Methotrexate pharmacogenetics in the treatment of rheumatoid arthritis

2019 ◽  
Vol 20 (17) ◽  
pp. 1235-1245 ◽  
Author(s):  
Biljana Jekic ◽  
Nela Maksimovic ◽  
Tatjana Damnjanovic
Keyword(s):  
Rheumatoid Arthritis ◽  
Molecular Basis ◽  
Therapeutic Response ◽  
Short Review ◽  
Therapy Outcomes ◽  
Therapy Failure ◽  
Drug Of Choice ◽  
Number Of Patients ◽  
Study Results

For many decades, methotrexate (MXT) has remained the drug of choice in the treatment of rheumatoid arthritis (RA). Unfortunately, a considerable number of patients do not achieve an appropriate therapeutic response. Pharmacogenetics studies do not give usable results regarding differences in MTX response among RA patients. The mechanism of MTX action in RA is not completely understood. We present and discuss data regarding the molecular basis of folate and adenosine pathways, the most obvious MTX targets, to explain possible causes of therapy failure. The molecular basis of the disease could also have an impact on therapy outcomes and in this review we explore this. Finally, we make a short review of available pharmacogenetics study results.

Ixekizumab in the Management of Non-Selected Out Patients with Moderate to Severe Psoriasis -New Data and Personal Clinical Experience

2018 ◽  
Vol 3 (3) ◽  
Keyword(s):  
Clinical Experience ◽  
Personal Experience ◽  
Therapeutic Response ◽  
Systemic Disease ◽  
Severe Psoriasis ◽  
Adequate Treatment ◽  
Scalp Psoriasis ◽  
Number Of Patients ◽  
Genital Psoriasis

Introduction: Too many patients with moderate to severe psoriasis do not receive adequate treatment. This means a vast undersupply in the treatment of patients with psoriasis. Only biologics fulfill the whole range of the treatment of psoriasis – psoriasis does not affect only skin but the whole organism: It is a systemic disease! Between the biologics are evident differences concerning the effect. Discussion: Based on broad personal experience in the management of patients with moderate to severe psoriasis new data from clinical studies with ixekizumab are examined. This contains new data on long-term-efficacy of ixekizumab, effectiveness in special localizations (scalp psoriasis, nail psoriasis, palmoplantar psoriasis, genital psoriasis) as well as safely data and experience on patients switched to ixekizumab from other biologics. Personal clinical experience is based on >300 non-selected outpatients with moderate to severe psoriasis, >250 patients on biological therapies, > 50 patients with ixekizumab. Conclusions: Focusing on a relevant number of patients switched from secukinumab to ixekizumab due to first or secondary loss of efficacy significant differences between both IL-17A-inhibitors mainly in terms of efficacy and speed of therapeutic response are shown. Finally the correlation between PASI-90-/PASI-100 response and significant changes in DLQI are highlighted.

scholarly journals AB0713 EVALUATION OF THE EFFECTIVENESS OF LASER THERAPY IN THE TREATMENT OF RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1388.1-1388
Author(s):  
N. Zhuravleva ◽  
L. Karzakova ◽  
S. Kudryashov ◽  
E. Petrova
Keyword(s):  
Rheumatoid Arthritis ◽  
Laser Therapy ◽  
Medical Therapy ◽  
Joint Pain ◽  
Morning Stiffness ◽  
Activity Index ◽  
Clinical Indicators ◽  
On Demand ◽  
Number Of Patients ◽  
Basic Medical

Background:Despite the fact that the introduction of biological disease-modifying antirheumatic medicines (bDMARDs) and the early start of treatment for rheumatoid arthritis (RA) can effectively stop the inflammatory process in RA, a fairly large number of patients continue to experience joint pain [1]. It is assumed that in some cases, joint pain in patients with RA is not associated with the inflammation, so it requires consideration of the possibility of using alternative strategies for the treatment of RA.Objectives:The aim of the research is to study the effectiveness of laser therapy in the treatment of RA.Methods:114 patients with RA aged from 32 to 53 years have been monitored for 6 months. There were 82 women (71.9 %) and 32 men (28.1%) among them. The patients were randomly divided into 2 groups. The first group of patients (57 people) received basic medical therapy with methotrexate 15 mg intramuscularly once a week and nonsteroidal anti-inflammatory medicines (NSAIDs) on demand. The dose of methotrexate was selected taking into account the disease activity index DAS 28. The second group of patients (57 people) received basic medical therapy with methotrexate 15 mg intramuscularly once a week and NSAIDs on demand. In addition, the cutaneous low-intensity laser irradiation of the joints was added along the projection of the joint gap in a pulse mode with a wavelength of 0.89 microns. The pulse frequency is 80-1500 Hz, the pulse power is 5 W, the exposure time in the field is 1-2 minutes and the total radiation time per session is no more than 10 minutes [2]. The course of treatment consisted of 10 procedures (the device “Milta F-8 RD”, Russia, Moscow). The course of laser therapy was repeated after 4 weeks. To assess clinical indicators, patients were examined using the SF-36 questionnaire before treatment and 6 months after the start of treatment.Results:The survey after 6 months revealed the significant decrease in the severity of pain on the VAS from the initial average indicator 4.5±0.2 to 3.69±0.2 points (p<0.01) and morning stiffness from 60±5 to 40.8±4 minutes (p<0.01). In the first group, the dynamics of clinical indicators were not statistically significant: the intensity of pain decreased from 4.6±0.2 to 4.2±0.3 points (p>0.05) and the duration of morning stiffness reduced from 62±7 to 58.6±6 minutes (p>0.05). In the second group the decrease in the need for NSAIDs was observed in 21 patients, while in the first group the same was observed only in 10 patients (px2 = 0.020).Conclusion:Laser therapy in the treatment of patients with RA enabled to decrease the frequency of the need for NSAIDs and reduce morning stiffness. We recommend using laser therapy in patients with RA at the second radiological stage as an addition to basic therapy.References:[1]Altawil R et al. Arthritis Care Res (Hoboken). 2016; 68(8): 1061-1068.[2]Burger M et al. Physiother Theory Pract. 2017; 33(3): 184-197.Disclosure of Interests:None declared

scholarly journals AB0135 A VERY EARLY CLINICAL RESPONSE TO TOFACITINIB IS ASSOCIATED WITH LOW RHEUMATOID ARTHRITIS ACTIVITY AFTER 3 AND 6 MONTHS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1095.3-1096
Author(s):  
A. Karateev ◽  
A. Lila ◽  
E. Nasonov ◽  
V. Mazurov ◽  
D. Chakieva ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Response ◽  
Central Sensitization ◽  
Intracellular Signaling ◽  
Pain Reduction ◽  
Pain Severity ◽  
Jak Inhibitors ◽  
Significant Pain ◽  
Number Of Patients ◽  
Days Of Therapy

Background:JAK inhibitors block intracellular signaling pathways responsible for the synthesis of cytokines and mediators involved in the development of chronic pain and central sensitization (CS). This determines a very rapid clinical response to JAK inhibitors. However, it is not clear how the significant pain reduction in the first weeks of therapy is associated with the achievement of low rheumatoid arthritis (RA) activity.Objectives:to assess the relationship between the early clinical response to tofacitinib and the decrease in RA activity after 3 and 6 months.Methods:Study group included 88 patients with RA, their age was 53±11,5, 79.3% of women, 89.8% of RF “+”, DAS28 5.2±1.2, receiving DMARDs (methotrexate 59.5% and leflunomide 19.8%), who were administered with tofacitinib 5 mg 2 times a day due to inefficacy or intolerance of biological DMARDs. There were assessed the pain severity using Brief pain inventory (BPI) questionnaire, the presence of neuropathic pain component (NPC) using PainDETECT questionnaire and signs of CS using Central Sensitisation Inventory (CSI) questionnaire at early time after tofacitinib administration, RA activity using DAS28 after 3 and 6 months.Results:The mean pain severity at baseline was 5.3±2.0 according to the visual analogue scale (VAS 0-10), 51.1% of patients had signs of central sensitization (CSI ≥ 40), 15.9% had NPC (PainDETECT ≥18). 7 days after tofacitinib intake there was statistically reliable reduction of pain severity – up to 4.1±1.8 (р<0.05) and CS – CSI from 40.4±13.5 to 36.5±12.5 (р=0.01). After 28 days, the effect was higher: the pain level (VAS) was 2.8±1.6 (p=0.000), PainDETECT decreased from 11.8±5.6 to 6.8±3.1 (p=0.000), CSI – to 31.6±13.9 (p=0.000). DAS28 after 3 and 6 months was 3.7±1.3 and 3.6±1.2. The number of patients with pain decrease of ≥50% after 28 days of therapy was 59.9%. Low RA activity after 3 months. (DAS28 ≤3.2) was achieved in 64.4% of patients. There was a clear correlation between the number of patients with significant pain reduction at 28 days and the number of patients with low RA activity after 3 and 6 months (rS=0.548, p=0.000; rS=0.790, p=0.000). Six patients withdrew from the study due to inefficacy or social reasons. There were no serious adverse reactions.Conclusion:The application of JAK inhibitor tofacitinib allows to reach a fast analgesic effect and reduce CS signs. An early clinical response to tofacitinib (pain relief) predicts a decrease in RA activity after 3 and 6 months of the therapy.Limitation: Open-label observatory study.Disclosure of Interests:None declared

scholarly journals Epidemiology of Secondary Warm Autoimmune Haemolytic Anaemia—A Systematic Review and Meta-Analysis

2021 ◽  
Vol 10 (6) ◽  
pp. 1244
Author(s):  
Stinne Tranekær ◽  
Dennis Lund Hansen ◽  
Henrik Frederiksen
Keyword(s):  
Haemolytic Anaemia ◽  
Lupus Erythematosus ◽  
Meta Analysis ◽  
Underlying Disease ◽  
Age At Diagnosis ◽  
Autoimmune Haemolytic Anaemia ◽  
Sex Distribution ◽  
Number Of Patients ◽  
Study Results ◽  
Full Text Review

Background: Warm autoimmune haemolytic anaemia (wAIHA) is a haemolytic disorder, most commonly seen among adults and is classified as either primary or secondary to an underlying disease. We describe the age and sex distribution and the proportion of secondary wAIHA. Method: We retrieved 2635 published articles, screened abstracts and titles, and identified 27 articles eligible for full-text review. From these studies, we extracted data regarding number of patients, sex distribution, age at diagnosis, number of patients with secondary wAIHA, and whether the patients were diagnosed through local or referral centres. All data were weighted according to the number of included patients in each study. Results: 27 studies including a total of 4311 patients with wAIHA, of which 66% were females, were included. The median age at diagnosis was 68.7 years, however, wAIHA affected all ages. The mean proportion of secondary wAIHA was 49%, most frequently secondary to systemic lupus erythematosus. The proportions of secondary wAIHA reported from primary vs. referral centres were 35% vs. 59%, respectively. Conclusion: This review consolidates previously reported gender distribution. The higher proportion of secondary wAIHA in referral centres suggests that the most severely affected patients are disproportionally more frequent in such facilities.

scholarly journals Assessment of Lacrimal Duct Patency in Patients Undergoing Endoscopic Medial Maxillectomy

2021 ◽  
Vol 10 (2) ◽  
pp. 245
Author(s):  
Andrzej Sieśkiewicz ◽  
Tomasz Łysoń ◽  
Marek Rogowski ◽  
Marek Bielecki ◽  
Ewa Gindzienska-Sieskiewicz ◽  
...  
Keyword(s):  
Assessment Method ◽  
Test Results ◽  
Functional Disorders ◽  
Lacrimal Duct ◽  
Assessment Tests ◽  
Number Of Patients ◽  
Study Results ◽  
Assessment Techniques ◽  
Medial Maxillectomy ◽  
Comparison Of The Results

Purpose: The risk of epiphora after medial maxillectomy with lacrimal duct transection is difficult to assess. The data available in the literature are inconclusive due to various operating techniques used by the authors of medical publications, different additional procedures aimed at improving tear drainage after maxillectomy, and a variety of lacrimal duct patency assessment techniques. The aim of our work was to assess the anatomical and functional patency of lacrimal ducts after medial maxillectomy without performing additional procedures to improve tear drainage as well as comparison of the results obtained with different assessment tests. Materials and methods: 21 patients who underwent medial maxillectomy in the years 2016–2019 were assessed for discomfort and epiphora based on patients’ own reports and basic clinical examination, lacrimal duct rinse test, the Munk score, and a modified endoscopic Jones I test. Results: Gradually increasing the sensitivity of the assessment method resulted in an increase in the number of patients with potential tear drainage disorders, starting from 0% in the rinsing test, 4.8% self-reported tearing complaints, 14.3% Munk score, and 19% modified endoscopic Jones I test. Conclusions: The study results revealed that a small fraction of patients tend to report epiphora as a consequence of medial maxillectomy themselves. Subtle functional disorders, which are not particularly bothersome to patients, are more common. More sensitive lacrimal duct patency tests reveal more cases of tear drainage disorders. The results of studies assessing the incidence of epiphora after medial maxillectomy appear to depend on the type of test used.

scholarly journals AB0237 INFECTIONS IN PATIENTS WITH RHEUMATOID ARTHRITIS TREATED WITH RITUXIMAB AND ANTI-TNF INHIBITOR

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1144.2-1144
Author(s):  
N. Zehraoui ◽  
R. Benaziez.Boutaleb ◽  
H. Hafirassou ◽  
F. Mechid ◽  
N. Bahaz ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Best Practice ◽  
Biological Therapy ◽  
Patient Characteristics ◽  
Inadequate Response ◽  
Tnf Inhibitor ◽  
Clinical Rheumatology ◽  
Number Of Patients ◽  
Serious Infections ◽  
Comparative Risk

Background:Biological therapies have significantly improved the management of rheumatoid arthritis (RA). These molecules are very effective, but are known for their specific risks, especially infectious. It depends on several factors including the type of molecule used.Objectives:The objective of our study is to compare the rate of infection in RA patients treated with rituximab and anti-TNFα.Methods:Prospective, observational, monocentric study. Were included RA patients (ACR / EULAR 2010 criteria) treated with rituximab and anti-TNFα (adalimumab, infliximab and Etanercept) after inadequate response to DMARDs.Demographic characteristics, comorbidities, association with methotrexate and corticosteroids were collected and compared for each group.The number, type and severity of the infections in both cases were noted.SPSS (Statistical Package for Social Science) was used for data analysis.Results:40 RA patients treated with rituximab and 31 patients who received anti-TNFα were included.Patient characteristics and Comparison of rate of infection in RA patients between the two groups are summarized in Table 1Table 1.ParametersRituximabAnti-TNFαpNumber of patients4031Average age (years)56,2846,060,01Sexratio0,140,110,7Average duration of evolution (years)15,8313,740,3Patients under corticosteroid (%)97,587,10,08Average corticosteroid dose6,415,480,3patients under methotrexate (%)37,545,20,5Diabetes (%)2016,10,7Patients with infection (%)32,551,60,1Number of infections18240,4Number of serious infections500,04Conclusion:The rate of infections in patients with RA treated with rituximab or anti-TNF was similar. However, the infections observed were more serious in patients with RA treated with rituximabReferences:[1]Fabiola Atzeni MD PhD and al. Infections and Biological Therapy in Patients with Rheumatic Diseases. IMAJ . VOL 18. march-APRIL 2016.[2]Huifeng Yun and al. Comparative Risk of Hospitalized Infection Associated with Biologic Agents in Rheumatoid Arthritis Patients Enrolled in Medicare. ARTHRITIS & RHEUMATOLOGY. Vol. 68, No. 1, January 2016, pp 56–66.[3]Manjari Lahiri and al. Risk of infection with biologic antirheumatic therapies in patients with rheumatoid arthritis. Best Practice & Research Clinical Rheumatology (2015) 1-16.Disclosure of Interests:None declared

scholarly journals FRI0550 CAN CYTOKINE GENE POLYMORPHISMS BE USEFUL FOR THE THERAPEUTIC CHOICE IN JAPANESE PATIENTS WITH RHEUMATOID ARTHRITIS?

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 876.2-877
Author(s):  
S. Tsujimoto ◽  
M. Shigesaka ◽  
A. Tanaka ◽  
Y. Ozaki ◽  
T. Ito ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Autoimmune Disease ◽  
Gene Polymorphisms ◽  
Therapeutic Response ◽  
Bone Erosion ◽  
Japanese Patients ◽  
Cartilage Degradation ◽  
Cytokine Gene ◽  
Biological Dmards ◽  
Cytokine Gene Polymorphisms

Background:Rheumatoid arthritis (RA) is a common autoimmune disease. It is characterized by systemic synovitis with bone erosion and joint cartilage degradation(1). Production of autoantibody is important for autoimmune disease. Cytokines play crucial roles in its pathogenesis(2). SNP distribution varies between races. Few studies have examined SNP targeted at Japanese patients. The analysis of cytokine gene polymorphisms is important factor of pathophysiology and treatment.Objectives:This analysis was aimed to investigate the association between cytokine gene polymorphisms and autoantibody and therapeutic response in Japanese RA patients.Methods:This study subjects consisted of 100 RA patients and 50 healthy controls. We extracted data on patient sex, age, disease duration, rheumatoid factor (RF), anti cyclic citrullinated peptide (anti-CCP) antibody and therapeutic response including methotrexate (MTX) and biological DMARDs. Genomic DNA was isolated from peripheral blood, these were genotyped for TNFα, TGFβ1, IL-6, IL-10 and IFNγ polymorphisms. We analyzed these data using a chi-square test.Results:IL-10 (-819 C/T and -592 C/A) revealed that there were significant decrease in the frequency of IL-10 (-819) CC genotype and (-592) CC genotype as compared to controls in RA patients. Genotyping of IL-10 showed that there was significant decrease ACC/ACC genotype (Table 1).IFNγ (+874 A/T) revealed that there was significant decrease in the frequency of TT genotype as compared to controls (Table 1).No significant differences in TNFα, TGFβ1and IL-6 genotypes and alleles frequency were observed between RA patients and control.TGFβ1(+869 A/T) in patients with anti-CCP antibody positive revealed that there was significant decrease in the frequency of TT genotype as compared to patients with anti-CCP antibody negative (Table 2).No significant association between RF and any cytokine gene polymorphism.Analyzing cytokine gene polymorphisms could be useful for treatment with MTX and biological DMARDs.Table 1.Table 2.Conclusion:IL-10 (-819 C/T, -592 C/A) and IFNγ (+874 A/T) polymorphism might be related to RA in Japanese population. In addition, TGFβ1(+869 A/T) polymorphism might be associated with the production of anti-CCP antibody. These results suggest that the analyzing cytokine gene polymorphisms may offer promise as useful factors in the choice of treatment for Japanese RA patients.References:[1] Scott DL, Wolfe F, Huizinga TW. Rheumatoid arthritis. Lancet. 2010; 376: 1094–108.[2] McInnes IB, Schett G. Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol. 2007 Jun;7(6):429-42.Disclosure of Interests:None declared

The Molecular basis of Lactose Intolerance

2005 ◽  
Vol 88 (3) ◽  
pp. 157-202 ◽  
Author(s):  
Anthony K. Campbell ◽  
Jonathan P. Waud ◽  
Stephanie B. Matthews
Keyword(s):  
Rheumatoid Arthritis ◽  
Multiple Sclerosis ◽  
Molecular Basis ◽  
Charles Darwin ◽  
Lactose Intolerance ◽  
Anaerobic Bacteria ◽  
Bacterial Toxins ◽  
Systemic Symptoms ◽  
Lactase Gene ◽  
Over 40 Years

A staggering 4000 million people cannot digest lactose, the sugar in milk, properly. All mammals, apart from white Northern Europeans and few tribes in Africa and Asia, lose most of their lactase, the enzyme that cleaves lactose into galactose and glucose, after weaning. Lactose intolerance causes gut and a range of systemic symptoms, though the threshold to lactose varies considerably between ethnic groups and individuals within a group. The molecular basis of inherited hypolactasia has yet to be identified, though two polymorphisms in the introns of a helicase upstream from the lactase gene correlate closely with hypolactasia, and thus lactose intolerance. The symptoms of lactose intolerance are caused by gases and toxins produced by anaerobic bacteria in the large intestine. Bacterial toxins may play a key role in several other diseases, such as diabetes, rheumatoid arthritis, multiple sclerosis and some cancers. The problem of lactose intolerance has been exacerbated because of the addition of products containing lactose to various foods and drinks without being on the label. Lactose intolerance fits exactly the illness that Charles Darwin suffered from for over 40 years, and yet was never diagnosed. Darwin missed something else – the key to our own evolution – the Rubicon some 300 million years ago that produced lactose and lactase in sufficient amounts to be susceptible to natural selection.

GIANT BAKER'S CYST AND PSEUDOTHROMBOPHLEBITIS IN PATIENTS WITH RHEUMATIC DISEASES: A NEW INSIGHT INTO OLD COMPLICATIONS

2013 ◽  
Vol 16 (02) ◽  
pp. 1350009
Author(s):  
Massoud Saghafi ◽  
Azita Azarian
Keyword(s):  
Rheumatoid Arthritis ◽  
Rheumatic Diseases ◽  
Imaging Techniques ◽  
Cyst Formation ◽  
Underlying Disease ◽  
Popliteal Cyst ◽  
Baker’S Cyst ◽  
Baker's Cyst ◽  
Study Results ◽  
Prevalent Disease

Background: The knee joint is the most common site for cyst formation. Popliteal cyst may become large and its compressive effects produce complications particularly in subacute and chronic rheumatic diseases. Methods: We evaluated predisposing factors, underlying diseases, complications, course and management of giant Baker's cysts in our patients with rheumatic diseases. Patients with popliteal cysts that extended down lower than inferior level of the popliteal fossa, confirmed by imaging techniques were included in this retrospective study. Results: A total of 40 patients had giant Baker's cysts during last 20 years. Rheumatoid arthritis was the most prevalent disease in 21 patients (52.5%). Our cases included a large series of patients with seronegative spondyloarthropathies complicated with giant Baker's cyst in 10 patients (25%). Localized bulging, pain and tenderness of the calf region were observed in 15 patients (37.5%). A total of 25 patients had symptoms and signs similar to thrombophlebitis (62.5%). Rupture of Baker's cyst was detected in 10 patients (25%). A patient had giant Baker's cyst concurrent with thrombophlebitis. Management was mostly conservative including rest and intra-articular depoglucocorticoid injection with satisfactory results. Conclusions: In this study, rheumatoid arthritis was the most prevalent underlying disease and the pseudothrombophlebitis syndrome was the most prevalent presenting feature of patients with giant Baker's cysts.

Sign in / Sign up

Export Citation Format

Share Document