Update on Abatacept: A Selective Costimulation Modulator for Rheumatoid Arthritis

2007 ◽  
Vol 41 (7-8) ◽  
pp. 1153-1162 ◽  
Author(s):  
Susan P Bruce ◽  
Eric G Boyce
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Events ◽  
Human Studies ◽  
Inadequate Response ◽  
Upper Respiratory Tract ◽  
Serious Adverse Events ◽  
Additional Clinical Trial ◽  
Tract Infections ◽  
Necrosis Factor

Objective: To review and update the pharmacology, pharmacokinetics, safety, precautions, efficacy, and use of abatacept for rheumatoid arthritis (RA). Data Sources: Studies and abstracts were identified through MEDLINE, International Pharmaceutical Abstracts, Cochrane databases, and Science Citation Index (1990–April 2007). Key search terms included abatacept, CTLA4–Ig, and BMS 1888667. Information available only in abstract form was retrieved from national and international rheumatology associations. Additional data were obtained from the manufacturer. Study Selection and Data Extraction: All available animal and human studies describing the pharmacology of abatacept and human studies describing the pharmacokinetics, pharmacodynamics, efficacy, safety, adverse events, and precautions of abatacept were included. Data Synthesis: Abatacept significantly improves the signs and symptoms of moderate-to-severe RA in patients who experienced an Inadequate response to methotrexate or antitumor necrosis factor-α inhibitors. By month 12, approximately 50% of patients achieved remission (defined as a disease activity score <2.6) that was maintained until at least 24 months of therapy. The most common adverse events include headache, upper respiratory tract infections, nausea, and nasopharyngitis. Rare but serious adverse events include serious infections and malignancy. Conclusions: Abatacept has documented efficacy and safety in patients with inadequate responses to methotrexate and antitumor necrosis factor agents in both short- and long-term studies. Additional clinical trial and postmarketing evidence is necessary to understand the long-term safety, efficacy, economics, and rote of abatacept in clinical practice.

Efficacy and safety of the selective co-stimulation modulator abatacept following 2 years of treatment in patients with rheumatoid arthritis and an inadequate response to anti-tumour necrosis factor therapy

2007 ◽  
Vol 67 (4) ◽  
pp. 547-554 ◽  
Author(s):  
M C Genovese ◽  
M Schiff ◽  
M Luggen ◽  
J-C Becker ◽  
R Aranda ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Events ◽  
Sleep Problems ◽  
Inadequate Response ◽  
C Reactive Protein ◽  
Double Blind ◽  
Safety And Efficacy ◽  
Reactive Protein ◽  
Sf 36

Objective:To evaluate the safety and efficacy of abatacept during 2 years of the ATTAIN (Abatacept Trial in Treatment of Anti-TNF INadequate responders) trial in patients with rheumatoid arthritis.Methods:Patients completing the 6-month, double-blind period were eligible to enter the long-term extension; patients received abatacept ∼10 mg/kg, plus disease-modifying antirheumatic drugs. Safety and efficacy (American College of Rheumatology (ACR) criteria responses, DAS28 (C-reactive protein), HAQ-DI, SF-36, Medical Outcomes Study Sleep Problems Index, fatigue VAS) were assessed through 2 years.Results:317 patients (218 from the abatacept and 99 from the placebo group) entered and 222 (70%) completed 18 months of long-term extension treatment. The incidence and type of adverse events were consistent between the double-blind and cumulative (double-blind plus long-term extension) periods. Rates of serious adverse events were 25.6 and 23.4 per 100 patient-years in the double-blind versus cumulative period. At 6 months and 2 years, using non-responder analyses, ACR responses in abatacept-treated patients were: ACR 20, 59.4% and 56.2%; ACR 50, 23.5% and 33.2%; ACR 70, 11.5% and 16.1%; HAQ-DI responses were 54.4% and 47.9%. At 6 months and 2 years, using post-hoc as-observed analyses, the percentage of patients (95% confidence interval) achieving DAS28 (C-reactive protein) low disease activity score (⩽3.2) and DAS28 (C-reactive protein)-defined remission (<2.6) increased from 18.3% (13.0, 23.5) to 32.0% (24.6, 39.4) and 11.1% (6.8, 15.3) to 20.3% (13.9, 26.6). Clinically meaningful improvements in SF-36, pain, fatigue and sleep problems were also maintained throughout the 2 years of abatacept treatment.Conclusion:No unique safety observations were reported during open-label exposure. Improvements in the signs and symptoms of rheumatoid arthritis, physical function and health-related quality of life observed after 6 months, were maintained throughout the 2 years in this population with difficult-to-treat disease.Trial registration number:NCT00124982.

scholarly journals Long-term safety, efficacy and inhibition of radiographic progression with abatacept treatment in patients with rheumatoid arthritis and an inadequate response to methotrexate: 3-year results from the AIM trial

2011 ◽  
Vol 70 (10) ◽  
pp. 1826-1830 ◽  
Author(s):  
Joel M Kremer ◽  
Anthony S Russell ◽  
Paul Emery ◽  
Carlos Abud-Mendoza ◽  
Jacek Szechinski ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Radiographic Progression ◽  
Incidence Rates ◽  
Inadequate Response ◽  
Open Label ◽  
Serious Adverse Events ◽  
Double Blind ◽  
American College Of Rheumatology ◽  
Inadequate Responders

ObjectiveTo evaluate abatacept treatment over 3 years in patients with rheumatoid arthritis (RA) refractory to methotrexate (MTX).MethodsPatients randomised to abatacept or placebo (+MTX) during the 1-year double-blind period of the Abatacept in Inadequate responders to Methotrexate (AIM) trial received open-label abatacept (+MTX) in the long-term extension (LTE). Safety was assessed for patients who received ≥1 dose of abatacept, regardless of randomisation group. Efficacy was assessed for patients randomised to abatacept who entered the LTE.Results433 and 219 patients were randomised and treated with abatacept or placebo, respectively; 378 and 161 entered the LTE. At year 3, 440/539 patients were ongoing. No unexpected safety events were observed in the LTE. By year 3, incidence rates of adverse event and serious adverse events were 249.8/100 and 15.1/100 patient-years, respectively. Incidence rates were generally stable over time. At year 3, 84.8%, 63.4% and 37.5% of patients achieved American College of Rheumatology (ACR) criteria of 20, 50 and 70, respectively, compared with 82.3%, 54.3% and 32.4% of patients at year 1. Mean changes in Genant-modified Sharp scores were reduced progressively over 3 years, with significantly greater inhibition during year 3 compared with year 2 (p=0.022 for total score).ConclusionIn MTX-inadequate responders with RA, abatacept provided consistent safety and sustained efficacy over 3 years. The data suggest an increasing inhibitory disease-modifying effect on radiographic progression.

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

Low dose long-term corticosteroid therapy in rheumatoid arthritis: An analysis of serious adverse events

1994 ◽  
Vol 96 (2) ◽  
pp. 115-123 ◽  
Author(s):  
Kenneth G. Saag ◽  
Rochelle Koehnke ◽  
Jacques R. Caldwell ◽  
Richard Brasington ◽  
Leon F. Burmeister ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Events ◽  
Corticosteroid Therapy ◽  
Low Dose ◽  
Serious Adverse Events

Tralokinumab did not demonstrate oral corticosteroid-sparing effects in severe asthma

2019 ◽  
Vol 53 (2) ◽  
pp. 1800948 ◽  
Author(s):  
William W. Busse ◽  
Guy G. Brusselle ◽  
Stephanie Korn ◽  
Piotr Kuna ◽  
Antoine Magnan ◽  
...  
Keyword(s):  
Adverse Events ◽  
Severe Asthma ◽  
Oral Corticosteroid ◽  
Inhaled Corticosteroids ◽  
Upper Respiratory Tract ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Exacerbation Rate ◽  
End Point ◽  
Tract Infections

Long-term oral corticosteroid (OCS) use in patients with severe asthma is associated with significant adverse effects.This 40-week, randomised, double-blind trial evaluated the OCS-sparing potential of tralokinumab in patients with severe, uncontrolled asthma requiring maintenance OCS treatment plus inhaled corticosteroids/long-acting β2-agonists. Overall, 140 patients were randomised to tralokinumab 300 mg or placebo (n=70 in each group) administered subcutaneously every 2 weeks. The primary end-point was percentage change from baseline in average OCS dose at week 40, while maintaining asthma control. Secondary end-points included proportion of patients with a prescribed maintenance OCS dose of ≤5 mg, those with a ≥50% reduction in prescribed maintenance OCS dose and asthma exacerbation rate. Safety was also assessed.At week 40, the percentage reduction from baseline in the final daily average OCS dose was not significantly different between tralokinumab and placebo (37.62% versus 29.85%; p=0.271). There were no significant between-treatment differences for any secondary end-point. Overall, reporting of adverse events and serious adverse events were similar for the tralokinumab and placebo groups. Although a greater proportion of tralokinumab-treated patients reported upper respiratory tract infections (35.7% versus 14.3%), there were no reported cases of pneumonia.Overall, tralokinumab did not demonstrate an OCS-sparing effect in patients with severe asthma.

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 Efficacy and safety of jakinibs in rheumatoid arthritis: A systematic review and meta-analysis

2020 ◽  
Author(s):  
Yufeng Yin ◽  
Mengru Liu ◽  
Xin Chang ◽  
Michun He ◽  
Mingjun Wang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Events ◽  
Clinical Response ◽  
Cochrane Library ◽  
Controlled Trials ◽  
Inadequate Response ◽  
Efficacy And Safety ◽  
Serious Adverse Events ◽  
Increased Risk ◽  
Serious Infections

Abstract Objectives To assess the efficacy and safety of jakinibs for the treatment of active rheumatoid arthritis (RA) in patients with an inadequate response or intolerance to conventional synthetic or biologic disease-modifying antirheumatic drugs (DMARDs). Methods A systematic search was conducted in PubMed, Embase and the Cochrane Library. Randomized placebo-controlled trials (RCTs) of jakinibs in RA patients were eligible. The effective outcome was RA improvement to reach an American College of Rheumatology 20%/50%/70% (ACR20/50/70) response rate at week 12 and 24 after treatment. The safety outcomes included treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), discontinuations due to adverse events, infections and serious infections. Results Twenty-eight randomized, double-blind, controlled trials including 14500 patients were included. Both at week 12 and 24, the pooled analysis was suggestive of an effective treatment with jakinibs, represented as the increased clinical response of ACR20, ACR50 and ACR70. The subgroup analysis based on different types of jakinibs demonstrated that only peficitinib treatment had no impact on the clinical response of ACR50 or ACR70 at week 12. Jakinibs were associated with an increased incidence of infections at week 12 and TEAEs and infections at week 24. No increase in the risk of SAEs, discontinuations due to adverse events, or serious infections was observed in comparisons between treatment with jakinibs and treatment with placebo in these patients. Conclusions Jakinibs are efficacious and well tolerated in RA patients up to a period of 24 weeks, although they are associated with an increased risk of infectious complications.

scholarly journals Rheumatoid Arthritis Patients On Persistent Moderate Disease Activity On Biologics Have Adverse 5-years Outcome Compared To Persistent Low-remission Status Yet They Represent A Heterogeneous Group: Lower-moderate Has Better Functionality And Fewer Serious Adverse Events Than Higher-moderate Subgroup

2020 ◽  
Author(s):  
Irini Genitsaridi ◽  
Irini Flouri ◽  
Dimitris Plexousakis ◽  
Konstantinos Marias ◽  
Kyriaki Boki ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Practice ◽  
Adverse Events ◽  
Disease Activity ◽  
Serious Adverse Events ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Moderate Disease ◽  
Moderate Disease Activity

Abstract Background The long-term outcome of rheumatoid arthritis (RA) patients who in clinical practice, exhibit persistent moderate disease activity (pMDA) despite treatment with biologics has not been adequately studied. Herein, we analyzed the 5-year outcome of the pMDA group and assessed for within-group heterogeneity. Methods We included longitudinally-monitored RA patients from the Hellenic Registry of Biologic Therapies with persistent (cumulative time ≥50% of a 5-year period) moderate (pMDA, 3.2<DAS28≤5.1) or remission/low (pRLDA, DAS28≤3.2) disease activity. The former was further classified into persistent lower-moderate (plMDA, DAS28<4.2) and higher-moderate (phMDA, DAS28≥4.2) subgroups. Five-year trajectories of functionality (HAQ) was the primary outcome in comparing pRLDA versus pMDA and assessing heterogeneity within the pMDA subgroups through multivariable mixed-effect regression. Results We identified 295 patients with pMDA and 90 patients with pRLDA, the former group comprising of plMDA (n=133, 45%) and phMDA (n=162, 55%). pMDA was associated with worse 5-year functionality trajectory than pRLDA (+0.27 HAQ units, CI 95% +0.22 to +0.33; p<0.0001), while the phMDA subgroup had worse 5-year functionality than plMDA (+0.26 HAQ units, CI 95% 0.18 to 0.36; p<0.0001). Importantly, higher persistent disease activity was associated with more serious adverse events (SAEs) [pRLDA: 0.2±0.48 vs pMDA: 0.5±0.96, p=0.006; plMDA: 0.32 ±0.6 vs phMDA: 0.64 ±1.16, p=0.038). Male gender (p=0.017), lower baseline DAS28 (p<0.001), HAQ improvement >0.22 (p=0.029) and lower average DAS28 during the first trimester since treatment initiation (p=0.001), independently predicted grouping into pRLDA. Conclusions In clinical practice, RA patients with pMDA while on bDMARDs have adverse long-term outcome compared to lower disease activity status, while heterogeneity exists within the pMDA group in terms of 5-year functionality and SAEs. Targeted studies to better characterize pMDA subgroups are needed, in order to assist clinicians in tailoring treatments.

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