizing preferences in 16 male children with ASD, compared with 16 matched controls. Participants viewed 14 slides, each containing four related pictures (e.g., of people, animals, scenes, or objects) that differed primarily on the degree of systemizing. Visual systemizing preference was defined in terms of the fixation time and count for each image. Unlike control subjects who showed no gaze preference, individuals with ASD preferred to fixate on more highly systemized pictures. Intranasal oxytocin eliminated this preference in ASD participants, who now showed a similar response to control subjects on placebo. In contrast, control participants increased their visual preference for more systemized images after receiving oxytocin versus placebo. These results suggest that, in addition to its effects on social communication, oxytocin may play a role in some of the nonsocial manifestations of autism.

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