scholarly journals The Use of Tocilizumab in Combination with Methotrexate in Indonesian Rheumatoid Arthritis Patients (PICTURE INA Study)

2018 ◽  
Vol 10 (1) ◽  
Author(s):  
Bambang Setyohadi ◽  
Harry Isbagio ◽  
Rachmat Gunadi Wachjudi ◽  
Joewono Soeroso ◽  
Handono Kalim ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Events ◽  
Disease Activity ◽  
Severe Disease ◽  
Inadequate Response ◽  
Das28 Score ◽  
Serious Adverse Events ◽  
Biologic Dmards ◽  
Low Disease Activity ◽  
Study Visit

Background Aim of this research is to assess the efficacy and safety of tocilizumab (TCZ) in combination with methotrexate (MTX) in Indonesian patients with moderate to severe active rheumatoid arthritis (RA) who have an inadequate response to non-biologic DMARDs.Methods This was a interventional, prospective, single arm, multicenter, study in  Indonesian male or female patients aged ≥ 18 years old, with a diagnosis of RA for > 6 months based on ACR 1987 revised criteria with moderate to severe disease activity (DAS28 score > 3.2) after ≥ 12 weeks of non-biologic DMARDs treatment. The treatment consisted of tocilizumab, 8 mg/kg, intravenous (IV), every 4 weeks for a total of 6 infusion in combination with oral MTX (10−25 mg) every week. Efficacy was assessed based on the percentage of patients achieving low disease activity state (DAS28 < 3.2), percentage of patients achieving reduction > 1.2 point of DAS28, percentage of patients achieving remission (DAS28 < 2.6), and percentage of patients with ACR20, ACR50, and ACR70 responses. Descriptive statistics will be used for presentation of results.Results 100% patients reached low disease activity (DAS28 ≤ 3.2) at last study visit (week 24) and clinically significant improvement (reduction at least 1.2 units) at every visit in DAS28, both for ITT or PP patients. Remission (DAS28 < 2.6) was observed in 82.1% (ITT patients) and 93.1 % (PP patients) on last study visit. ACR20, ACR50, and ACR70 were achieved in 20%, 34%, and 34% (ITT patients), and 7%, 24%, and 62% (PP patients) on week 24. There were 3 out of 39 patients (7.69%) with adverse events (AE) and serious adverse events (SAE) that resulted in discontinuation of TCZ treatment, consisting of 1 patient with SAE of sepsis ec acquired community pneumonia, 1 patient with SAE of pneumonia tuberculosis, and 1 patient with AE of candidiasis. Most common adverse events were hepatic dysfunction (30.7%), hypercholesterolemia (23.1%), followed by arthralgia (20.5%) Twelve percent of patients needed dose modification due to elevated liver enzyme (elevated ALT/SGPT level).Conclusion Tocilizumab seems to be efficacious and likely to have good safety profile in non- biologic DMARD nonresponsive RA patients of PICTURE INA study.   Keywords: Rheumatoid Arthritis, Tocilizumab, DMARD, DAS28

scholarly journals The Use of Tocilizumab in Combination with Methotrexate in Indonesian Rheumatoid Arthritis Patients (PICTURE INA Study)

2018 ◽  
Vol 10 (1) ◽  
Author(s):  
Bambang Setyohadi ◽  
Harry Isbagio ◽  
Rachmat Gunadi Wachjudi ◽  
Joewono Soeroso ◽  
Handono Kalim ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Events ◽  
Disease Activity ◽  
Severe Disease ◽  
Inadequate Response ◽  
Das28 Score ◽  
Serious Adverse Events ◽  
Biologic Dmards ◽  
Low Disease Activity ◽  
Study Visit

Background Aim of this research is to assess the efficacy and safety of tocilizumab (TCZ) in combination with methotrexate (MTX) in Indonesian patients with moderate to severe active rheumatoid arthritis (RA) who have an inadequate response to non-biologic DMARDs.Methods This was a interventional, prospective, single arm, multicenter, study in  Indonesian male or female patients aged ≥ 18 years old, with a diagnosis of RA for > 6 months based on ACR 1987 revised criteria with moderate to severe disease activity (DAS28 score > 3.2) after ≥ 12 weeks of non-biologic DMARDs treatment. The treatment consisted of tocilizumab, 8 mg/kg, intravenous (IV), every 4 weeks for a total of 6 infusion in combination with oral MTX (10−25 mg) every week. Efficacy was assessed based on the percentage of patients achieving low disease activity state (DAS28 < 3.2), percentage of patients achieving reduction > 1.2 point of DAS28, percentage of patients achieving remission (DAS28 < 2.6), and percentage of patients with ACR20, ACR50, and ACR70 responses. Descriptive statistics will be used for presentation of results.Results 100% patients reached low disease activity (DAS28 ≤ 3.2) at last study visit (week 24) and clinically significant improvement (reduction at least 1.2 units) at every visit in DAS28, both for ITT or PP patients. Remission (DAS28 < 2.6) was observed in 82.1% (ITT patients) and 93.1 % (PP patients) on last study visit. ACR20, ACR50, and ACR70 were achieved in 20%, 34%, and 34% (ITT patients), and 7%, 24%, and 62% (PP patients) on week 24. There were 3 out of 39 patients (7.69%) with adverse events (AE) and serious adverse events (SAE) that resulted in discontinuation of TCZ treatment, consisting of 1 patient with SAE of sepsis ec acquired community pneumonia, 1 patient with SAE of pneumonia tuberculosis, and 1 patient with AE of candidiasis. Most common adverse events were hepatic dysfunction (30.7%), hypercholesterolemia (23.1%), followed by arthralgia (20.5%) Twelve percent of patients needed dose modification due to elevated liver enzyme (elevated ALT/SGPT level).Conclusion Tocilizumab seems to be efficacious and likely to have good safety profile in non- biologic DMARD nonresponsive RA patients of PICTURE INA study.   Keywords: Rheumatoid Arthritis, Tocilizumab, DMARD, DAS28

Ml28133 -A Multicenter, Open-Label, Long-Term Extension Study of WA 19926 to Describe Safety During Treatment with Tocilizumab in Patients with Early, Moderate to Severe Rheumatoid Arthritis

2017 ◽  
Vol 71 (2) ◽  
pp. 83-90
Author(s):  
Irena Kafedziska ◽  
Snezhana Mishevska-Perchinkova ◽  
Dubravka Antova ◽  
Mimoza Kotevska Nikolova ◽  
Anzhelika Stojanovska ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Side Effects ◽  
Disease Activity ◽  
Clinical Remission ◽  
Severe Disease ◽  
Activity Score ◽  
Open Label ◽  
Serious Adverse Events ◽  
Biologic Dmards

Abstract Introduction. Biologic DMARDs (Disease Modifying Anti Rheumatic Drugs) have shown to be effective in the treatment of rheumatoid arthritis (RA) resistant to the use of synthetic DMARDs. The primary goal of this study wasto assess the long-term safety of the use of tocilizumab in patients with early rheumatoid arthritis, moderate to severe disease activity. The secondary goal was to assess the efficiency of tocilizumab in achieving and maintaining clinical remission of the disease. Methods. ML28133 is a long-term, extended study of 13 patients with rheumatoid arthritis treated with tocilizumab. Two patients were male (15.4%), 11(84.61%) female. The average age of patients was 53.27+/−10.68. Patients received 8mg/kg tocilizumab i.v. every four weeks, 104 weeks overall. Safety was assessed following side effects, blood tests, physical examination and vital signs. Efficiency was assessed by achieving and maintaining clinical remission according to DAS28 (Disease Activity Score 28), global assessment of disease activity, VAS score and HAQ-DI (Health Activity Score) questionnaire. Results. Incidence of side effects was 76.92%. Infections were of special interest and were most common (15.3%). Four patients had serious adverse events, three of which associated with tocilizumab, and therapy was stopped. In 11 (84.6%) of the 13 treated patients clinical remission was achieved at times. At the end of the study, 8 out of 9 patients were in remission. Conclusion. The results have shown significant therapeutic effect of tocilizumab even in the most severe forms of the disease, which gives hope for its use as a monotherapy.

scholarly journals POS0647 EFFICACY, SAFETY AND CHARACTERISTICS OF IGURATIMOD-BASED THERAPY IN THE TREATMENT OF UA, ERA AND RA PATIENTS FOR 24 WEEKS: A PROSPECTIVE COHORT STUDY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 561.2-562
Author(s):  
X. Liu ◽  
Z. Sun ◽  
W. Guo ◽  
F. Wang ◽  
L. Song ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cohort Study ◽  
Adverse Events ◽  
Disease Activity ◽  
Prospective Cohort Study ◽  
Early Rheumatoid Arthritis ◽  
Prospective Cohort ◽  
Combined Treatment ◽  
Serious Adverse Events

Background:Experts emphasize early diagnosis and treatment in RA, but the widely used diagnostic criterias fail to meet the accurate judgment of early rheumatoid arthritis. In 2012, Professor Zhanguo Li took the lead in establishing ERA “Chinese standard”, and its sensitivity and accuracy have been recognized by peers. However, the optimal first-line treatment of patients (pts) with undifferentiated arthritis (UA), early rheumatoid arthritis (ERA), and rheumatoid arthritis (RA) are yet to be established.Objectives:To evaluate the efficacy and safety of Iguratimod-based (IGU-based) Strategy in the above three types of pts, and to explore the characteristics of the effects of IGU monotherapy and combined treatment.Methods:This prospective cohort study (ClinicalTrials.gov Identifier NCT01548001) was conducted in China. In this phase 4 study pts with RA (ACR 1987 criteria[1]), ERA (not match ACR 1987 criteria[1] but match ACR/EULAR 2010 criteria[2] or 2014 ERA criteria[3]), UA (not match classification criteria for ERA and RA but imaging suggests synovitis) were recruited. We applied different treatments according to the patient’s disease activity at baseline, including IGU monotherapy and combination therapies with methotrexate, hydroxychloroquine, and prednisone. Specifically, pts with LDA and fewer poor prognostic factors were entered the IGU monotherapy group (25 mg bid), and pts with high disease activity were assigned to combination groups. A Chi-square test was applied for comparison. The primary outcomes were the proportion of pts in remission (REM)or low disease activity (LDA) that is DAS28-ESR<2.6 or 3.2 at 24 weeks, as well as the proportion of pts, achieved ACR20, Boolean remission, and good or moderate EULAR response (G+M).Results:A total of 313 pts (26 pts with UA, 59 pts with ERA, and 228 pts with RA) were included in this study. Of these, 227/313 (72.5%) pts completed the 24-week follow-up. The results showed that 115/227 (50.7%), 174/227 (76.7%), 77/227 (33.9%), 179/227 (78.9%) pts achieved DAS28-ESR defined REM and LDA, ACR20, Boolean remission, G+M response, respectively. All parameters continued to decrease in all pts after treatment (Fig 1).Compared with baseline, the three highest decline indexes of disease activity at week 24 were SW28, CDAI, and T28, with an average decline rate of 73.8%, 61.4%, 58.7%, respectively. Results were similar in three cohorts.We performed a stratified analysis of which IGU treatment should be used in different cohorts. The study found that the proportion of pts with UA and ERA who used IGU monotherapy were significantly higher than those in the RA cohort. While the proportion of triple and quadruple combined use of IGU in RA pts was significantly higher than that of ERA and UA at baseline and whole-course (Fig 2).A total of 81/313 (25.8%) pts in this study had adverse events (AE) with no serious adverse events. The main adverse events were infection(25/313, 7.99%), gastrointestinal disorders(13/313, 4.15%), liver dysfunction(12/313, 3.83%) which were lower than 259/2666 (9.71%) in the previous Japanese phase IV study[4].The most common reasons of lost follow-up were: 1) discontinued after remission 25/86 (29.1%); 2) lost 22/86 (25.6%); 3) drug ineffective 19/86 (22.1%).Conclusion:Both IGU-based monotherapy and combined therapies are tolerant and effective for treating UA, ERA, and RA, while the decline in joint symptoms was most significant. Overall, IGU combination treatments were most used in RA pts, while monotherapy was predominant in ERA and UA pts.References:[1]Levin RW, et al. Scand J Rheumatol 1996, 25(5):277-281.[2]Kay J, et al. Rheumatology 2012, 51(Suppl 6):vi5-9.[3]Zhao J, et al. Clin Exp Rheumatol 2014, 32(5):667-673.[4]Mimori T, et al. Mod Rheumatol 2019, 29(2):314-323.Disclosure of Interests:None declared

scholarly journals Subcutaneous Abatacept for the Treatment of Rheumatoid Arthritis: Longterm Data from the ACQUIRE Trial

2014 ◽  
Vol 41 (4) ◽  
pp. 629-639 ◽  
Author(s):  
Mark C. Genovese ◽  
César Pacheco Tena ◽  
Arturo Covarrubias ◽  
Gustavo Leon ◽  
Eduardo Mysler ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Severe Disease ◽  
Incidence Rates ◽  
Phase Iii ◽  
Inadequate Response ◽  
Open Label ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Safety And Efficacy ◽  
Link Type

Objective.Assess longterm tolerability, safety, and efficacy of subcutaneous (SC) abatacept (ABA) in methotrexate-refractory patients with rheumatoid arthritis (RA).Methods.The phase III, multinational Abatacept Comparison of Sub[QU]cutaneous Versus Intravenous in Inadequate Responders to MethotrexatE (ACQUIRE) trial comprised a 6-month, randomized, double-blind (DB) period, in which patients received intravenous (IV) or SC ABA, plus MTX, followed by an open-label, longterm extension (LTE), in which patients received SC ABA, 125 mg/week. Safety and efficacy from the LTE (∼3.5 yrs of exposure) are reported.Results.Patients who completed the DB period (1372/1385, 99.1%) entered the LTE; 1134 patients (82.7%) kept taking the treatment at time of reporting. Mean (SD) was 31.9 months (6.8); median (range) exposure was 33.0 (8–44) months. Patients entering the LTE had longstanding, moderate-to-severe disease [mean 7.6 (7.9) yrs and DAS28 (C-reactive protein) 6.2 (0.9)]. Incidence rates (events/100 patient-yrs) were reported for serious adverse events (8.76, 95% CI 7.71, 9.95), infections (44.80, 95% CI 41.76, 48.01), serious infections (1.72, 95% CI 1.30, 2.27), malignancies (1.19, 95% CI 0.86, 1.66), and autoimmune events (1.31, 95% CI 0.95, 1.79). Twenty-seven patients (2%) experienced injection-site reactions; all except 1 were mild. American College of Rheumatology 20, 50, and 70 responses achieved during the DB period were maintained through the LTE, and on Day 981 were 80.2% (95% CI 77.2, 83.2), 63.5% (95% CI 58.2, 68.9), and 39.5% (95% CI 34.0, 44.9) for patients who kept taking SC ABA, and 80.0% (95% CI 77.0, 83.0), 63.2% (95% CI 57.8, 68.7), and 39.2% (95% CI 33.7, 44.7) for those who switched from IV to SC ABA.Conclusion.These findings support SC ABA as a well-tolerated and efficacious longterm treatment for patients with RA and inadequate response to MTX (ClinicalTrials.gov identifier NCT00559585).

SAT0151 EFFICACY AND SAFETY OF UPADACITINIB VERSUS ABATACEPT IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS AND PRIOR INADEQUATE RESPONSE OR INTOLERANCE TO BIOLOGIC DISEASE-MODIFYING ANTI-RHEUMATIC DRUGS (SELECT-CHOICE): A DOUBLE-BLIND, RANDOMIZED CONTROLLED PHASE 3 TRIAL

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1015-1016
Author(s):  
A. Rubbert-Roth ◽  
J. Enejosa ◽  
A. Pangan ◽  
R. Xavier ◽  
B. Haraoui ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Study Drug ◽  
Signs And Symptoms ◽  
Drug Discontinuation ◽  
Inadequate Response ◽  
Research Support ◽  
Phase 3 ◽  
Double Blind ◽  
Biologic Dmards

Background:Upadacitinib (UPA) is an oral, reversible, selective JAK 1 inhibitor approved for the treatment of moderate to severe rheumatoid arthritis (RA). The efficacy/safety of UPA has been demonstrated in phase 3 studies, including superiority to adalimumab in patients (pts) with prior inadequate response (IR) to methotrexate.1-4Objectives:To assess the efficacy/safety of UPA vs abatacept (ABA) in pts with prior IR or intolerance to biologic DMARDs (bDMARDs).Methods:Pts were randomized to once daily UPA 15 mg or intravenous ABA (at Day 1, Weeks [Wks] 2, 4, 8, 12, 16 and 20 [< 60 kg: 500 mg; 60-100 kg: 750 mg; >100 kg: 1,000 mg]), with all pts continuing background stable csDMARDs. The study was double-blind for 24 wks. Starting at Wk 12, pts who did not achieve ≥20% improvement from baseline (BL) in both tender and swollen joint counts at two consecutive visits, had background medication(s) adjusted or initiated. The primary endpoint was change from BL in DAS28(CRP) at Wk 12 (non-inferiority). The non-inferiority of UPA vs ABA was tested using the 95% CI of treatment difference against a non-inferiority margin of 0.6. The two key secondary endpoints at Wk 12 were change from BL in DAS28(CRP) and the proportion of pts achieving clinical remission (CR) based on DAS28(CRP), defined as DAS28(CRP) <2.6. Both endpoints were to demonstrate the superiority of UPA vs. ABA. Treatment-emergent adverse events (TEAEs) are reported up to Wk 24 for all pts who received at least one dose of study drug.Results:Of 612 pts treated; 67% of pts had received 1 prior bDMARD, 22% received 2 prior bDMARDs, and 10% received ≥ 3 prior bDMARDs. 549 (90%) completed 24 wks of treatment. Common reasons for study drug discontinuation were AEs (UPA, 3.6%; ABA, 2.6%) and withdrawal of consent (UPA, 1.7%; ABA, 2.6%).Non-inferiority and superiority were met for UPA vs ABA at Wk 12 for change from BL in DAS28(CRP) (-2.52 vs -2.00; -0.52 [-0.69, -0.35]; p <0.001 for UPA vs ABA). UPA also demonstrated superiority to ABA in achieving DAS28(CRP) <2.6 (30.0% vs 13.3%; p <0.001 for UPA vs ABA; Figure 1). Improvements in disease activity and remission rates were maintained through Wk 24. The proportions of pts achieving low disease activity (defined as DAS28(CRP) ≤3.2), ACR20, ACR50, and ACR70 responses were greater with UPA compared with ABA at Wk 12 (nominal p <0.05). More stringent outcome measures – CR, ACR50, and ACR70 responses - remained higher with UPA than ABA through Wk 24 (nominal p <0.05). Incidence of serious TEAEs, AEs leading to discontinuation, hepatic disorders, and CPK elevations were numerically higher with UPA versus ABA (Figure 2). Eight cases of herpes zoster were reported (4 in each treatment arm). No malignancies were reported. One case of adjudicated MACE, two adjudicated cases of VTE (1 pt with DVT and 1 pt with PE; both pts had at least one risk factor for VTE), and one treatment-emergent death were reported with UPA.Conclusion:In RA pts with a prior IR or intolerance to bDMARDs, UPA demonstrated superior improvement in signs and symptoms vs ABA based on change in DAS28(CRP) and in achieving CR at Wk 12. The safety profile of UPA was consistent with the phase 3 RA studies with no new risks identified.References:[1]Burmester GR, et al. Lancet. 2018;391(10139):2503-12[2]Fleischmann R, et al. Arthritis Rheumatol. 2019;71(11):1788-800[3]Genovese MC, et al. Lancet. 2018;391(10139):2513-24[4]Smolen JS, et al. Lancet. 2019;393(10188):2303-11Disclosure of Interests:Andrea Rubbert-Roth Consultant of: Abbvie, BMS, Chugai, Pfizer, Roche, Janssen, Lilly, Sanofi, Amgen, Novartis, Jeffrey Enejosa Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Aileen Pangan Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Ricardo Xavier Consultant of: AbbVie, Pfizer, Novartis, Janssen, Eli Lilly, Roche, Boulos Haraoui Grant/research support from: Abbvie, Amgen, Pfizer, UCB, Grant/research support from: AbbVie, Amgen, BMS, Janssen, Pfizer, Roche, and UCB, Consultant of: Abbvie, Amgen, Lilly, Pfizer, Sandoz, UCB, Consultant of: AbbVie, Amgen, BMS, Celgene, Eli Lilly, Janssen, Merck, Pfizer, Roche, and UCB, Speakers bureau: Pfizer, Speakers bureau: Amgen, BMS, Janssen, Pfizer, and UCB, Maureen Rischmueller Consultant of: Abbvie, Bristol-Meyer-Squibb, Celgene, Glaxo Smith Kline, Hospira, Janssen Cilag, MSD, Novartis, Pfizer, Roche, Sanofi, UCB, Nasser Khan Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Ying Zhang Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Naomi Martin Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Mark C. Genovese Grant/research support from: Abbvie, Eli Lilly and Company, EMD Merck Serono, Galapagos, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, Pfizer Inc., RPharm, Sanofi Genzyme, Consultant of: Abbvie, Eli Lilly and Company, EMD Merck Serono, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, RPharm, Sanofi Genzyme

Patients with Moderate Rheumatoid Arthritis (RA) Achieve Better Disease Activity States with Etanercept Treatment Than Patients with Severe RA

2009 ◽  
Vol 36 (3) ◽  
pp. 522-531 ◽  
Author(s):  
EDWARD KEYSTONE ◽  
BRUCE FREUNDLICH ◽  
MICHAEL SCHIFF ◽  
JUAN LI ◽  
MICHELE HOOPER
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Clinical Outcomes ◽  
Radiographic Progression ◽  
Severe Disease ◽  
High Dose ◽  
Etanercept Treatment ◽  
Low Disease Activity ◽  
Moderate Disease ◽  
Das28 Remission

Objective.This analysis examined clinical and radiographic responses to methotrexate (MTX), etanercept (ETN), and combination ETN and MTX in patients with moderate versus severe rheumatoid arthritis (RA) in both early and late disease.Methods.Data from the Trial of Etanercept and Methotrexate With Radiographic Patient Outcomes (TEMPO) and the Early Rheumatoid Arthritis trials were used. Patients were classified with moderate or severe RA based on Disease Activity Score including 28-joint count (DAS28). Outcomes included DAS28 remission, DAS28 low disease activity, Health Assessment Questionnaire (HAQ), American College of Rheumatology (ACR) scores, Total Sharp Score (TSS) progression, no radiographic progression (annualized change in TSS ≥ 0), change from baseline in TSS, and the change in TSS for patients who had radiographic progression (TSS > 0).Results.Patients with moderate disease generally achieved better clinical outcomes than patients with severe disease, including significant differences in DAS28 remission, low disease activity, and HAQ ≤0.5 at Month 12. Patients with baseline severe disease had higher ACR and DAS responses than patients with moderate disease.Conclusion.Patients with severe RA disease activity achieved substantial clinical improvement with high-dose MTX and/or ETN treatment, but patients with moderate disease were more likely to reach a lower disease activity state. These findings were independent of disease duration. The results support the opportunity for excellent clinical outcomes, particularly with combination therapy, in patients with moderate RA.

scholarly journals Baricitinib in patients with inadequate response or intolerance to conventional synthetic DMARDs: results from the RA-BUILD study

2016 ◽  
Vol 76 (1) ◽  
pp. 88-95 ◽  
Author(s):  
Maxime Dougados ◽  
Désirée van der Heijde ◽  
Ying-Chou Chen ◽  
Maria Greenwald ◽  
Edit Drescher ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Event ◽  
Adverse Events ◽  
Disease Activity ◽  
Joint Damage ◽  
Janus Kinase ◽  
Phase Iii ◽  
Inadequate Response ◽  
Acr20 Response ◽  
Synthetic Dmards

BackgroundBaricitinib is an oral, reversible, selective Janus kinase 1 and 2 inhibitor.MethodsIn this phase III, double-blind 24-week study, 684 biologic disease-modifying antirheumatic drug (DMARD)-naïve patients with rheumatoid arthritis and inadequate response or intolerance to ≥1 conventional synthetic DMARDs were randomly assigned 1:1:1 to placebo or baricitinib (2 or 4 mg) once daily, stratified by region and the presence of joint erosions. Endpoint measures included American College of Rheumatology 20% response (ACR20, primary endpoint), Disease Activity Score (DAS28) and Simplified Disease Activity Index (SDAI) score ≤3.3.ResultsMore patients achieved ACR20 response at week 12 with baricitinib 4 mg than with placebo (62% vs 39%, p≤0.001). Compared with placebo, statistically significant improvements in DAS28, SDAI remission, Health Assessment Questionnaire-Disability Index, morning joint stiffness, worst joint pain and worst tiredness were observed. In a supportive analysis, radiographic progression of structural joint damage at week 24 was reduced with baricitinib versus placebo. Rates of adverse events during the treatment period and serious adverse events (SAEs), including serious infections, were similar among groups (SAEs: 5% for baricitinib 4 mg and placebo). One patient had an adverse event of tuberculosis (baricitinib 4 mg); one patient had an adverse event of non-melanoma skin cancer (baricitinib 4 mg). Two deaths and three major adverse cardiovascular events occurred (placebo). Baricitinib was associated with a decrease in neutrophils and increases in low-density and high-density lipoprotein.ConclusionsIn patients with rheumatoid arthritis and an inadequate response or intolerance to conventional synthetic DMARDs, baricitinib was associated with clinical improvement and inhibition of progression of radiographic joint damage.Trial registration numberNCT01721057; Results.

Tocilizumab for Rheumatoid Arthritis: A Cochrane Systematic Review

2010 ◽  
Vol 38 (1) ◽  
pp. 10-20 ◽  
Author(s):  
JASVINDER A. SINGH ◽  
SABA BEG ◽  
MARIA ANGELES LOPEZ-OLIVO
Keyword(s):  
Rheumatoid Arthritis ◽  
Systematic Review ◽  
Adverse Event ◽  
Adverse Events ◽  
Disease Activity ◽  
Low Density Lipoprotein ◽  
Health Assessment ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Serious Adverse Events

Objective.To compare the benefit and safety of tocilizumab to placebo in patients with rheumatoid arthritis (RA).Methods.We searched multiple databases for published randomized or controlled clinical trials comparing benefit and safety of tocilizumab to placebo, disease-modifying antirheumatic drugs (DMARD), or other biologics. For dichotomous outcomes, we calculated the relative risk, and for continuous outcomes, the mean difference.Results.Eight randomized controlled trials were included in this systematic review, with 3334 participants, 2233 treated with tocilizumab and 1101 controls. The US and Canadian approved dose of tocilizumab, 8 mg/kg every 4 weeks, was given to 1561 participants. In patients taking concomitant methotrexate, compared to placebo, patients treated with approved dose of tocilizumab were substantially and statistically significantly more likely than placebo to achieve the American College of Rheumatology 50 (absolute percentage, 38.8% vs 9.6%, respectively; RR 3.2, 95% CI 2.7, 3.7); Disease Activity Score remission (30.5% vs 2.7%; RR 8.7, 95% CI 6.3, 11.8); and a clinically meaningful decrease in Health Assessment Questionnaire (HAQ)/Modified HAQ scores (60.5% vs 34%; RR 1.8, 95% CI 1.6, 1.9). There were no substantive statistically significant differences in serious adverse effects (0.8% vs 0.7%; RR 1.2, 95% CI 0.8, 1.6) or withdrawals due to adverse events (4.9% vs 3.7%; RR 1.4, 95% CI 0.9, 2.1); however, tocilizumab-treated patients were significantly more likely to have any adverse event (74% vs 65%; RR 1.05, 95% CI 1.03, 1.07); elevation in the ratio of low-density lipoprotein to high-density lipoprotein cholesterol (HDL; 20% vs 12%; RR 1.7, 95% CI 1.2, 2.2); and increase in the ratio of total to HDL cholesterol (12% vs 7%; RR 1.7, 95% CI 1.2, 2.6); and they were less likely to withdraw from treatment for any reason (8.1% vs 14.9%; RR 0.6, 95% CI 0.5, 0.8).Conclusion.At the approved dose of 8 mg/kg every 4 weeks, tocilizumab in combination with methotrexate/DMARD is beneficial in decreasing RA disease activity and improving function. Tocilizumab treatment was associated with a significant increase in cholesterol levels and occurrence of any adverse event, but not serious adverse events. Larger safety studies are needed to address these safety concerns.

scholarly journals Comparative effectiveness of biological medicines in rheumatoid arthritis: systematic review and network meta-analysis including aggregate results from reanalysed individual patient data

BMJ ◽  
2020 ◽  
pp. m2288 ◽  
Author(s):  
Kirsten Janke ◽  
Katharina Biester ◽  
Dietmar Krause ◽  
Bernd Richter ◽  
Christoph Schürmann ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Comparative Effectiveness ◽  
Individual Patient Data ◽  
Meta Analysis ◽  
Patient Data ◽  
The Other ◽  
Serious Adverse Events ◽  
Low Disease Activity ◽  
Clinical Study Reports

Abstract Objective To assess the comparative effectiveness of biological medicines in rheumatoid arthritis in sufficiently similar patient populations, based on the current definitions of key outcomes. Design Systematic review and network meta-analysis including aggregate results from reanalysed individual patient data. Data sources Clinical study reports and aggregate results from reanalyses of individual patient data on key outcomes for rheumatoid arthritis provided by study sponsors for studies conducted up to 2017, and several databases and registries from inception up to February 2017. Eligibility criteria for selecting studies Randomised controlled trials investigating patient relevant outcomes in adults with rheumatoid arthritis treated with biological medicines in combination with methotrexate after methotrexate failure for at least 24 weeks. Results 45 eligible trials were identified. Combining data from clinical study reports and aggregate results from reanalyses of individual patient data allowed extensive analyses yielding sufficiently similar populations and homogeneous study results for network meta-analyses, including up to 35 studies on eight biological medicines combined with methotrexate. These analyses showed few statistically significant differences between the combination treatments. For example, anakinra showed less benefit than almost all the other seven biological medicines regarding clinical remission or low disease activity (clinical disease activity index ≤2.8 or ≤10, respectively) and certolizumab pegol showed more harm than the other seven biological medicines regarding serious adverse events or infections. Some outcomes had very wide 95% confidence intervals, potentially implying unidentified differences between the eight biological medicines, but wide 95% confidence intervals were less prominent for low disease activity, serious adverse events, and infections. Owing to a lack of head-to-head trials, results were mainly based on indirect comparisons with a limited number of studies, and recently approved Janus kinase inhibitors could not be included. Conclusions For patients with rheumatoid arthritis after methotrexate failure, only minor differences in benefits and harms were seen between biological medicines in combination with methotrexate. However, the analysis was hampered by a lack of long term direct comparisons. The substantial information gain achieved by the reanalysis of individual patient data calls for the routine availability of individual patient data.

scholarly journals ADALIMUMAB DISCONTINUATION IN PATIENTS WITH RHEUMATOID ARTHRITIS AFTER ACHIEVING SUSTAINED REMISSION

2018 ◽  
Vol 56 (3) ◽  
pp. 316-320
Author(s):  
N. V. Demidova ◽  
E. A. Galushko ◽  
S. I. Glukhova ◽  
N. M. Savushkina ◽  
A. M. Satybaldyev ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Biological Agents ◽  
Sustained Remission ◽  
Serious Adverse Events ◽  
Low Disease Activity ◽  
Moderate Disease ◽  
Active Arthritis ◽  
Das28 Remission

Objective: to assess whether adalimumab (AD) can be gradually discontinued during continuous methotrexate (MTX) use in patients with early rheumatoid arthritis (ERA).Subjects and methods. Within the REMARCA (the Russian study of methotrexate and biological agents in early active arthritis) study, the investigators examined 20 patients (17 women and 3 men; median age, 51 [41.5; 56] years) with ERA (disease duration, 10 [5.5; 20] months; DAS28, 5.17 [4.37; 6.51]; 85% of the patients were seropositive for rheumatoid factor and 85% for anti-cyclic citrullinated peptide antibodies.Results and discussion. All the patients received subcutaneous MTX 25 mg/week. Twelve weeks after beginning therapy with MTX, due to its inefficiency, ADA was added according to the standard scheme. At week 24, the median DAS28 was 3.0 [1.65; 3.73]; 85% of the patients achieved remission or low disease activity. After 3 months of ADA therapy, high or moderate disease activity remained in 3 (15%) patients; median DAS28 was 4.4 [4.3; 6.1]; the drug was discontinued in them due to ineffective therapy. After 12-month follow-up, low DAS28 scores were observed in 5 (29.4%), DAS28 remission was in 12 (70.6%) of the 17 patients who continued ADA treatment; after 24 months, all the 17 patients were noted to have remission. After achieving sustained remission (≥ 6-month duration during ADA therapy), there was a carefully controlled reduction (titration) in the dose of ADA with its complete discontinuation, by maintaining remission at 36-month follow-up; the median DAS28 was 1.6 [1.4; 2.2]. During ADA treatment, one female patient developed pustular psoriasis and therefore the drug was discontinued at 24-month follow-up during the period of sustained remission. Other serious adverse events and tuberculosis cases were not recorded.Conclusion. Thus, the results of the study are indicative of the high clinical efficiency of the therapy. After ADA discontinuation, sustained remission can be maintained in patients with ERA and if they took biological agents early. 

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