Adverse Events Profile of Low-dose Methotrexate in Nepalese Patients with Rheumatoid Arthritis: an Observational Study

Background: Methotrexate is considered as the anchor drug for the treatment of rheumatoid arthritis. However, various adverse effects limit its use leading to frequent discontinuation of treatment. This study aimed to evaluate the common adverse effects of methotrexate in patients with rheumatoid arthritis. Methods: A prospective observational study was conducted at National Center for Rheumatic Diseases from June 2018 to May 2019 among patients with rheumatoid arthritis using methotrexate monotherapy. Laboratory tests like liver function tests, renal function tests, complete blood count, C-reactive protein, erythrocyte sedimentation rate were done at baseline and every 3 months. Data on patients’ comorbidities, disease activity and side effects of drug were collected on every follow- up. Statistical analysis was carried out with the help of SPSS 23.0. Results: Out of 232 patients experiencing at least one adverse effect while on methotrexate monotherapy, 87.5% were female and mean age was 46.9±10.8 years. The mean dose of methotrexate was 16.6 ± 3.9 mg/week with the most frequently used dose of 20mg/week. Among the variety of adverse reaction observed, the most common was transaminitis (75.0%) with approximately 50.0% as isolated liver function abnormality, followed by nausea (19.4%), anorexia (12.9%), leukopenia (12.5%), oral ulcer (8.2%) and psychological intolerance (4.7%). Multiple regression analysis showed significant predictive value of body mass index for transaminitis (p-value 0.007). Conclusions: Asymptomatic liver function test derangement was the most frequent adverse-effect of methotrexate observed, whereas nausea and anorexia were the most common patient reported events. The frequent dose associated with side-effects in Nepalese patients was around 20mg/week. Keywords: Adverse events; methotrexate; Nepal; rheumatoid arthritis

Download Full-text

The German ACROSTUDY: past and present

Acta Endocrinologica ◽

10.1530/eje-09-0350 ◽

2009 ◽

Vol 161 (suppl_1) ◽

pp. S3-S10 ◽

Cited By ~ 52

Author(s):

M Buchfelder ◽

S Schlaffer ◽

M Droste ◽

K Mann ◽

B Saller ◽

...

Keyword(s):

Liver Function ◽

Adverse Events ◽

Observational Study ◽

Tumor Size ◽

Safety Data ◽

Rare Event ◽

Liver Function Tests ◽

Long Term Results ◽

Function Tests

Pivotal studies have demonstrated that pharmacotherapy with pegvisomant (Somavert) is a highly effective treatment for acromegaly. Since clinical experience with the drug was very limited, the Pegvisomant Observational Study was launched in Germany immediately with the drug becoming commercially available to patients early in 2004. Its purpose was to record safety and efficacy data on as many patients as possible. As of 12th August 2008 a total of 371 patients (185 males, 186 females) had been included in the study. They were on pegvisomant therapy for an average of 118 weeks. Median and mean doses of pegvisomant were 15 and 16.4 mg/day respectively. Treatment efficacy was monitored by IGF1 levels and the patients symptoms were evaluated by completion of a questionnaire (patient-assessed acromegaly symptom questionnaire). Safety data included liver function tests, fasting glucose, HbA1c measurements, and tumor size monitoring by repeated magnetic resonance imaging. Normalization of IGF1 ranged from 55.7% of the 273 patients assessed after 6 months to 71.3% of 202 patients assessed after 24 months of treatment. It was 70.7% after 36 months (133 patients), 64.8% at 48 months (71 patients), and 58.4% after 60 months (24 patients). In 39 patients (10.9%) treatment was discontinued due to serious adverse events or adverse events with 25 (6.7%) of these patients having a potential causal relationship with the pegvisomant treatment. Liver function tests became abnormal in 20 patients and another three patients were recorded to have hepatobiliary disorders. Tumor size increase was reported in 20 patients, but only confirmed in nine patients by careful revision of all available images. Local injection site reactions were observed in 12 patients. In conclusion, in this large group of pegvisomant-treated patients, long-term data for up to 5 years of treatment are now available. In 71.3% of patients with previously not sufficiently treatable acromegaly, IGF1 levels were normalized by pegvisomant therapy. Elevated transaminases usually normalized after discontinuation but in half of the affected patients also despite continuation of treatment without dose alteration. Tumor progression was a rare event. It did not exceed the expected rate in patients with acromegaly not treated with pegvisomant. As from this presently largest database of acromegalic patients treated with pegvisomant, long-term results are encouraging. The German data are now merged into the global ACROSTUDY and will constitute a major portion of the international ACROSTUDY project as a continuing global web-based observational study.

Download Full-text

Association between Inflammatory Cytokines and Liver Functions in Rheumatoid Arthritis Patients

Sudan Journal of Medical Sciences ◽

10.18502/sjms.v16i2.9294 ◽

2021 ◽

Author(s):

Mohamed Abdelrhman Eltahir ◽

Kawthar Abdelgaleil Mohammedsalih ◽

Elhaj Noureldien Mohamed ◽

Faisal Makki Babekir ◽

Amar Mohamed Ismail

Keyword(s):

Rheumatoid Arthritis ◽

Young Adults ◽

Liver Function ◽

Inflammatory Cytokines ◽

Liver Function Tests ◽

P Value ◽

Interleukin 17 ◽

Function Tests ◽

Liver Functions ◽

Anti Inflammatory

Background: Rheumatoid arthritis (RA) is associated with abnormal liver tests, and the medications used for RA are often hepatotoxic. Therefore, this study aimed to investigate an association between pro-inflammatory and anti-inflammatory cytokines and liver function tests in RA patients. Methods: In this descriptive cross-sectional study, 88 RA patients were included, 84 of them were women and 4 men, aged 21–81 years. Serum interleukin-10 (IL-10), interleukin-17 (IL-17), Osteopontin (OPN) were measured and liver function tests were conducted. Results: The frequency of RA was higher among adults aged >41 years (72 [81.8%]) than young adults aged ≤41 years (16 [18.2%]). RA was more common in women (84 [95.5%]) than in men (4 [4.5%]) – approximately 21:1-fold. Young adults had higher abnormal IL-10 than adult RA patients (OR = 3.72, p-value 0.044). Abnormal IL-17 (OR = 5.67, p-value 0.034) was found to be increased in young-adult RA patients. No association was observed between age and OPN and between the duration of disease and IL-10, IL-17, and OPN. Similarly, no association was noted between the types of treatment and IL-10, IL-17, and OPN, nor between IL-10, IL-17, OPN and liver parameters (AST, ALT, ALP, ALB, TP, and GGT). Conclusion: Pro-inflammatory and anti-inflammatory cytokines are not associated with abnormal liver functions, as has been demonstrated in RA patients.

Download Full-text

Continuous effectiveness and safety after a hospital-wide switch to adalimumab biosimilar: an observational study in rheumatoid arthritis patients

10.21203/rs.3.rs-315232/v1 ◽

2021 ◽

Author(s):

Rianne Brouwer ◽

Peter M. ten Klooster ◽

Joost B. Masselink ◽

Harald E. Vonkeman

Keyword(s):

Rheumatoid Arthritis ◽

Side Effects ◽

Observational Study ◽

Disease Activity ◽

Functional Disability ◽

Activity Levels ◽

Cross Sectional Survey ◽

Cross Sectional ◽

Sf 36 ◽

Patient Reported

Abstract Objectives Only few observational studies have investigated the actual effectiveness of switching to biosimilars in daily clinical practice in unselected patients. The objective of this study was to examine the maintenance of effect and safety after a hospital-wide switch for economic reasons from adalimumab originator Humira® to biosimilar Amgevita® in real-world rheumatoid arthritis (RA) patients and patient satisfaction with the switch. Methods A single centre retrospective observational study of RA patients on the course of their disease activity (DAS28, ESR and CRP), health-related quality of life (SF-36) and functional disability (HAQ-DI) before and up to one year after the switch, supplemented with a cross-sectional survey on satisfaction and experienced side effects approximately 18 months after the switch. Treatment outcomes were analysed with linear mixed modelling and generalized estimation equations. Results On November 1st 2018, 239 rheumatology patients switched to the adalimumab biosimilar. Of 52 RA patients who met the inclusion criteria sufficient data were available. Disease activity levels, the proportion of patients in remission (DAS28 < 2.6), and SF-36 and HAQ-DI scores did not significantly change from before the switch. 38 of the 52 analysed patients returned the questionnaire. Overall, patients were satisfied with the switch. Three patients (7.9%) stopped the biosimilar due to side effects. Conclusion Switching to the adalimumab biosimilar did not result in increased disease activity or worse patient-reported outcomes over an observation period of 9 to 12 months. Also, there was no apparent evidence of increased side effects. Patients themselves were mostly satisfied with the switching experience.

Download Full-text

Adverse events with ayurvedic medicines- possible adulteration and some inherent toxicities

Wellcome Open Research ◽

10.12688/wellcomeopenres.15096.2 ◽

2019 ◽

Vol 4 ◽

pp. 23

Author(s):

Buddhi Paudyal ◽

Astha Thapa ◽

Keshav Raj Sigdel ◽

Sudeep Adhikari ◽

Buddha Basnyat

Keyword(s):

Rheumatoid Arthritis ◽

Nephrotic Syndrome ◽

Side Effects ◽

Adverse Effects ◽

Adverse Events ◽

Indian Subcontinent ◽

Ayurvedic Medicine ◽

Gold Salt ◽

Traditional System ◽

Wide Range

Ayurvedic medicine, a traditional system of medicine practiced in the Indian subcontinent is considered to be devoid of adverse effects. We report three cases which highlight the possibility of adverse events related with the use ofwith the use of ayurvedic products. A 35 years old woman with hepatitis took ayurvedic powder medicine and with swarnabhasma (gold salt)s and had her liver injury worsened, possibly due to alkaloids, and developed nephrotic syndrome, possibly due to and gold salt. A 57 years old hypertensive man was taking ayurvedic medicine containing reserpine which had long been withdrawn from the allopathic system of medicine due to wide range of side effects. A 47 years old woman with rheumatoid arthritis was taking an unknown tablet containing a steroid as an adulterant for 2 years and developed side effects typical of steroid excess. We like to highlight the fact that ayurvedic medicines do have propensity to may cause adverse effects due to adulterations or inherent constituents like alkaloids, and hence are may not always be completely safe.

Download Full-text

The Use of Methotrexate in Rheumatoid Arthritis

Drug Intelligence & Clinical Pharmacy ◽

10.1177/106002808501900503 ◽

1985 ◽

Vol 19 (5) ◽

pp. 349-358 ◽

Cited By ~ 8

Author(s):

Peter W. Letendre ◽

Douglas J. DeJong ◽

Donald R. Miller

Keyword(s):

Rheumatoid Arthritis ◽

Clinical Trials ◽

Folic Acid ◽

Side Effects ◽

Adverse Effects ◽

Systemic Administration ◽

Refractory Disease ◽

Controlled Clinical Trials ◽

Folic Acid Antagonist ◽

Acid Antagonist

The use of methotrexate in rheumatoid arthritis is reviewed. Methotrexate, a folic acid antagonist, is sometimes employed in an attempt to symptomatically control patients whose disease does not respond adequately to conventional therapies. Systemic administration of 7.5–15 mg/wk in a “pulse” fashion appears to be effective without precipitating severe adverse effects. However, concern over potentially serious side effects and a lack of well-controlled clinical trials have limited its use to severe, refractory disease. Further studies are needed before its role in rheumatoid arthritis can justifiably be expanded.

Download Full-text

POS0441 DEVELOPMENT OF RHEUMATOID ARTHRITIS AMONG ANTI-CITRULLINATED PROTEIN ANTIBODIES POSITIVE ASYMPTOMATIC INDIVIDUALS: A PROSPECTIVE OBSERVATIONAL STUDY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.344 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 449.1-449

Author(s):

S. Mizuki ◽

K. Horie ◽

K. Imabayashi ◽

K. Mishima ◽

K. Oryoji

Keyword(s):

Rheumatoid Arthritis ◽

Risk Factors ◽

Observational Study ◽

Rheumatoid Factor ◽

Prospective Observational Study ◽

Enzyme Linked Immunosorbent Assay ◽

P Value ◽

Healthy Population ◽

Asymptomatic Individuals ◽

Citrullinated Protein

Background:In the idividuals with genetic and enviromental risk factors, immune events at mucosal surfaces occur and may precede systemic autoimmunity. Anti-citrullinated protein antibodies (ACPA) are present in the serum for an average of 3-5 years prior to the onset of rheumatoid arthritis (RA) during an asymptomatic period. In ACPA-positivite individuals, the additional presence of RA-related risk factors appears to add significant power for the development of RA. To date, there have been few reports in which clinical courses of ACPA-positive asymptomatic individuals were investigated prospectively.Objectives:To observe the clinical time course of ACPA-positive healthy population for the development of RA.Methods:Healthy volunteers without joint pain or stiffness, who attended the comprehensive health screening of our hospital, were enrolled in this prospective observational study. The serum ACPA levels were quantified by Ig-G anti-cyclic citrullinated peptide enzyme-linked immunosorbent assay with levels > 4.4 U/mL considered positive. ACPA-positive subjects were followed by rheumatologists of our department clinically or a questionnaire sent by mail for screening to detect arthritis.Results:5,971 healthy individuals without joint symptons were included. Ninty-two (1.5%) were positive for ACPA. Of these, 19 (20.7%) developed RA and two were suspected as RA by mail questionnaire. Their average age were 58-years, and women were 68%. The average duration between the date of serum sampling and diagnosis was 10.7 months. ACPA-positive individuals who developed to RA had higher serum ACPA and Ig-M rheumatoid factor levels than ACPA-positive individuals who did not (P value by Mann-Whitney U test: 0.002, 0.005, respectively).Conclusion:Among ACPA-positive asymptomatic individuals, 20% developed RA. The higher titer of ACPA and Ig-M rheumatoid factor levels are risk factors for devoloping RA.Disclosure of Interests:None declared

Download Full-text

P037 DMARDs & hepatitis E: the hidden culprit

Rheumatology ◽

10.1093/rheumatology/keab247.034 ◽

2021 ◽

Vol 60 (Supplement_1) ◽

Author(s):

Geraint A Brown ◽

Louise Kearney ◽

Elizabeth Warner ◽

Spencer Ellis

Keyword(s):

Rheumatoid Arthritis ◽

Liver Function ◽

Liver Function Tests ◽

Hepatitis E ◽

British Society ◽

Good Effect ◽

Solid Organ ◽

Seropositive Rheumatoid Arthritis ◽

Function Tests ◽

Contaminated Food

Abstract Background/Aims Disease-modifying anti-rheumatic drugs (DMARDs) require blood monitoring as recommended by the British Society for Rheumatology guidelines. Deranged liver function tests are a common abnormality, and when a significant transaminitis occurs further investigations are required. We wish to present three cases where a transaminitis was caused by acute hepatitis E. Hepatitis E rarely causes illness in the general population. Transmission can occur via sewage-contaminated food and water, undercooked or raw pig and game meat, or processed pork and shellfish. Blood transfusion and solid organ transplantation is very rare. There is an estimated 60,000 cases of Hepatitis E per year in England. Those who are immunosuppressed are more likely to develop chronic liver disease. Methods . Results Case 1 is 55 year old male with a seronegative inflammatory arthritis treated with methotrexate and sulfasalazine whose ALT rose to 2043 U/l. After a negative liver screen including autoantibodies, Hepatitis E IgM was detected. Case 2 is a 71 year old male with seropositive rheumatoid arthritis prescribed Methotrexate and Sulfasalazine who developed a transaminitis following a holiday to Spain. Hepatitis E serology was positive. Case 3 is a 65 year old male with seropositive rheumatoid arthritis on Abatacept and Methotrexate who also developed deranged liver function tests following a trip to Spain. Alcohol excess was initially suspected due to the consumption of > 20 units per week. However, on cessation of all medications the ALT continued to rise to 1087 U/l. He was found to be Hepatitis E IgM positive with viral PCR also detected. In all three cases contaminated food was likely to be the source of infection and DMARDs were successfully restarted in all patients following normalisation of liver function tests. Conclusion This case series highlights an important differential for transaminitis with very little published literature. Hepatitis E is under reported and not routinely requested in practice as part of a liver screen. Failure to check Hepatitis E serology may lead to DMARDs being discontinued inappropriately. All patients should be educated about the risks of Hepatitis E from food products.We recommend that DMARDs are suspended once Hepatitis E infection has been diagnosed in order to allow the immune system combat the infection. Treatment is usually self limiting, though in severe cases Ribavirin has been used with good effect. DMARDs should be restarted once liver markers normalise, and two serum Hepatitis E RNA results and two stool samples are negative. The presence of persistent Hepatitis E RNA (viral shedding) is highly suspicious for chronic infection, which would warrant hepatology input. Disclosure G.A. Brown: None. L. Kearney: None. E. Warner: None. S. Ellis: None.

Download Full-text

POS0642 THE IMPACT OF AGE ON DISCONTINUATION OF BIOLOGIC DMARDs IN PATIENTS WITH RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3759 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 559.2-560

Author(s):

V. Rivera Teran ◽

S. Sicsik ◽

D. Vega-Morales ◽

F. Irazoque-Palazuelos ◽

D. Miranda ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Adverse Effects ◽

Adverse Events ◽

Cox Regression ◽

Retention Rate ◽

Drug Discontinuation ◽

Discontinuation Rate ◽

Biologic Dmards ◽

Conventional Dmards ◽

The Impact

Background:Rheumatoid arthritis (RA) is the most common autoimmune disease. Older patients treated with biologic DMARDs (bDMARDs) are at a significantly greater risk of adverse effects (AEs) [1]. However, the rate of drug discontinuation because of adverse effects caused by bDMARDs has not differed in elderly compared to younger patients in different registries.Objectives:Determine if drug discontinuation of bDMARDs differs by age in patients with rheumatoid arthritis in the Mexican Adverse Events Registry (BIOBADAMEX).Methods:BIOBADAMEX is a Mexican ongoing cohort of patients using bDMARDs since 2016. In this analysis we included all patients with diagnosis of RA with at least two assessments. Survival on bDMARDs was estimated using Kaplan-Meier analysis. Predictors of discontinuation, including age older than median age in the sample were investigated by Cox regression analyses.Results:Among 743 patients in the registry, 497 had RA diagnosis, from which, 214 had at least two assessments. At baseline, patients had a median (IQR) age of 53.4 (45-61) years old, median disease duration of 10.7 (6-17) months and median DAS28 of 4.7 (3-6). Conventional DMARDS were used by 185 (87%) patients and 94 (44%) patients used corticosteroids. Comorbidities were present in 194 (91%). The most common bDMARDs received at baseline were abatacept 59 (27%), tocilizumab 45(21%), adalimumab 31 (15%) and certolizumab 30 (14%). At the time of analysis, the median bDMARDs treatment duration was 21.0(13-34) months, 128 (59%) had discontinued treatment, 66 for inefficacy, 32 for adverse events and 30 for others. Fig 1 shows discontinuation rate curves in patients younger and older than median age. Cox proportional-hazards demonstrated no significant differences regarding age older than median age (HR 1.1, 95% CI 0.8-1.4, p=0.7), female sex (HR 1.2, 95% CI 0.7-1.9, p=0.44), use of corticosteroids (HR 1.2, 95% CI 0.9-1.6, p=0.20), comorbidities (HR 0.9, 95% 0.6-1.5, p=0.78), DAS28 (HR 0.9, 95% 0.9-1.1, p=0.93) or other factors.Figure 1.Discontinuation rate curves in patients younger and older than median age (< 53.4 and >=53.4 years old)Conclusion:This analysis did not show a role of age on discontinuation of bDMARDs in Mexican RA patients. Further longitudinal analyses will be performed including more patients to assess retention rate of bDMARDs and identify predictive variables of discontinuation in Mexican population.References:[1]Akter R, et al. Can Geriatr J. 2020 May 1;23(2):184-189.[2]Ikari Y, et al. Medicine (Baltimore). 2020 Dec 24;99(52):e23861.Disclosure of Interests:None declared

Download Full-text

Determinants Associated with Work Participation in Patients with Established Rheumatoid Arthritis Taking Tumor Necrosis Factor Inhibitors

The Journal of Rheumatology ◽

10.3899/jrheum.130878 ◽

2014 ◽

Vol 41 (7) ◽

pp. 1263-1269 ◽

Cited By ~ 4

Author(s):

Sofie H.M. Manders ◽

Wietske Kievit ◽

Annemarie L.M.A. Braakman-Jansen ◽

Herman L.M. Brus ◽

Lidy Hendriks ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Tumor Necrosis Factor ◽

Disease Activity ◽

Functional Status ◽

Tumor Necrosis ◽

Work Participation ◽

P Value ◽

Retirement Pension ◽

Patient Reported ◽

Necrosis Factor

Objective.Reduced work participation (WP) is a common problem for patients with rheumatoid arthritis (RA) and generates high costs for society. Therefore, it is important to explore determinants of WP at the start of tumor necrosis factor inhibitor (TNFi) treatment, and for changes in WP after 2 years of TNFi treatment.Methods.Within the Dutch Rheumatoid Arthritis Monitoring (DREAM) biologic register, WP data were available from 508 patients with RA younger than 65 years and without an (early) retirement pension. WP was registered at start of TNFi treatment and after 2 years of followup and was measured by single patient-reported binary questions whether they had work, paid or voluntary, or had a disability allowance or a retirement pension. Determinants measured at baseline were age, sex, disease duration, functional status [through Health Assessment Questionnaire-Disability Index (HAQ-DI)], 28-joint Disease Activity Score (DAS28), rheumatoid factor, presence of erosions, number of previous disease-modifying antirheumatic drugs, and number of comorbidities. During the 2 years of followup, HAQ-DI response and European League Against Rheumatism response were measured. Univariate analyses (excluded if p value was > 0.2) and multivariate (excluded if p value was > 0.1) logistic regression analyses were used.Results.Determinants associated with WP at baseline were having a better HAQ-DI (OR 0.32, p = 0.000) and male sex (OR 0.65, p = 0.065). After 2 years of TNFi therapy, 11.8% (n = 60) started to work and 13.6% (n = 69) stopped working. Determinants associated with starting to work were better baseline HAQ-DI (OR 0.58), positive RF (OR 2.73), and young age (OR 0.96); and for stopping work, worse baseline HAQ-DI (OR 2.74), low HAQ-DI response (OR 0.31), and comorbidity (OR 2.67), all with p < 0.1.Conclusion.Young patients with RA and a high functional status without any comorbidity will have a better chance of working. This supports the main goal in the management of RA: to suppress disease activity as soon and as completely as possible to prevent irreversible destruction of the joints, and thus maintain a good functional status of the patient. Because of the low proportion of variance explained by the models in this study, other factors besides the ones studied are associated with WP.

Download Full-text