scholarly journals Etanercept therapy in rheumatoid arthritis: Efficacy and safety

2013 ◽  
Vol 141 (7-8) ◽  
pp. 495-502
Author(s):  
Tatjana Ilic ◽  
Biljana Milic ◽  
Dejan Celic ◽  
Biljana Vuckovic ◽  
Igor Mitic
Keyword(s):  
Rheumatoid Arthritis ◽  
Joint Destruction ◽  
Life Quality ◽  
Activity Level ◽  
Inadequate Response ◽  
Efficacy And Safety ◽  
Etanercept Therapy ◽  
Acr20 Response ◽  
Clinically Significant ◽  
High Level

Introduction. Etanercept, tumor necrosis factor (TNF?) antagonist, lowers the disease activity level in patients with rheumatoid arthritis (RA), reduces joint destruction saving physical functions and improving life quality. Objective. The aim of this study was to establish efficacy and safety of etanercept in combination with disease modifying antirheumatic drugs (DMARDs) in the treatment of RA. Methods. To patients with active RA, who were on therapy with DMARD, etanercept was introduced in weekly doses of 50 mg, with continuation of DMARD. Efficacy of this form of treatment was evaluated in the 12th week. Maintenance of the effect of treatment was also evaluated during 24, 48 and 96 weeks. Long term evaluation of etanercept safety was assessed by registering all unwanted events during a two year period. Results. After 12 weeks of treatment with etanercept, 80% of patients had ACR20 response, while 85% showed clinically significant decrease of DAS28 index. We achieved remission in five patients (12.5%) and low activity of RA in 17 patients (42.5%). During a 96week of followup period, achieved therapy effects were maintained. In four patients (10%) etanercept therapy was interrupted after 24 weeks because of inadequate response. In one of them (2.5%) we recorded a cardiovascular incident. Acute infections were registered in 47 cases. Four of those were severe infections. Neither cases of malignancy development were noted, nor were there any lethal disease outcomes. Conclusion. Etanercept in combination with DMARD shows a high level of efficacy in the treatment of RA. The safety profile of the drug is satisfactory.

SAT0136 RELATIVE EFFICACY AND SAFETY OF TOFACITINIB, BARICITINIB, UPADACITINIB, AND FILGOTINIB, IN COMPARISON WITH ADALIMUMAB IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS: A BAYESIAN NETWORK META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1005.1-1005
Author(s):  
Y. H. Lee ◽  
G. G. Song
Keyword(s):  
Rheumatoid Arthritis ◽  
Active Rheumatoid Arthritis ◽  
Response Rate ◽  
Meta Analysis ◽  
Inadequate Response ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Acr20 Response ◽  
Randomized Controlled ◽  
Acr20 Response Rate

Background:Methotrexate (MTX), an effective disease-modifying antirheumatic drug (DMARD) [2], is the most widely used DMARD for the treatment of rheumatoid arthritis (RA). However, not all patients are responsive to the drug; 30% of the patients discontinue therapy within 1 year of commencing the treatment, usually because of the lack of efficacy or undesirable adverse effects Small-molecule Janus kinase inhibitors are clinically developed for the treatment of RA.Objectives:The aim of this study is to investigate the relative efficacy and safety of tofacitinib, baricitinib, upadacitinib, and filgotinib in comparison with adalimumab in patients with active RA and having inadequate responses to MTX.Methods:We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) to examine the efficacy and safety of tofacitinib, baricitinib, upadacitinib, filgotinib, and adalimumab in RA patients having inadequate responses to MTX.Results:Four RCTs, comprising 5,451 patients, met the inclusion criteria. The baricitinib 4mg+MTX and upadacitinib 15mg+MTX group showed a significantly higher American College of Rheumatology 20% (ACR20) response rate than the adalimumab 40mg+MTX group. The ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that baricitinib 4mg+MTX had the highest probability of being the best treatment for achieving the ACR20 response rate, followed by upadacitinib 15mg+MTX, tofacitinib 5mg+MTX, filgotinib 200mg+MTX, filgotinib 100mg+MTX, adalimumab 40mg+MTX, and placebo+MTX. The upadacitinib 15mg+MTX and baricitinib 4mg+MTX groups showed significantly higher ACR50 and ACR70 response rates than adalimumab 40mg+MTX. In terms of Herpes zoster infection, the ranking probability based on the SUCRA indicated that placebo+MTX were likely to be the safest treatments, followed by filgotinib 200mg+MTX, filgotinib 100mg+MTX, adalimumab 40mg+MTX, tofacitinib 5mg+MTX, upadacitinib 15mg+MTX, and baricitinib 4mg+MTX. Regarding safety analysis, no statistically significant differences were found between the respective intervention groups.Conclusion:In RA patients with an inadequate response to MTX, baricitinib 4mg+MTX and upadacitinib 15mg+MTX showed the highest ACR response rates, suggesting a difference in efficacy among the different JAK inhibitors.References:[1]Fleischmann R, Mysler E, Hall S, Kivitz AJ, Moots RJ, Luo Z, DeMasi R, Soma K, Zhang R, Takiya LJTL (2017) Efficacy and safety of tofacitinib monotherapy, tofacitinib with methotrexate, and adalimumab with methotrexate in patients with rheumatoid arthritis (ORAL Strategy): a phase 3b/4, double-blind, head-to-head, randomised controlled trial. 390:457-468[2]Taylor PC, Keystone EC, van der Heijde D et al (2017) Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis. N Engl J Med 376:652-662[3]Fleischmann R, Pangan AL, Mysler E, Bessette L, Peterfy C, Durez P, Ostor A, Li Y, Zhou Y, Othman AA (2018) A phase 3, randomized, double-blind study comparing upadacitinib to placebo and to adalimumab, in patients with active rheumatoid arthritis with inadequate response to methotrexate. ARTHRITIS & RHEUMATOLOGY. WILEY 111 RIVER ST, HOBOKEN 07030-5774, NJ USA, pp[4]Combe B, Kivitz A, Tanaka Y, van der Heijde D, Matzkies F, Bartok B, Ye L, Guo Y, Tasset C, Sundy J (2019) LB0001 EFFICACY AND SAFETY OF FILGOTINIB FOR PATIENTS WITH RHEUMATOID ARTHRITIS WITH INADEQUATE RESPONSE TO METHOTREXATE: FINCH1 PRIMARY OUTCOME RESULTS. BMJ Publishing Group Ltd, ppDisclosure of Interests:None declared

Efficacy and Safety of CE-224,535, an Antagonist of P2X7Receptor, in Treatment of Patients with Rheumatoid Arthritis Inadequately Controlled by Methotrexate

2012 ◽  
Vol 39 (4) ◽  
pp. 720-727 ◽  
Author(s):  
THOMAS C. STOCK ◽  
BRADLEY J. BLOOM ◽  
NATHAN WEI ◽  
SALIHA ISHAQ ◽  
WON PARK ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Response Rate ◽  
Tolerability Profile ◽  
Inadequate Response ◽  
Efficacy And Safety ◽  
Acr20 Response ◽  
Link Type ◽  
Significant Difference ◽  
Acr20 Response Rate

Objective.To evaluate efficacy and safety of CE-224,535, a selective P2X7receptor antagonist, versus placebo, in patients with active rheumatoid arthritis (RA) and inadequate response to methotrexate (MTX).Methods.In our phase IIA study (ClinicalTrials.govno.NCT00628095; A6341009), patients aged ≥ 18 years with active RA were randomized to receive either CE-224,535 (500 mg bid) or placebo for 12 weeks; all patients continued a stable background dose of ≥ 7.5 mg MTX.Results.The American College of Rheumatology 20% (ACR20) response rate (primary efficacy endpoint) was not significantly different from placebo for CE-224,535 (34.0% vs 36.2%; p = 0.591) at Week 12, or at any timepoint over the 12-week treatment period. There was no significant difference at Week 12 for the ACR20 response rate following subgroup analyses by age, sex, baseline disease activity, baseline duration of disease, geographic region, or concomitant use of steroids. ACR50/ACR70 response rates and change from baseline in Disease Activity Score 28-joint C-reactive protein (DAS28-3-CRP) and Health Assessment Questionnaire-Disability Index for CE-224,535 were not significant at Week 12 versus placebo. Treatment-emergent adverse events (AE) were reported by 62.3% (CE-224,535) and 55.3% (placebo) of patients; the most common AE were nausea (11.3%, CE-224,535; 4.3%, placebo) and diarrhea (7.5%, CE-224,535; 4.3%, placebo). The proportion of patients discontinuing due to an AE was 9.4% (CE-224,535) and 6.4% (placebo); no deaths were reported. Serious AE occurred in 3.8% (CE-224,535) and 2.1% (placebo) of patients; none was considered treatment-related.Conclusion.CE-224,535 was not efficacious, compared with placebo, for the treatment of RA in patients with an inadequate response to MTX. CE-224,535 demonstrated an acceptable safety and tolerability profile.

scholarly journals Efficacy and safety of peficitinib (ASP015K) in patients with rheumatoid arthritis and an inadequate response to conventional DMARDs: a randomised, double-blind, placebo-controlled phase III trial (RAJ3)

2019 ◽  
Vol 78 (10) ◽  
pp. 1320-1332 ◽  
Author(s):  
Yoshiya Tanaka ◽  
Tsutomu Takeuchi ◽  
Sakae Tanaka ◽  
Atsushi Kawakami ◽  
Manabu Iwasaki ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Response Rates ◽  
Janus Kinase ◽  
Phase Iii ◽  
Inadequate Response ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Acr20 Response ◽  
Once Daily ◽  
Conventional Dmards

ObjectivesTo investigate the efficacy and safety of peficitinib, an oral Janus kinase inhibitor, in patients with rheumatoid arthritis (RA).MethodsIn this double-blind phase III study, patients with RA and an inadequate response to prior disease-modifying anti-rheumatic drugs (DMARDs) were randomised to peficitinib 100 mg once daily, peficitinib 150 mg once daily, placebo or open-label etanercept for 52 weeks’ treatment; placebo-treated patients were switched at week 12 to peficitinib 100 or 150 mg once daily. The primary endpoint was American College of Rheumatology (ACR)20 response at week 12/early termination (ET). Secondary endpoints (assessed throughout) included ACR20, ACR50 and ACR70 response, changes from baseline in disease activity scores (DAS)28 and ACR core parameters, adverse events (AEs) and changes in clinical or laboratory measurements.ResultsIn total, 507 patients received treatment. ACR20 response rates at week 12/ET were significantly higher in the peficitinib 100 mg (57.7%) and 150 mg (74.5%) groups versus placebo (30.7%) (p<0.001). ACR50/70 response rates were also higher for both peficitinib doses versus placebo. Improvements in ACR response were maintained until week 52. Changes from baseline in DAS28-C-reactive protein/erythrocyte sedimentation rate and the ACR core set were significantly greater for both peficitinib doses versus placebo at week 12/ET (p<0.001). AE incidence was similar across treatment arms. Incidence of serious infection and herpes zoster-related disease was higher with peficitinib versus placebo, but with no clear dose-dependent increase.ConclusionsIn patients with RA and inadequate response to DMARDs, peficitinib 100 mg once daily or 150 mg once daily was efficacious in reducing RA symptoms and was well tolerated compared with placebo.Trial registration numberNCT02308163.

scholarly journals Efficacy and safety of peficitinib (ASP015K) in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a phase III randomised, double-blind, placebo-controlled trial (RAJ4) in Japan

2019 ◽  
Vol 78 (10) ◽  
pp. 1305-1319 ◽  
Author(s):  
Tsutomu Takeuchi ◽  
Yoshiya Tanaka ◽  
Sakae Tanaka ◽  
Atsushi Kawakami ◽  
Manabu Iwasaki ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Japanese Patients ◽  
Janus Kinase ◽  
Phase Iii ◽  
Tolerability Profile ◽  
Inadequate Response ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Acr20 Response ◽  
Once Daily

ObjectiveTo evaluate the efficacy and safety of the oral Janus kinase (JAK) inhibitor peficitinib versus placebo in Japanese patients with rheumatoid arthritis (RA).MethodsIn this multicentre, double-blind, parallel-group, placebo-controlled phase III study, patients with RA and inadequate response to methotrexate (MTX) were randomised 1:1:1 to placebo, peficitinib 100 mg once daily or peficitinib 150 mg once daily with MTX for 52 weeks. Based on baseline randomisation, at week 12, non-responders receiving placebo were switched to peficitinib until the end of treatment; the remaining patients were switched to peficitinib at week 28. Primary efficacy variables were American College of Rheumatology (ACR)20 response rate at week 12/early termination (ET) and change from baseline in van der Heijde-modified total Sharp score (mTSS) at week 28/ET.Results519 patients were randomised and treated. Significantly more (p<0.001) peficitinib (58.6%, 100 mg; 64.4%, 150 mg) than placebo (21.8%) recipients achieved ACR20 response at week 12/ET. Significantly lower (p<0.001) mean changes from baseline in mTSS at week 28/ET occurred in peficitinib (1.62, 100 mg; 1.03, 150 mg) than placebo (3.37) recipients. Peficitinib was associated with haematological and biochemical parameter changes, and increased incidence of serious infections and herpes zoster-related disease. One death from suicide occurred in a patient in the placebo group after switching to peficitinib 100 mg.ConclusionsIn Japanese patients with RA and inadequate response to MTX, peficitinib demonstrated significant superiority versus placebo in reducing RA symptoms and suppressing joint destruction. Peficitinib had an acceptable safety and tolerability profile, with no new safety signals compared with other JAK inhibitors.Trial registration numberNCT02305849.

Efficacy and Safety of Subcutaneous and Intravenous Loading Dose Regimens of Secukinumab in Patients with Active Rheumatoid Arthritis: Results from a Randomized Phase II Study

2016 ◽  
Vol 43 (3) ◽  
pp. 495-503 ◽  
Author(s):  
Witold Tlustochowicz ◽  
Proton Rahman ◽  
Bruno Seriolo ◽  
Gerhard Krammer ◽  
Brian Porter ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Active Rheumatoid Arthritis ◽  
Joint Disease ◽  
Inadequate Response ◽  
Efficacy And Safety ◽  
Acr20 Response ◽  
Link Type

Objective.To evaluate the efficacy and safety of secukinumab, a fully human antiinterleukin-17A monoclonal antibody, administered with an intravenous (IV) or subcutaneous (SC) loading regimen versus placebo, in patients with active rheumatoid arthritis (RA).Methods.In this phase II, double-blind, double-dummy, 52-week study (ClinicalTrials.govNCT01359943), 221 patients with inadequate response to methotrexate were randomized (2:2:1) to secukinumab, IV loading 10 mg/kg at baseline, Weeks 2 and 4, then SC 150 mg every 4 weeks (n = 88); secukinumab SC loading 150 mg once weekly for 5 weeks, then every 4 weeks (n = 89); or a matching placebo (followed by secukinumab 150 mg every 4 weeks starting Week 16; n = 44). The primary endpoint was superior efficacy of pooled secukinumab versus placebo using American College of Rheumatology 20% response (ACR20) at Week 12.Results.The primary efficacy endpoint was not met: ACR20 response at Week 12 was 49.2% for pooled secukinumab versus 40.9% for placebo (p = 0.3559). These variables improved significantly with pooled secukinumab versus placebo at Week 12 (all p < 0.05): the 28-joint Disease Activity Score (DAS28), patient’s and physician’s global assessment of disease activity, patient’s assessment of RA pain, and high-sensitivity C-reactive protein levels. Results of continuous efficacy outcomes were similar between the IV and SC loading regimens. The most frequent adverse events were infections, with similar rates across secukinumab and placebo.Conclusion.Although the primary endpoint (ACR20) was not met, secukinumab demonstrated improved efficacy in reducing disease activity over placebo as measured by DAS28 and other secondary endpoints.

Efficacy and safety of sarilumab in combination with methotrexate in patients with active rheumatoid arthritis and inadequate effect of methotrexate monotherapy (results of phase III MOBILITY study)

2019 ◽  
Vol 57 (2) ◽  
pp. 142-148 ◽  
Author(s):  
E. L. Nasonov ◽  
M. L. Stanislav ◽  
T. A. Raskina ◽  
G. V. Kuropatkin ◽  
I. V. Shirinsky ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Joint Destruction ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Acr20 Response ◽  
Radiographic Outcomes ◽  
Primary Endpoints ◽  
Average Change ◽  
Modified Total Sharp Score ◽  
Mobility Study

Objective: to study the efficacy and safety of rheumatoid arthritis (RA) treatment with monoclonal antibodies to interleukin 6 receptors (IL6R) – sarilumab (SAR) in combination with methotrexate (MT).Subjects and methods. The study included adult patients with moderate or severe RA and inadequate effect of MT monotherapy. Patients were randomized in a 1:1:1 ratio to subgroups receiving SAR (at doses of 150 or 200 mg) or placebo (PL) every 2 weeks in combination with a weekly intake of MT for 52 weeks. The primary endpoints of the study included the achievement of ACR20 after 24 weeks, the change of HAQ-DI after 16 weeks and assessment of radiological progression of joint destruction (modified total Sharp score mTSS) after 52 weeks.Results and discussion. In general, the initial characteristics of patients were similar in all groups. A statistically significant improvement of all three primary endpoints was found in the groups of patients treated with SAR 150 and 200 mg compared to the group of PL. ACR20 response after 24 weeks was achieved in 53.6% (p<0.0005), 65.9 and 19.6% of patients respectively (p<0.0001), the average change in HAQ-DI after 16 weeks was 20.53; 20.55 and 20.29 respectively (p<0.0001); the average change in mTSS after 52 weeks was 0.49; 0.11 and 2.30, respectively (p<0.0001).Conclusion. Both doses of SAR (150 and 200 mg every 2 weeks) in combination with MT demonstrated sustained clinical efficacy in patients with RA, which was confirmed by a significant improvement in symptomatic, functional and radiographic outcomes. SAR therapy was generally well tolerated. The adverse events observed in this study were consistent with the effects of the IL6 blockade.

scholarly journals Olokizumab, a monoclonal antibody against interleukin 6, in combination with methotrexate in patients with rheumatoid arthritis inadequately controlled by methotrexate: efficacy and safety results of a randomised controlled phase III study

2021 ◽  
pp. annrheumdis-2021-219876
Author(s):  
Evgeniy Nasonov ◽  
Saeed Fatenejad ◽  
Eugen Feist ◽  
Mariana Ivanova ◽  
Elena Korneva ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Activity Index ◽  
Disease Activity Index ◽  
Phase Iii ◽  
Double Blind Study ◽  
Efficacy And Safety ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Acr20 Response

ObjectiveTo evaluate the efficacy and safety of olokizumab (OKZ) in patients with active rheumatoid arthritis despite treatment with methotrexate (MTX).MethodsIn this 24-week multicentre, placebo-controlled, double-blind study, patients were randomised 1:1:1 to receive subcutaneously administered OKZ 64 mg once every 2 weeks, OKZ 64 mg once every 4 weeks, or placebo plus MTX. The primary efficacy endpoint was the proportion of patients achieving an American College of Rheumatology 20% (ACR20) response at week 12. The secondary efficacy endpoints included percentage of subjects achieving Disease Activity Score 28-joint count based on C reactive protein <3.2, Health Assessment Questionnaire Disability Index at week 12, ACR50 response and Clinical Disease Activity Index ≤2.8 at week 24. Safety and immunogenicity were assessed throughout the study.ResultsA total of 428 patients were randomised. ACR20 responses were more frequent with OKZ every 2 weeks (63.6%) and OKZ every 4 weeks (70.4%) than placebo (25.9%) (p<0.0001 for both comparisons). There were significant differences in all secondary efficacy endpoints between OKZ-treated arms and placebo. Treatment-emergent serious adverse events (TESAEs) were reported by more patients in the OKZ groups compared with placebo. Infections were the most common TESAEs. No subjects developed neutralising antidrug antibodies.ConclusionsTreatment with OKZ was associated with significant improvement in signs, symptoms and physical function of rheumatoid arthritis without discernible differences between the two regimens. Safety was as expected for this class of agents. Low immunogenicity was observed.Trial registration numberNCT02760368.

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