Sarilumab: Review of a Second IL-6 Receptor Antagonist Indicated for the Treatment of Rheumatoid Arthritis

2018 ◽  
Vol 52 (8) ◽  
pp. 780-791 ◽  
Author(s):  
Eric G. Boyce ◽  
Edward L. Rogan ◽  
Deepti Vyas ◽  
Neel Prasad ◽  
Yvonne Mai
Keyword(s):  
Rheumatoid Arthritis ◽  
Receptor Antagonist ◽  
Data Extraction ◽  
Safety Data ◽  
Health Assessment ◽  
Response Rates ◽  
Double Blind ◽  
Biologic Dmards ◽  
Das28 Remission ◽  
Synthetic Dmards

Major Objectives: To review the efficacy, safety, and economics of sarilumab, an interleukin-6 (IL-6) receptor antagonist, in the treatment of rheumatoid arthritis (RA). Data Sources: PubMed (1966 to January 2018), Clinicaltrials.gov (January 2018), and Scopus (1970 to January 2018) were searched using sarilumab, Kevzara, REGN88, and SAR153191. Study Selection and Data Extraction: Human studies published in peer-reviewed publications in English were the primary sources for efficacy and safety. Data Synthesis: Data from randomized, double-blind, controlled, published clinical studies weeks demonstrated statistically significantly higher American College of Rheumatology (ACR) 20, ACR50, and Disease Activity Score-28 (DAS28) remission response rates and improvements in DAS28 and Health Assessment Questionnaire–Disability Index scores for sarilumab monotherapy versus adalimumab monotherapy (P < 0.05) and for sarilumab versus placebo in patients receiving methotrexate or other conventional synthetic disease-modifying antirheumatic drugs (DMARDs); P < 0.05. The ACR20 and ACR50 response rates were, respectively, 56-72% and 35-46% for sarilumab, 58% and 30% for adalimumab, and 33-34% and 15-18% for placebo. DAS28 remission rates were 20-34% for sarilumab, 7% for adalimumab, and 7-10% for placebo. Sarilumab has a higher risk for neutropenia than tocilizumab, the other IL-6 inhibitor, but a lower risk for dyslipidemia, injection site reactions, and gastrointestinal perforation. The acquisition costs of sarilumab are expected to be similar to those of most other biologic DMARDs. Conclusion: Sarilumab is an alternative to biologic DMARDs or targeted synthetic DMARDs in patients with moderate to severely active RA who have not responded adequately to prior conventional synthetic DMARDs or tumor necrosis factor-α inhibitors.

scholarly journals Exploring drug cost and disease outcome in rheumatoid arthritis patients treated with biologic and targeted synthetic DMARDs in Norway in 2010–2019 – a country with a national tender system for prescription of costly drugs

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Alen Brkic ◽  
Andreas P. Diamantopoulos ◽  
Espen Andre Haavardsholm ◽  
Bjørg Tilde Svanes Fevang ◽  
Lene Kristin Brekke ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Annual Cost ◽  
Treatment Costs ◽  
Disease Outcomes ◽  
Health Authorities ◽  
Das28 Remission ◽  
Synthetic Dmards ◽  
Data Files ◽  
The Mean ◽  
The Cost

Abstract Background In Norway, an annual tender system for the prescription of biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) has been used since 2007. This study aimed to explore annual b/tsDMARDs costs and disease outcomes in Norwegian rheumatoid arthritis (RA) patients between 2010 and 2019 under the influence of the tender system. Methods RA patients monitored in ordinary clinical practice were recruited from 10 Norwegian centers. Data files from each center for each year were collected to explore demographics, disease outcomes, and the prescribed treatment. The cost of b/tsDMARDs was calculated based on the drug price given in the annual tender process. Results The number of registered RA patients increased from 4909 in 2010 to 9335 in 2019. The percentage of patients receiving a b/tsDMARD was 39% in 2010 and 45% in 2019. The proportion of b/tsDMARDs treated patients achieving DAS28 remission increased from 42 to 67%. The estimated mean annual cost to treat a patient on b/tsDMARDs fell by 47%, from 13.1 thousand euros (EUR) in 2010 to 6.9 thousand EUR in 2019. The mean annual cost to treat b/tsDMARDs naïve patients was reduced by 75% (13.0 thousand EUR in 2010 and 3.2 thousand EUR in 2019). Conclusions In the period 2010–2019, b/tsDMARD treatment costs for Norwegian RA patients were significantly reduced, whereas DAS28 remission rates increased. Our data may indicate that the health authorities’ intention to reduce treatment costs by implementing a tender system has been successful.

scholarly journals Update on the Pathomechanism, Diagnosis, and Treatment Options for Rheumatoid Arthritis

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 880 ◽  
Author(s):  
Yen-Ju Lin ◽  
Martina Anzaghe ◽  
Stefan Schülke
Keyword(s):  
Rheumatoid Arthritis ◽  
Side Effects ◽  
Bone Erosion ◽  
Treatment Options ◽  
Joint Damage ◽  
Cartilage Destruction ◽  
Biologic Dmards ◽  
Clinical Benefits ◽  
Synthetic Dmards ◽  
Inability To Work

Rheumatoid arthritis (RA) is an autoimmune disease that involves multiple joints bilaterally. It is characterized by an inflammation of the tendon (tenosynovitis) resulting in both cartilage destruction and bone erosion. While until the 1990s RA frequently resulted in disability, inability to work, and increased mortality, newer treatment options have made RA a manageable disease. Here, great progress has been made in the development of disease-modifying anti-rheumatic drugs (DMARDs) which target inflammation and thereby prevent further joint damage. The available DMARDs are subdivided into (1) conventional synthetic DMARDs (methotrexate, hydrochloroquine, and sulfadiazine), (2) targeted synthetic DMARDs (pan-JAK- and JAK1/2-inhibitors), and (3) biologic DMARDs (tumor necrosis factor (TNF)-α inhibitors, TNF-receptor (R) inhibitors, IL-6 inhibitors, IL-6R inhibitors, B cell depleting antibodies, and inhibitors of co-stimulatory molecules). While DMARDs have repeatedly demonstrated the potential to greatly improve disease symptoms and prevent disease progression in RA patients, they are associated with considerable side-effects and high financial costs. This review summarizes our current understanding of the underlying pathomechanism, diagnosis of RA, as well as the mode of action, clinical benefits, and side-effects of the currently available DMARDs.

scholarly journals Certolizumab pegol in combination with dose-optimised methotrexate in DMARD-naïve patients with early, active rheumatoid arthritis with poor prognostic factors: 1-year results from C-EARLY, a randomised, double-blind, placebo-controlled phase III study

2016 ◽  
Vol 76 (1) ◽  
pp. 96-104 ◽  
Author(s):  
P Emery ◽  
C O Bingham ◽  
G R Burmester ◽  
V P Bykerk ◽  
D E Furst ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Prognostic Factors ◽  
Structural Damage ◽  
Certolizumab Pegol ◽  
Health Assessment ◽  
Phase Iii ◽  
Sustained Remission ◽  
Double Blind ◽  
Registration Number ◽  
Modified Total Sharp Score

ObjectivesTo assess the efficacy and safety of certolizumab pegol (CZP)+dose-optimised methotrexate (MTX) versus placebo (PBO)+dose-optimised MTX in inducing and sustaining clinical remission in DMARD-naïve patients with moderate-to-severe, active, progressive rheumatoid arthritis (RA), with poor prognostic factors over 52 weeks.MethodsDMARD-naïve patients with ≤1 year of active RA were randomised (3:1) in a double-blind manner to CZP (400 mg Weeks 0, 2, 4, then 200 mg Q2W to Week 52)+MTX or PBO+MTX (the mean optimised-MTX dose=21 and 22 mg/week, respectively). Sustained remission (sREM) and sustained low disease activity (sLDA; DAS28(ESR)<2.6 and DAS28(ESR)≤3.2, respectively, at both Weeks 40 and 52) were the primary and secondary endpoints.ResultsPatients were randomised to CZP+MTX (n=660) and PBO+MTX (n=219). At Week 52, significantly more patients assigned to CZP+MTX compared with PBO+MTX achieved sREM (28.9% vs 15.0%, p<0.001) and sLDA (43.8% vs 28.6%, p<0.001). Inhibition of radiographic progression and improvements in physical functioning were significantly greater for CZP+MTX versus PBO+MTX (van der Heijde modified total Sharp score (mTSS) mean absolute change from baseline (CFB): 0.2 vs 1.8, p<0.001, rate of mTSS non-progressors: 70.3% vs 49.7%, p<0.001; least squares (LS) mean CFB in Health Assessment Questionnaire-Disability Index (HAQ-DI): −1.00 vs −0.82, p<0.001). Incidence of adverse events (AEs) and serious AEs was similar between treatment groups. Infection was the most frequent AE, with higher incidence for CZP+MTX (71.8/100 patient-years (PY)) versus PBO+MTX (52.7/100 PY); the rate of serious infection was similar between CZP+MTX (3.3/100 PY) and PBO+MTX (3.7/100 PY).ConclusionsCZP+dose-optimised MTX treatment of DMARD-naïve early RA resulted in significantly more patients achieving sREM and sLDA, improved physical function and inhibited structural damage compared with PBO+dose-optimised MTX.Trial registration numberNCT01519791.

Toreforant, A Histamine H4 Receptor Antagonist, in Patients with Active Rheumatoid Arthritis Despite Methotrexate Therapy: Results of 2 Phase II Studies

2016 ◽  
Vol 43 (9) ◽  
pp. 1637-1642 ◽  
Author(s):  
Robin L. Thurmond ◽  
Andrew Greenspan ◽  
Waldemar Radziszewski ◽  
Xie L. Xu ◽  
Ye Miao ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Receptor Antagonist ◽  
Active Rheumatoid Arthritis ◽  
Dose Range ◽  
Joint Disease ◽  
Double Blind ◽  
Once Daily ◽  
Double Blind Placebo ◽  
Range Finding ◽  
Phase Ii Studies

Objective.To assess toreforant (selective histamine H4 receptor antagonist) in active rheumatoid arthritis (RA).Methods.In a phase IIa, double-blind, placebo-controlled test, 86 patients were randomized (2:1) to once-daily toreforant 100 mg or placebo for 12 weeks. In phase IIb, double-blind, placebo-controlled, dose-range–finding evaluations, 272 patients were randomized (1:1:1:1) to once-daily placebo or toreforant 3/10/30 mg. Primary efficacy endpoints for both studies were Week 12 changes in 28-joint Disease Activity Score–C-reactive protein (DAS28-CRP).Results.Phase IIa testing was terminated prematurely (patient fatality; secondary hemophagocytic lymphohistiocytosis). Posthoc analyses indicated toreforant 100 mg/day reduced RA signs/symptoms through Week 12. Phase IIb testing, however, showed no significant Week 12 improvement in DAS28-CRP with toreforant.Conclusion.Toreforant was not effective in phase IIb testing.

scholarly journals ASP5094, a humanized monoclonal antibody against integrin alpha-9, did not show efficacy in patients with rheumatoid arthritis refractory to methotrexate: results from a phase 2a, randomized, double-blind, placebo-controlled trial

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Tsutomu Takeuchi ◽  
Yoshiya Tanaka ◽  
Jay Erdman ◽  
Yuichiro Kaneko ◽  
Masako Saito ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Monoclonal Antibody ◽  
Biological Activity ◽  
Disease Onset ◽  
Response Rates ◽  
Janus Kinase ◽  
P Value ◽  
Inadequate Response ◽  
Primary Efficacy ◽  
Double Blind

Abstract Background Rheumatoid arthritis (RA) is a chronic, debilitating autoimmune condition characterized by joint synovial inflammation. Current treatments include methotrexate (MTX), biologic agents, and Janus kinase (JAK) inhibitors. However, these agents are not efficacious in all patients and there are concerns regarding side effects and risk of infection as these treatments target immune-related pathways. Overexpression and activation of integrin alpha-9 (α9) on fibroblast-like synoviocytes are associated with RA disease onset and exacerbation. The humanized immunoglobulin G1 monoclonal antibody ASP5094 was designed to inhibit human α9 and is currently under investigation for the treatment of RA. Methods This phase 2a, multicenter, randomized, placebo-controlled, double-blind, parallel-group study (NCT03257852) evaluated the efficacy, safety, and biological activity of intravenous ASP5094 10 mg/kg in patients with moderate to severe RA that was refractory to MTX. Patients received ASP5094 or placebo every 4 weeks for a total of three administrations. Both treatment groups used concomitant MTX. The primary efficacy endpoint was the proportion of patients who responded per American College of Rheumatology 50% improvement using C-reactive protein (ACR50-CRP) after 12 weeks of treatment. Biological activity of ASP5094 was assessed via pharmacokinetics and pharmacodynamics of known downstream effectors of α9. Safety was also assessed. Results Sixty-six patients were enrolled and randomized to placebo (n = 33) or ASP5094 (n = 33). In the primary efficacy analysis, ACR50-CRP response rates were 6.3% and 18.2% at week 12 in the ASP5094 and placebo groups, respectively; a difference of − 11.9, which was not significant (2-sided P value = 0.258). No trends in ACR50 response rates were observed in subgroups based on demographics or baseline disease characteristics, and no significant differences between placebo and ASP5094 were identified in secondary efficacy or pharmacodynamic endpoints, despite achievement of target serum concentrations of ASP5094. Most treatment-emergent adverse events were mild to moderate in severity, and ASP5094 was considered safe and well tolerated overall. Conclusion Although no notable safety signals were observed in this study, ASP5094 was not efficacious in patients with moderate to severe RA with an inadequate response to MTX. Trial registration ClinicalTrials.gov, NCT03257852. Registered on 22 Aug. 2017

scholarly journals Improved pain, physical functioning and health status in patients with rheumatoid arthritis treated with CP-690,550, an orally active Janus kinase (JAK) inhibitor: results from a randomised, double-blind, placebo-controlled trial

2009 ◽  
Vol 69 (2) ◽  
pp. 413-416 ◽  
Author(s):  
J H Coombs ◽  
B J Bloom ◽  
F C Breedveld ◽  
M P Fletcher ◽  
D Gruben ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Health Status ◽  
Short Form ◽  
Controlled Trial ◽  
Health Assessment ◽  
Janus Kinase ◽  
Inadequate Response ◽  
Double Blind ◽  
Sf 36 ◽  
Factor Α

Objectives:To determine the efficacy of CP-690,550 in improving pain, function and health status in patients with moderate to severe active rheumatoid arthritis (RA) and an inadequate response to methotrexate or a tumour necrosis factor α inhibitor.Methods:Patients were randomised equally to placebo, CP-690,550 5, 15 or 30 mg twice daily for 6 weeks, with 6 weeks’ follow-up. The patient’s assessment of arthritis pain (pain), patient’s assessment of disease activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) and Short Form-36 (SF-36) were recorded.Results:At week 6, significantly more patients in the CP-690,550 5, 15 and 30 mg twice-daily groups experienced a 50% improvement in pain compared with placebo (44%, 66%, 78% and 14%, respectively), clinically meaningful reductions in HAQ-DI (⩾0.3 units) (57%, 75%, 76% and 36%, respectively) and clinically meaningful improvements in SF-36 domains and physical and mental components.Conclusions:CP-690,550 was efficacious in improving the pain, function and health status of patients with RA, from week 1 to week 6.

scholarly journals Exploring Drug Cost and Disease Outcome in Rheumatoid Arthritis Patients Treated With Biologic and Targeted Synthetic DMARDs in Norway in 2010-2019 – a Country With a National Tender System for Prescription of Costly Drugs

2021 ◽  
Author(s):  
Alen Brkic ◽  
Andreas P Diamantopoulos ◽  
Espen Andre Haavardsholm ◽  
Bjørg Tilde Svanes Fevang ◽  
Lene Kristin Brekke ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Annual Cost ◽  
Treatment Costs ◽  
Disease Outcomes ◽  
Health Authorities ◽  
Das28 Remission ◽  
Synthetic Dmards ◽  
Data Files ◽  
The Mean ◽  
The Cost

Abstract BACKGROUND: In Norway, an annual tender system for the prescription of biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) has been used since 2007. This study aimed to explore annual b/tsDMARDs costs and disease outcomes in Norwegian rheumatoid arthritis (RA) patients between 2010 and 2019 under the influence of the tender system.METHODS: RA patients monitored in ordinary clinical practice were recruited from ten Norwegian centers. Data files from each center for each year were collected to explore demographics, disease outcomes, and the prescribed treatment. The cost of b/tsDMARDs was calculated based on the drug price given in the annual tender process.RESULTS: The number of registered RA patients increased from 4909 in 2010 to 9335 in 2019. The percentage of patients receiving a b/tsDMARD was 39.4% in 2010 and 44.5% in 2019. The proportion of b/tsDMARDs treated patients achieving DAS28 remission increased from 34.8% to 61.3%. The estimated mean annual cost to treat a patient on b/tsDMARDs fell by 47.3%, from 13,1 thousand euros (EUR) in 2010 to 6.9 thousand EUR in 2019. The mean annual cost to treat b/tsDMARDs naïve patients was reduced by 75.4% (13,0 thousand EUR in 2010 and 3.2 thousand EUR in 2019).CONCLUSIONS: In the period 2010-2019, b/tsDMARD treatment costs for Norwegian RA patients were significantly reduced, whereas DAS28 remission rates increased. Our data may indicate that the health authorities’ intention to reduce treatment costs by implementing a tender system has been successful.

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