scholarly journals SAT0137 METHOTREXATE ASSOCIATED ADVERSE EVENTS AND THEIR PREDICTORS IN METHOTREXATE-NAÏVE PATIENTS WITH RHEUMATOID ARTHRITIS: A SYSTEMATIC REVIEW

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1005.2-1006
Author(s):  
A. Sherbini ◽  
S. Sharma ◽  
J. Gwinnutt ◽  
K. Hyrich ◽  
S. Verstappen
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Events ◽  
Observational Studies ◽  
Liver Enzymes ◽  
Forest Plot ◽  
Research Support ◽  
High Baseline ◽  
Pooled Prevalence ◽  
Elevated Liver Enzymes ◽  
Increased Risk

Background:The adverse events (AEs) associated with methotrexate (MTX) treatment for rheumatoid arthritis (RA) have been studied extensively, but precise estimates of the incidence and prevalence of AEs are lacking. There is also limited published data on the predictors of AEs.Objectives:To summarise and pool incidence and prevalence rates of AEs in patients treated with MTX for RA, and to identify treatment, clinical and disease related predictors of AEs.Methods:A systematic literature search was carried out using Embase, Medline, and CENTRAL databases to identify relevant studies published between 1/1/2005 and 12/2/2019. The eligibility criteria included RCTs, non-randomized trials, and observational studies of first-time users of MTX in adults (≥ 18 years old) with RA and reported incidence, prevalence or predictors of the most common MTX related AEs, including: any AE, serious AEs, discontinuation due to AEs, elevated liver enzymes, gastrointestinal (GI), mucocutaneous (MC), central nervous system (CNS), and pulmonary AEs. Pooled proportions of GI AEs and elevated liver enzymes of patients treated with MTX monotherapy were estimated using random effects meta-analysis.Results:Of 3142 records screened, we included 46 articles (35 clinical trials and 11 cohort studies) with a total of 9646 patients, and a mean follow-up duration of 70±35 weeks (range: 13 - 104 weeks for RCTs, 40 - 156 weeks for observational cohorts).Six studies reported incidence rate (IR) of any AE (range: 196 - 595 per 100 person-years), and eight studies reported IR of serious AEs (range: 3.7 - 15.9 per 100 person-years). The percentage of patients with any AE, reported in 32 studies, varied between 37% and 100% in RCTs, and between 13% and 34% in observational studies. Discontinuation of MTX due to AEs ranged between 1% and 29% in RCTs, and between 8% and 38% in observational studies. The reported prevalence of MC events (4% - 54%), CNS events (12% - 59%) and pulmonary events (10% - 67%) varied between studies.The estimated pooled prevalence from studies with a MTX monotherapy arm was 14% (95% CI: 9%, 19%; N=7 studies) for liver enzymes elevation (Figure 1), and 29% (95% CI: 13%, 44%; N=7 studies) for GI AEs (Figure 2).Figure 1.Forest plot of pooled prevalence of elevated liver enzymesFigure 2.Forest plot of pooled prevalence of gastrointestinal adverse eventsNo statistically significant predictors of “any AE” were identified. For discontinuation of MTX due to AEs, RF positivity was associated with lower risk of MTX discontinuation due to MTX (HR 0.37, 95%CI: 0.21, 0.64), while other studies found that baseline HAQ score (OR 1.87, 95%CI: 1.11, 3.15) and BMI (OR 1.21, 95%CI: 1.02, 1.44) were associated with increased risk of MTX discontinuation due to AEs. ACPA positivity (OR 1.8, 95%CI: 1.1, 3.1), and high baseline alanine aminotransferase (ALT) (OR 3.1, 95%CI: 1.6, 6.2) were both independent predictors of two-fold elevation of ALT in one paper, and baseline creatinine (OR 1.03, 95%CI: 1.00, 1.07) and high baseline ALT (OR 1.03, 95%CI: 1.00, 1.06) were associated with increased risk of elevated ALT above the upper limit of normal in a different study.Conclusion:These findings affirm the high prevalence of GI AEs and elevated liver enzymes among patients treated with MTX for RA. The identified predictors of MTX withdrawal and elevated ALTs may be useful for identifying future patients likely to experience these AEs early in the course of treatment. However, the results of the predictors should be interpreted with caution, and further work is needed to replicate the results in studies with larger sample sizes and to assess the prognostic value of established predictors.Disclosure of Interests:Ahmad Sherbini: None declared, Seema Sharma: None declared, James Gwinnutt Grant/research support from: BMS, Kimme Hyrich Grant/research support from: Pfizer, UCB, BMS, Speakers bureau: Abbvie, Suzanne Verstappen Grant/research support from: BMS, Consultant of: Celltrion, Speakers bureau: Pfizer

scholarly journals O06 Baseline predictors of methotrexate-related adverse events in methotrexate-naïve patients with RA

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Ahmad A Sherbini ◽  
James M Gwinnutt ◽  
Kimme L Hyrich ◽  
Suzanne M M Verstappen ◽  
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Events ◽  
Health Assessment ◽  
Prevalence Rates ◽  
Clinical Predictors ◽  
Research Support ◽  
Related Data ◽  
Increased Risk ◽  
One Year

Abstract Background/Aims  Methotrexate (MTX) is the most common treatment for rheumatoid arthritis (RA). The prevalence of adverse events (AEs) associated with MTX treatment for RA have been studied extensively, but there are limited data on the predictors of these AEs. This study aims to summarise the prevalence rates of MTX AEs, including gastrointestinal (GI), neurological, mucocutaneous, and elevated alanine transaminase (ALT) enzyme, and to identify baseline demographic and clinical predictors of these AEs. Methods  The Rheumatoid Arthritis Medication Study (RAMS) is a UK multi-centre prospective cohort study of patients with RA starting MTX for the first time. Relevant demographic, medication, clinical and disease related data were collected at baseline. AEs were reported at six and twelve months follow-ups. The prevalence rates of AEs were calculated based on the proportions of patients who reported having had an AE within one year of follow-up. The associations between candidate baseline predictors and AEs were assessed using multivariable logistic regression. Results  A total of 2,089 patients were included with a mean age of 58.4 (standard deviation: 13.5) years, 1390 (66.5%) were women. 1,814 and 1,579 patients completed the 6 and 12 months follow-up visits, respectively. The prevalence rates of the AEs within one year of follow-up were: GI = 777 (40.6%), mucocutaneous = 441 (23.1%), neurological = 487 (25.5%), elevated ALT (> upper limit of normal [ULN]) = 286 (15.5%). Younger age and being a woman were associated with increased risk of GI AEs, (age: OR 0.97 per year increase in age, 95% CI 0.98, 1.00; male sex: OR 0.58 vs female, 95% CI 0.46, 0.74) (Table 1). Higher baseline Health Assessment Questionnaire (HAQ) score was an independent predictor of GI, mucocutaneous, and neurological AEs. Furthermore, having ALT >1xULN at baseline or history of diabetes was associated with increased risk of subsequent ALT elevation during the study follow-up. Conclusion  In patients with RA starting MTX, GI AEs were the most commonly reported AEs during the first year of follow-up. The identified predictors of AEs may facilitate discussions between clinicians and patients prior to commencing MTX, and may lead to increased adherence and consequently improved effectiveness. Disclosure  A.A. Sherbini: None. J.M. Gwinnutt: Grants/research support; BMS. K.L. Hyrich: Member of speakers’ bureau; Abbvie. Grants/research support; Pfizer, UCB, BMS. S.M.M. Verstappen: Consultancies; Celltrion. Member of speakers’ bureau; Pfizer. Grants/research support; BMS.

scholarly journals OP0098 POLYPHARMACY IS ASSOCIATED WITH A POORER TREATMENT RESPONSE AND INCREASED RISK OF ADVERSE EVENTS IN EARLY RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 54.1-54
Author(s):  
S. Benamar ◽  
C. Lukas ◽  
C. Daien ◽  
C. Gaujoux-Viala ◽  
L. Gossec ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Events ◽  
Treatment Response ◽  
Univariate Analysis ◽  
Group Versus ◽  
Biological Database ◽  
Lower Probability ◽  
Research Support ◽  
Early Ra ◽  
Increased Risk

Background:Polypharmacy is steadily increasing in patients with rheumatoid arthritis (RA). They may interfere with treatment response and the occurrence of serious adverse events. Medications taken by a patient may reflect active comorbidities, whereas comorbidity indices usually used include past or current diseases.Objectives:To evaluate whether polypharmarcy is associated with treatment response and adverse events in an early RA cohort and to establish whether polypharmacy could represent a substitute of comorbidities.Methods:We used data from the French cohort ESPOIR, including 813 patients with early onset arthritis. Patients included the current study had to start their first disease modifying anti-rheumatic drug (DMARD) within 24 months of inclusion in the cohort. Disease activity data were collected at one, five and ten years from the initiation of the first DMARD. For each patient, treatments were collected at baseline and at five years. Medications count included all specialties other than background RA therapy, analgesics/NSAIDs and topicals. Polypharmacy was defined as a categorical variable based on the median and tertiles of distribution in the cohort. Treatment response was assessed by achieving DAS28 ESR remission (REM) at 1 year, 5 years and 10 years from the initiation of the first DMARD. The occurrence of severe adverse events (SAE) was measured by the occurrence of severe infection, hospitalization, or death during the 10-year follow-up. The association between patient’s characteristics and achievement of REM and occurrence of SAE were tested in univariate analysis. A logistic regression model was used to evaluate associations between polypharmacy and REM at 1 year, 5 years and 10 years (we used baseline polypharmacy for the 1-year analysis and five years polypharmacy for the 5- and 10-years analyses). Multivariate adjustment was made for age, sex, BMI, duration of disease, initial DAS28 ESR, initial HAQ, smoking status, rheumatic disease comorbidity index (RDCI).Results:The proportion of patients who achieved REM one year after the initiation of the first DMARD was 32.1% in the polypharmacy according to the median group (patients taken ≥2 medication) versus 67.9% in the non-polypharmacy group (p=0.07). At 5 years after the first DMARD, the proportion of patients with REM was 45.0% in the polypharmacy group versus 56.3% in the non-polypharmacy group (p=0.03). At 10 years the proportion of patients with REM was 32.5% in the polypharmacy group versus 67.5% (p=0.06). Patients who take greater or equal to 2 medications had a 40% lower probability of achieving REM (OR = 0.60 [0.38-0.94] p = 0.03) at 5 years from the first DMARD (if RDCI index was not included in the model). At 10 years, patients receiving multiple medications had a 43% lower probability of achieving REM (OR = 0.57 [0.34-0.94] p = 0.02). SAE incidence was 61 per 1000 patient-years. For patients who developed SAE all causes 71.4% where in the polypharmacy group versus 57.8% were in the non-polypharmacy group (p = 0.03; univariate analysis). These results are no longer significant after adjustment for comorbidities indices.Conclusion:In this early RA cohort, polypharmacy is associated with a poorer treatment response and increased risk of adverse events. Polypharmacy may represent a good substitute of comorbidities for epidemiological studies.Acknowledgements:We are grateful to Nathalie Rincheval (Montpellier) who did expert monitoring and data management and all theinvestigators who recruited and followed the patients (F. Berenbaum, Paris-Saint Antoine; MC. Boissier, Paris-Bobigny; A. Cantagrel, Toulouse; B. Combe, Montpellier; M. Dougados, Paris-Cochin; P. Fardellone and P. Boumier, Amiens; B. Fautrel, Paris-La Pitié; RM. Flipo, Lille; Ph. Goupille, Tours; F. Liote, Paris- Lariboisière; O. Vittecoq, Rouen; X. Mariette, Paris-Bicêtre; P. Dieude, Paris Bichat; A. Saraux, Brest; T. Schaeverbeke, Bordeaux; and J. Sibilia, Strasbourg).The work reported on in the manuscript did not benefit from any financial support. The ESPOIR cohort is sponsored by the French Society for Rheumatology. An unrestricted grant from Merck Sharp and Dohme (MSD) was allocated for the first 5 years. Two additional grants from INSERM were obtained to support part of the biological database. Pfizer, Abbvie, Lilly and more recently Fresenius and Biogen also supported the ESPOIR cohort.Disclosure of Interests:Soraya Benamar: None declared, Cédric Lukas Speakers bureau: Abbvie, Amgen, Janssen, Lilly, MSD, Novartis, Pfizer, Roche-Chugai, UCB, Consultant of: Abbvie, Amgen, Janssen, Lilly, MSD, Novartis, Pfizer, Roche-Chugai, UCB, Grant/research support from: Pfizer, Novartis and Roche-Chugai, Claire Daien Speakers bureau: AbbVie, Abivax, BMS, MSD, Roche, Chugai, Novartis, Pfizer, Sandoz, Lilly, Consultant of: AbbVie, Abivax, BMS, MSD, Roche, Chugai, Novartis, Pfizer, Sandoz, Lilly, Cécile Gaujoux-Viala Speakers bureau: Abbvie, BMS, Celgene, Janssen, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi, Roche-Chugai, UCB, Consultant of: Abbvie, BMS, Celgene, Janssen, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi, Roche-Chugai, UCB, Grant/research support from: Pfizer, Laure Gossec Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis et UCB, Consultant of: AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis et UCB, Anne-Christine Rat Speakers bureau: Pfizer, Lilly, Consultant of: Pfizer, Lilly, Bernard Combe Speakers bureau: AbbVie; Bristol-Myers Squibb; Gilead; Janssen; Lilly; Merck; Novartis; Pfizer; Roche-Chugai; and Sanofi;, Consultant of: AbbVie; Bristol-Myers Squibb; Gilead; Janssen; Lilly; Merck; Novartis; Pfizer; Roche-Chugai; and Sanofi;, Grant/research support from: Novartis, Pfizer, and Roche-Chugai., Jacques Morel Speakers bureau: Abbvie, BMS, Lilly, Médac, MSD, Nordic Pharma, Pfizer, UCB, Consultant of: Abbvie, BMS, Lilly, Médac, MSD, Nordic Pharma, Pfizer, UCB, Grant/research support from: BMS, Pfizer

scholarly journals AB1335-HPR HEALTH PROFESSIONALS’ PERSPECTIVE ON THE BENEFITS AND RISKS OF LOW-DOSE GLUCOCORTICOIDS IN RHEUMATOID ARTHRITIS – AN INTERNATIONAL SURVEY OF 444 HEALTH PROFESSIONALS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1955.1-1956
Author(s):  
T. Santiago ◽  
M. Voshaar ◽  
M. De Wit ◽  
P. Carvalho ◽  
M. Boers ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Events ◽  
Health Professionals ◽  
Patient Perspective ◽  
Online Survey ◽  
Low Dose ◽  
Low Doses ◽  
Research Support ◽  
Serious Adverse Events ◽  
Patient Organizations

Background:The Glucocorticoid Low-dose Outcome in Rheumatoid Arthritis Study (GLORIA) is an international investigator-initiated pragmatic randomized trial designed to study the effects of low-dose glucocorticoids (GCs) in elderly patients with Rheumatoid Arthritis (RA).The research team is also committed to promote a better understanding of the risks and benefits of these drugs among health professionals and patients. In order to achieve these goals, it is important to assess the current ideas and concerns of patients regarding GCs.Objectives:To evaluate the current patient perspective on the efficacy and risks of GCs in RA patients who are or have been treated with GCs.Methods:Patients with RA completed an online survey (with 5 closed questions regarding efficacy and safety) presented in their native language. RA patients were recruited through a variety of patient organizations representing three continents. Patients were invited to participate through national patient organizations. In the USA, patients were also invited to participate through MediGuard.org. Participants were asked for their level of agreement on a 5-point Likert scale.Results:1344 RA patients with exposure to GCs, from Brazil, USA, UK, Portugal, Netherlands, Germany and 24 other countries** participated: 89% female, mean age (SD) 52 (14) years and mean disease duration 13 (11) years. The majority of participants (84%) had ≥10 years of education. The duration of GCs exposure was 1.6 (4.2) years. The majority of participants had read articles or pamphlets on the benefits or harms of GC therapy.Regarding GCs efficacy (table 1), high levels of endorsement were found: about 2/3 of patients considered that GCs as very useful in their case, more than half considered that GCs were effective even at low doses, and agreed that GC improved RA symptoms within days.Regarding safety (table 1), 1/3 of the participants reported having suffered some form of serious adverse events (AEs) due to GCs, and 9% perceived this as “life-threatening. Adverse events had a serious impact on quality of life, according to about 1/3 of the respondents.Conclusion:Patients with RA exposed to GC report a strong conviction that GCs are very useful and effective for the treatment of their RA, even at low doses. This is accompanied by an important prevalence of serious AEs. Understanding the patient perspective can improve shared decision-making between patient and rheumatologist.Funding statement:This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 634886.Disclosure of Interests:Tânia Santiago: None declared, Marieke Voshaar Grant/research support from: part of phd research, Speakers bureau: conducting a workshop (Pfizer), Maarten de Wit Grant/research support from: Dr. de Wit reports personal fees from Ely Lilly, 2019, personal fees from Celgene, 2019, personal fees from Pfizer, 2019, personal fees from Janssen-Cilag, 2017, outside the submitted work., Consultant of: Dr. de Wit reports personal fees from Ely Lilly, 2019, personal fees from Celgene, 2019, personal fees from Pfizer, 2019, personal fees from Janssen-Cilag, 2017, outside the submitted work., Speakers bureau: Dr. de Wit reports personal fees from Ely Lilly, 2019, personal fees from Celgene, 2019, personal fees from Pfizer, 2019, personal fees from Janssen-Cilag, 2017, outside the submitted work., Pedro Carvalho: None declared, Maarten Boers: None declared, Maurizio Cutolo Grant/research support from: Bristol-Myers Squibb, Actelion, Celgene, Consultant of: Bristol-Myers Squibb, Speakers bureau: Sigma-Alpha, Frank Buttgereit Grant/research support from: Amgen, BMS, Celgene, Generic Assays, GSK, Hexal, Horizon, Lilly, medac, Mundipharma, Novartis, Pfizer, Roche, and Sanofi., José Antonio P. da Silva Grant/research support from: Pfizer, Abbvie, Consultant of: Pfizer, AbbVie, Roche, Lilly, Novartis

AB0820 COMPARATIVE EFFICACY OF GUSELKUMAB IN PATIENTS WITH PSORIATIC ARTHRITIS: RESULTS FROM SYSTEMATIC LITERATURE REVIEW AND NETWORK META-ANALYSIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1713-1714
Author(s):  
I. Mcinnes ◽  
P. J. Mease ◽  
K. Eaton ◽  
A. Schubert ◽  
S. Peterson ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Literature Review ◽  
Adverse Events ◽  
Systematic Literature Review ◽  
Targeted Therapies ◽  
Meta Analysis ◽  
Tumor Necrosis Factor Inhibitor ◽  
Forest Plot ◽  
Research Support ◽  
Phase 3

Background:The efficacy of the interleukin (IL)-23 subunit p19 inhibitor guselkumab (GUS) for psoriatic arthritis (PsA) has recently been demonstrated in two Phase 3 trials (DISCOVER-1 & -2) but has not been evaluated versus existing targeted therapies for PsA.Objectives:To compare GUS to targeted therapies for PsA through network meta-analysis (NMA).Methods:A systematic literature review was performed to identify PsA randomized controlled trials from 2000 to 2018. Bayesian NMAs were performed to compare treatments on American College of Rheumatology (ACR) 20/50/70 response, Psoriasis Area Severity Index (PASI) 75/90/100 response, Health Assessment Questionnaire Disability Index (HAQ-DI) score, resolution of enthesitis (RoE), resolution of dactylitis (RoD), adverse events (AEs) and serious adverse events (SAEs). Analyses used random effects models that adjusted for placebo response via meta-regression on baseline risk when feasible. Results are summarized by ranking treatments according to median absolute probabilities of response derived from NMAs.Results:Twenty-six Phase 3 studies were included in the quantitative synthesis. Studies were placebo-controlled up to 24 weeks and evaluated 13 targeted therapies for PsA. Absolute probabilities are reported for PASI 90 & ACR 20 responses according toFigure 1,and a forest plot of relative risks versus placebo for AEs is reported according toFigure 2. For ACR 20 response, GUS 100 mg every 4 weeks (Q4W) and every 8 weeks (Q8W) ranked 5th and 8th out of 20 interventions and were comparable to IL-17A inhibitor (IL-17Ai) and most tumor necrosis factor inhibitor (TNFi) agents. Similar findings were observed for ACR 50 and 70 responses. For PASI 90 response, GUS Q4W and Q8W ranked 1st and 2nd out of 15 interventions and were highly likely to provide a greater benefit than most other agents. Similar findings were observed for PASI 75 and 100 responses. For HAQ-DI score, GUS Q4W and Q8W ranked 6th and 10th out of 20 interventions and were comparable to IL-17Ai and most TNFi agents. For RoE, GUS Q4W and Q8W ranked 8th and 6th out of 13 interventions and were comparable to IL-17Ai and TNFi agents. For RoD, GUS Q4W and Q8W ranked 8th and 9th out of 13 interventions and were comparable to most IL-17Ai and TNFi agents. For AEs, GUS Q4W and Q8W ranked 3rd and 2nd out of 19 interventions and were comparable to IL-17Ai and TNFi agents. Likewise, for SAEs, GUS Q4W and Q8W ranked 4th and 5th out of 20 interventions and were comparable to IL-17Ai and TNFi agents. Analyses that controlled for previous exposure to biologics or assessed outcomes at alternative timepoints were broadly consistent with primary analysis results.Conclusion:NMA results indicate that GUS is comparable to most targeted PsA treatments for improvement in arthritis, soft tissue damage, physical function, and safety outcomes. For PASI outcomes, GUS is highly likely to provide a greater benefit than other targeted PsA treatments.Disclosure of Interests:Iain McInnes Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, Novartis, Pfizer, and UCB, Philip J Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/research support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau, Kiefer Eaton Shareholder of: Test Pharma, Consultant of: Janssen, Agata Schubert Employee of: Janssen-Cilag, Steve Peterson Employee of: Janssen Research & Development, LLC, Tim Disher Consultant of: Janssen, Wim Noel Employee of: Janssen Pharmaceuticals NV, Hassan Fareen Employee of: Janssen, Chetan Karyekar Shareholder of: Johnson & Johnson, Consultant of: Janssen, Employee of: Janssen Global Services, LLC. Previously, Novartis, Bristol-Myers Squibb, and Abbott Labs., Suzy Van Sanden Employee of: Janssen, Christopher T. Ritchlin Grant/research support from: UCB Pharma, AbbVie, Amgen, Consultant of: UCB Pharma, Amgen, AbbVie, Lilly, Pfizer, Novartis, Gilead, Janssen, Wolf-Henning Boehncke Grant/research support from: Janssen Research & Development, LLC, Consultant of: Janssen

scholarly journals Evidence for cannabis and cannabinoids for epilepsy: a systematic review of controlled and observational evidence

2018 ◽  
Vol 89 (7) ◽  
pp. 741-753 ◽  
Author(s):  
Emily Stockings ◽  
Dino Zagic ◽  
Gabrielle Campbell ◽  
Megan Weier ◽  
Wayne D Hall ◽  
...  
Keyword(s):  
Adverse Events ◽  
Seizure Frequency ◽  
Observational Studies ◽  
Number Needed To Treat ◽  
Seizure Freedom ◽  
Low Grade ◽  
Serious Adverse Events ◽  
Seizure Reduction ◽  
Increased Risk ◽  
Randomised Controlled

Review evidence for cannabinoids as adjunctive treatments for treatment-resistant epilepsy. Systematic search of Medline, Embase and PsycINFO was conducted in October 2017. Outcomes were: 50%+ seizure reduction, complete seizure freedom; improved quality of life (QoL). Tolerability/safety were assessed by study withdrawals, adverse events (AEs) and serious adverse events (SAEs). Analyses were conducted in Stata V.15.0. 36 studies were identified: 6 randomised controlled trials (RCTs), 30 observational studies. Mean age of participants was 16.1 years (range 0.5–55 years). Cannabidiol (CBD) 20 mg/kg/day was more effective than placebo at reducing seizure frequency by 50%+(relative risk (RR) 1.74, 95% CI 1.24 to 2.43, 2 RCTs, 291 patients, low Grades of Recommendation, Assessment, Development and Evaluation (GRADE) rating). The number needed to treat for one person using CBD to experience 50%+ seizure reduction was 8 (95% CI 6 to 17). CBD was more effective than placebo at achieving complete seizure freedom (RR 6.17, 95% CI 1.50 to 25.32, 3 RCTs, 306 patients, low GRADE rating), and improving QoL (RR 1.73, 95% CI 1.33 to 2.26), however increased risk of AEs (RR 1.24, 95% CI 1.13 to 1.36) and SAEs (RR 2.55, 95% CI 1.48 to 4.38). Pooled across 17 observational studies, 48.5% (95% CI 39.0% to 58.1%) of patients reported 50%+ reductions in seizures; in 14 observational studies 8.5% (95% CI 3.8% to 14.5%) were seizure-free. Twelve observational studies reported improved QoL (55.8%, 95% CI 40.5 to 70.6); 50.6% (95% CI 31.7 to 69.4) AEs and 2.2% (95% CI 0 to 7.9) SAEs. Pharmaceutical-grade CBD as adjuvant treatment in paediatric-onset drug-resistant epilepsy may reduce seizure frequency. Existing RCT evidence is mostly in paediatric samples with rare and severe epilepsy syndromes; RCTs examining other syndromes and cannabinoids are needed.PROSPERO registration numberCRD42017055412.

scholarly journals Influence of Immunogenicity on the Efficacy of Long-Term Treatment with TNFαBlockers in Rheumatoid Arthritis and Spondyloarthritis Patients

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Inesa Arstikyte ◽  
Giedre Kapleryte ◽  
Irena Butrimiene ◽  
Algirdas Venalis
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Events ◽  
Clinical Characteristics ◽  
Term Treatment ◽  
High Serum ◽  
Treatment Discontinuation ◽  
Increased Risk ◽  
Long Term Treatment ◽  
Biologic Drug

Objective. To analyze the clinical relevance of the levels of TNFαblockers and anti-drug antibodies (anti-drug Ab) in patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA) treated with adalimumab (ADA), etanercept (ETA), or infliximab (INF) for a prolonged period of time.Methods. Clinical characteristics (disease activity, and adverse events), serum TNFαblockers, and anti-drug Ab levels were evaluated in 62 RA and 81 SpA patients treated with TNFαblockers for a median of 28 months.Results. Anti-ADA Ab were detected in 1 (4.0%) and anti-INF Ab in 14 out of 57 (24.6%) RA and SpA patients. Patient with anti-ADA Ab and 57.1% patients with anti-INF Ab were considered nonresponders to treatment. Anti-ETA Ab were not found in any of 61 ETA treated patients. Anti-ADA and anti-INF Ab levels differ between responders and nonresponders(P>0.05). Three (5.3%) patients with high serum anti-INF Ab levels developed infusion related reactions. Patients with anti-INF Ab more often required changing to another biologic drug (OR 11.43 (95% CI 1.08–120.93)) and treatment discontinuation (OR 9.28 (95% CI 1.64–52.52)).Conclusion. Patients not responding to treatment had higher serum anti-ADA and anti-INF Ab concentrations. Anti-INF Ab formation is related to increased risk of infusion related reactions, changing to another biologic drug, and treatment discontinuation.

scholarly journals SAT0064 VACCINATION RATE AND RISK FACTORS FOR NON-VACCINATION IN RHEUMATOID ARTHRITIS: A CROSS-SECTIONAL PROSPECTIVE MULTICENTRIC OBSERVATIONAL STUDY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 965.2-965
Author(s):  
C. Rempenault ◽  
T. Barnetche ◽  
M. Magnol ◽  
B. Castagne ◽  
M. Pugibet ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Observational Study ◽  
Vaccination Rate ◽  
University Hospitals ◽  
Research Support ◽  
Cross Sectional ◽  
Vaccination Rates ◽  
Increased Risk ◽  
Chi Squared ◽  
Patient’S Information

Background:Rheumatoid arthritis (RA) patients are at increased risk of infections, some of which could be prevented in part by vaccination (1). Influenza and pneumococcal vaccines are recommended in RA (2). However, vaccination coverage of these patients remains very low. Five years ago, we found in a previous study that vaccination rates in France were 55% for pneumococcal and 60% for influenza vaccines (3).Objectives:The aim of our study was to evaluate the vaccination rate among RA patients, compare it with our previous results, and identify factors associated with non-vaccination.Methods:We conducted a cross sectional multicentric observational study in the rheumatology departments of 5 university hospitals in France. Data were collected from December 2018 to July 2019. Outpatients and hospitalized adult patients with RA according to the ACR/EULAR 2010 criteria were included. Data were collected during a single visit through an anonymous questionnaire completed by the patients. Pearson Chi-squared analysis and multivariable logistic regression were used to compare characteristics of vaccinated versus non vaccinated patients.Results:584 patients (77.9% of women, mean age 61.8±12.6 years old) were included. 81.7% were RF and/or ACPA positive, with a mean RA duration of 15.7±10.5 years, 58.2% were treated with methotrexate (MTX), and 68.6% with a biologic. Vaccination rate against pneumococcal was 78.9% (versus 55% in 2013, p<0.0001) and 60.4% for influenza (versus 60% in 2013). The main reason for non-vaccination was absence of vaccine proposal (59.2%) for pneumococcal, and fear of vaccines (56.7%) for influenza. In the multivariate analysis, a higher level of education (OR [CI95] 4.4 [2.3-8.4], p<0.0001), a very good opinion on vaccination (2.1 [1.1-4.1], p=0.003), vaccination against influenza done (2.3 {1.3-4.2], p=0.006), and exposure to biologics (4.0 [2.2-7.4], p<0.0001) were associated with vaccination against pneumococcal. Age over 65 years old (2.0 [1.2-3.2], p=0.006), participation in a patients’ association (3.6 [1.4-8.9], p=0.006), vaccination against pneumococcal done (2.4 [1.3-4.5], p=0.004), exposure to biologics (2.1 [1.2-3.7], p=0.006), a good (3.3 [1.4-8.9], p=0.03) and a very good opinion on vaccination (6.6 [2.8-15.6], p<0.0001) were associated with vaccination against influenza.Conclusion:Vaccination rate against pneumococcal increased over the last 5 years but remained stable for influenza vaccine in French RA patients. This could be improved with patient’s information and education, especially in patients age under 65, biologic naïve and with a bad opinion about vaccination.References:[1] Doran MF, Crowson CS et al. Arthritis Rheum. 2002 Sep;46(9):2287–93.[2]van Assen S, Agmon-Levin N et al. Ann Rheum Dis. 2011 Mar;70(3):414–22.[3] Hua C, Morel J et al. Rheumatol Oxf Engl. 2015 Apr;54(4):748–50.Disclosure of Interests:Claire Rempenault: None declared, Thomas Barnetche: None declared, Marion Magnol: None declared, Benjamin Castagne: None declared, marine pugibet: None declared, Eleonore Berard: None declared, Marie-Elise Truchetet: None declared, Pascale Vergne-Salle: None declared, Anne Tournadre: None declared, Adeline Ruyssen-Witrand Grant/research support from: Abbvie, Pfizer, Consultant of: Abbvie, BMS, Lilly, Mylan, Novartis, Pfizer, Sandoz, Sanofi-Genzyme, Cédric Lukas: None declared

scholarly journals Laboratory and clinical adverse events following initiation of dimethyl fumerate

2015 ◽  
Vol 42 (S1) ◽  
pp. S9-S9
Author(s):  
YM Al Malik ◽  
J Greenfield ◽  
W Wall ◽  
LM Metz
Keyword(s):  
Side Effects ◽  
Adverse Events ◽  
Real World ◽  
Clinical Setting ◽  
Liver Enzymes ◽  
First Line Therapy ◽  
Elevated Liver Enzymes ◽  
Relapsing Remitting ◽  
Treatment Naïve ◽  
Relapsing Remitting Multiple Sclerosis

Background: Dimethyl fumerate (DF) is a first line therapy for relapsing remitting multiple sclerosis (RRMS). This retrospective cohort study aims to determine adverse events (AEs) after initiation of DF in a real world clinical setting. Methods: Data from patients at the Calgary MS Clinic with RRMS who initiated DF between July 1, 2013 and December 31, 2014 were analyzed. Demographic, clinical and lab information were collected from patient electronic medical records and the clinic database. Results: This analysis included 170 patients. At treatment initiation mean age was 42.1 years, 75% were women, mean disease duration was 12.5 years, median EDSS was 2.0, and 24% were treatment naïve. Median follow-up was 6.4 months (range: 1.5-17.7). AEs occurred in 101 (59%); the most common were flushing (31%), gastrointestinal (GI) side effects (24%), and elevated liver enzymes (18%). Other less frequent AEs included lymphopenia (lymphocyte count < 0.5) (4%) and proteinuria (4%). DF was discontinued by 17 (10%); median time to discontinuation was 3.1 months. Fifteen (9%) discontinued due to AE. Conclusions: AE associated with DF in a real world clinical setting is comparable to the Canadian monograph for flushing, GI side effects, and lymphopenia but lower for elevated liver enzymes and proteinuria.

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