The Impact of ANxA6 Gene Polymorphism on the Efficacy of Methotrexate Treatment in Psoriasis Patients

Dermatology ◽  
2021 ◽  
pp. 1-9
Author(s):  
Zhijia Fan ◽  
Zhenghua Zhang ◽  
Qiong Huang ◽  
Ling Han ◽  
Xu Fang ◽  
...  

<b><i>Background:</i></b> There are great interindividual variations in the clinical efficacy of methotrexate (MTX) treatment and patients’ genetic background seems promising in its explanation. <b><i>Objectives:</i></b> The study aimed to test whether the polymorphism of annexin A6 (ANxA6) gene, a susceptibility factor for psoriasis, was associated with the clinical response to MTX therapy. <b><i>Methods:</i></b> A total of 325 patients enrolled in the study received oral MTX treatment, of whom 310 completed the 1-year study and performed the genotype analysis. They were defined as responders (a reduction of Psoriasis Area and Severity Index [PASI] score ≥75%) and nonresponders (a reduction of PASI &#x3c;50%) compared to baseline after 12 weeks of short-time therapy. On 1-year treatment, they were defined as responders if they achieved PASI75 and absolute PASI ≤3, otherwise as nonresponders. The genotypes of 4 single-nucleotide polymorphisms (SNPs) in the ANxA6 gene were verified using the Sequenom platform. Potential predictors associated with the treatment outcome of MTX were assessed by binary logistic regression. <b><i>Results:</i></b> We found significant associations for the ANxA6 SNPs of rs11960458, rs960709, and rs13168551 with psoriasis severity. Patients with rs11960458 CC genotype and rs960709 GG genotype showed higher percentages of PASI75 and improvement rates of PASI at 12 weeks. And on 1-year treatment, statistical difference occurred in rs11960458 rather than other SNPs compared between responders and nonresponders that the frequency of CC genotype was higher in responders (<i>p</i> = 0.019). After adjustment for potential confounders, patients with rs11960458 TT/CT genotype (at 12 weeks: OR 0.483, 95% CI 0.245–0.951, <i>p</i> = 0.035; at 1 year: OR 0.483, 95% CI 0.280–0.833, <i>p</i> = 0.009) were significantly more likely to not respond to MTX both on the short-term and long-term treatment, while rs960709 and rs13168551 polymorphisms were only associated with the short-term efficacy of MTX (<i>p</i> = 0.018 and <i>p</i> = 0.036, respectively). <b><i>Conclusions:</i></b> The CC ge­notype of ANxA6 (rs11960458) was significantly associated with a better response when compared to those patients with the TT/CT genotype, thus being a potential predictor for the clinical efficacy of MTX.

Author(s):  
Manjiri Walinjkar ◽  
P.D. Londhe ◽  
S. R. Makhare ◽  
Anil Avhad

Background: Shvitra (vitiligo) is a kind of skin disorder comprising of white coloured skin patches which is considered as a social stigma. Worldwide prevalence of Vitiligo is observed as 1% of the total population. Due to the chronic nature, long term treatment, lack of uniform effective therapy and unpredictable course the disease is usually very demoralizing for patients. Aim: To study the efficacy of ‘Dhatryadi Ghanavati’ in the management of Shvitra. Materials and Methods: Total 50 patients of Shvitra from OPD and IPD unit of Dr. M.N. Agashe Hospital, Satara were selected and provided with Dhatryadi Ghanavati 1gm B.D. for the duration of 3 months. Results: 100% relief was observed in Daha and Kandu followed by 83.33% relief was observed in Rukshata. 34.51% improvement was seen in number of patches, 34.82% in size of patches and 34.29% in percentage area involved. Color of the patches was improved by 69.01% whereas 44% improvement was seen in hair discoloration. Conclusion: The compound formulation ‘Dhatryadi Ghanavati’ was found as an effective remedy for ‘Shvitra’. The parameters like number of patches, size of patches, percentage area involved and colour of patches showed statistically highly significant results.


2004 ◽  
Vol 16 (6) ◽  
pp. 319-325 ◽  
Author(s):  
Pierre S. Chue ◽  
Peter D'Hoore ◽  
J. Michael Ramstack

Chronic disorders such as schizophrenia require long-term treatment programs in order to maintain patients at the lowest level of symptomatology, reduce the likelihood of psychotic relapse, and support achievement of remission and recovery. Evidence suggests that treatment with long-acting injectable antipsychotics reduces the impact of partial compliance and provides predictable release of medication, assuring continuous therapeutic coverage. Until recently, only conventional antipsychotic agents were available in long-acting formulations, thereby foregoing the advantages of the atypical class. Atypical agents which are given orally have been shown to provide long-term efficacy and tolerability benefits compared with conventional agents, but are limited by the need for daily administration. The most recent pharmacological strategy to achieve optimal maintenance treatment has been to combine the benefits of an atypical antipsychotic with delivery in a water-based long-acting formulation. The first antipsychotic to achieve this combination – long-acting risperidone – may thus represent an important advance in the optimization of long-term treatment outcomes in patients with schizophrenia.


2021 ◽  
pp. 112067212110523
Author(s):  
Martin Stattin ◽  
Anna-Maria Haas ◽  
Daniel Ahmed ◽  
Alexandra Graf ◽  
Katharina Krepler ◽  
...  

Purpose A model was calculated during the first Austrian coronavirus disease-2019 (COVID-19) pandemic lockdown to estimate the effect of a short-term treatment interruption due to healthcare restrictions on visual acuity (VA) in neovascular age-related macular degeneration (nAMD). The model was compared to the real-life outcomes before treatment re-started. Methods Retrospective data-collection of 142 eyes in 142 patients receiving repeated intravitreal injections with anti-VEGF at a retina unit in Vienna in a personalized pro-re-nata regimen prior to the COVID-19 associated lockdown, when treatment was deferred between March 16 and May 4, 2020. During the lockdown, the preliminary data was integrated into pre-existing formulae based on the natural course of the disease in untreated eyes in the long term. Patients were re-scheduled and treated after gradually opening operating rooms. The calculation model was compared to the effective VA change. Results The model calculated an overall VA loss of 3.5 ± 0.8 letters early treatment diabetes retinopathy study (ETDRS) ( p < 0.001 [95% CI:3.3;3.6]) on average compared to 2.5 ± 6 letters ETDRS ( p < 0.001 [95% CI:1.5;3.5]) as measured with a mean treatment delay of 61 ± 14 days after previously scheduled appointments. The total difference between the model exercise and the real-life outcomes accounted for 1 ± 5.9 letters ETDRS ( p = 0.051 [95% CI: 0.1;1.9]). Conclusion The herein presented calculation model might not be suitable to estimate the effective VA loss correctly over time, although untreated eyes and eyes under therapy show similarities after short-term treatment interruption. However, this study demonstrated the potentially negative impact of the COVID-19 pandemic lockdown on patients compromised by nAMD.


CNS Spectrums ◽  
1998 ◽  
Vol 3 (9) ◽  
pp. 64-71 ◽  
Author(s):  
Gary A. Christenson ◽  
Scott J. Crow ◽  
James E. Mitchell ◽  
Thomas B. Mackenzie ◽  
Ross D. Crosby ◽  
...  

AbstractThis short-term, open-label study investigates short- and long-term effects of the selective serotonin reuptake inhibitor (SSRI) fluvoxamine for the treatment of trichotillomania (TTM). Additionally, this study aimed to test the hypothesis that the presence of hair pulling compulsiveness is predictive of SSRI response. Nineteen subjects meeting the Diagnostic and Statistical Manual of Mental Disorders, Third Edition Revised, (DSM-III-R) criteria for TTM were treated with fluvoxamine at doses up to 300 mg/day. Random regression analysis of change across time for patients who completed the study (n=14) and those who dropped out (n=5) revealed statistically significant improvements in Physician Rating Scale, hair-pulling episodes, Trichotillomania Impairment Scale, and Trichotillomania Symptom Severity Scale, but not in estimated amount of hair pulled. In addition, the percentage of patients' focused or compulsive hair-pulling symptoms was predictive of treatment response. Unfortunately, all three subjects who entered long-term treatment displayed substantial movement back toward baseline by the end of 6 months. We concluded that fluvoxamine produces moderate reductions in symptoms during the short-term treatment of TTM and that the presence of focused or compulsive hair pulling may be predictive of treatment response. However, responses may be short lived when treatment is extended.


Spine ◽  
2006 ◽  
Vol 31 (26) ◽  
pp. 3061-3069 ◽  
Author(s):  
Steven J. Atlas ◽  
Yuchiao Chang ◽  
Robert B. Keller ◽  
Daniel E. Singer ◽  
Yen A. Wu ◽  
...  

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1259
Author(s):  
Gerard Anmella ◽  
Silvia Vilches ◽  
Jordi Espadaler ◽  
Andrea Murru ◽  
Isabella Pacchiarotti ◽  
...  

Several pharmacogenetic-based decision support tools for psychoactive medication selection are available. However, the scientific evidence of the gene-drug pairs analyzed is mainly based on pharmacogenetic studies in patients with major depression or schizophrenia, and their clinical utility is mostly assessed in major depression. This study aimed at evaluating the impact of individual genes, with pharmacogenetic relevance in other psychiatric conditions, in the response to treatment in bipolar depression. Seventy-six patients diagnosed with bipolar disorder and an index major depressive episode were included in an observational retrospective study. Sociodemographic and clinical data were collected, and all patients were genotyped using a commercial multigene pharmacogenomic-based tool (Neuropharmagen®, AB-Biotics S.A., Barcelona, Spain). Multiple linear regression was used to identify pharmacogenetic and clinical predictors of efficacy and tolerability of medications. The pharmacogenetic variables response to serotonin-norepinephrine reuptake inhibitors (SNRIs) (ABCB1) and reduced metabolism of quetiapine (CYP3A4) predicted patient response to these medications, respectively. ABCB1 was also linked to the tolerability of SNRIs. An mTOR-related multigenic predictor was also associated with a lower number of adverse effects when including switch and autolytical ideation. Our results suggest that the predictors identified could be useful to guide the pharmacological treatment in bipolar disorder. Additional clinical studies are necessary to confirm these findings.


2020 ◽  
Author(s):  
Daniel S. Helman

Schizophrenia is a major mental illness with a disease course that is influenced by lifestyle. The risk-benefit ratio for alternative interventions is more favorable than for antipsychotics in long-term treatment. Dietary interventions may target autoimmune features, vitamin or mineral deficiencies, abnormal lipid metabolism, gluten sensitivity or others. Examples of interventions involving diet, physical activity or physical processes, or social interventions including talk therapy exist in the literature. Notwithstanding, the general utility of these types of interventions remains inconclusive, awaiting long-term randomized trials. A perspective that separates the cause of the disease from its symptoms may be helpful in treatment planning and is warranted to distinguish between short-term and long-term recovery goals.


2020 ◽  
Vol 15 (2) ◽  
pp. 110-124
Author(s):  
Joy E. Ikekpeazu ◽  
Oliver C. Orji ◽  
Ikenna K. Uchendu ◽  
Lawrence U.S. Ezeanyika

Background and Objective: There may be a possible link between the use of HAART and oxidative stress-related mitochondrial dysfunction in HIV patients. We evaluated the mitochondrial and oxidative impacts of short and long-term administration of HAART on HIV patients attending the Enugu State University Teaching (ESUT) Hospital, Enugu, Nigeria following short and long-term therapy. Methods: 96 patients categorized into four groups of 24 individuals were recruited for the study. Group 1 comprised of age-matched, apparently healthy, sero-negative individuals (the No HIV group); group 2 consisted of HIV sero-positive individuals who had not started any form of treatment (the Treatment naïve group). Individuals in group 3 were known HIV patients on HAART for less than one year (Short-term treatment group), while group 4 comprised of HIV patients on HAART for more than one year (Long-term treatment group). All patients were aged between 18 to 60 years and attended the HIV clinic at the time of the study. Determination of total antioxidant status (TAS in nmol/l), malondialdehyde (MDA in mmol/l), CD4+ count in cells/μl, and genomic studies were all done using standard operative procedures. Results: We found that the long-term treatment group had significantly raised the levels of MDA, as well as significantly diminished TAS compared to the Short-term treatment and No HIV groups (P<0.05). In addition, there was significantly elevated variation in the copy number of mitochondrial genes (mtDNA: D-loop, ATPase 8, TRNALEU uur) in the long-term treatment group. Interpretation and Conclusion: Long-term treatment with HAART increases oxidative stress and causes mitochondrial alterations in HIV patients.


2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
J. Newcomer ◽  
R. Ratner ◽  
M. Åström ◽  
H. Eriksson

Background:Data pertaining to changes in weight during long-term treatment with quetiapine (QTP) have been published previously (1).Methods:Pooled data are presented from 26 short-term clinical studies (up to 12 weeks) of QTP or quetiapine extended-release (QTP XR)-as monotherapy or adjunct therapy-conducted by AstraZeneca up to November 2007. Studies were conducted in adult patients (18-65 years) across a number of psychiatric diagnoses. Variables were analyzed irrespective of fasting status with similar analyses planned in the fasting subset. LSM changes from baseline for the difference between QTP and placebo are presented.Results:Approximately 10000 patients were included in the analyses, 70% of whom were treated with QTP or QTP XR. Across the entire short-term dataset, the difference in LSM change in weight for QTP vs. placebo was 1.07 kg. Corresponding differences in glucose regulation parameters were 1.39 mg/dL for glucose and 0.04% units for HbA1C. the overall difference in total cholesterol was 5.48 mg/dL, with differences in HDL and LDL cholesterol of -0.62 mg/dL and 1.69 mg/dL. the difference in LSM change in triglycerides was 22.62 mg/dL.Discussion:Within the context of balancing potential risks against the acknowledged benefits of atypical antipsychotics, the degree and significance of variations in metabolic parameters is an area of continued interest. This analysis helps clinicians to better understand changes in important metabolic parameters across trials with QTP and QTP XR, and the size and uniqueness of the dataset permits further analyses within this important area.Supported by funding from AstraZeneca Pharmaceuticals LP.


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