Ignite Creation Date:
2024-05-06 @ 4:07 PM
Last Modification Date:
2024-10-26 @ 2:03 PM
Study NCT ID:
NCT04870203
Status:
RECRUITING
Last Update Posted:
2024-01-31
First Post:
2021-04-26
Brief Title:
Combination of Baricitinib and Anti-TNF in Rheumatoid Arthritis
Sponsor:
University Hospital Bordeaux
Organization:
University Hospital Bordeaux
Study Overview
Official Title:
Combination of Baricitinib and Anti-TNF vs Baricitinib in Patients With Rheumatoid Arthritis a Randomized Placebo-controlled Phase III Trial
Status:
RECRUITING
Status Verified Date:
2024-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
CRI-RA
Brief Summary:
As stated by the European League Against Rheumatism EULAR and the Societe Francaise de Rhumatologie SFR treatment of patients with rheumatoid arthritis RA should target sustained remission or at least low disease activity However despite significant advances based on various combinations of conventional synthetic disease-modifying antirheumatic drugs DMARDs and biologic DMARDs RA therapies meet treatment goals only in some patients
40 to 50 of patients with early RA treated with methotrexate MTX monotherapy as first-line therapy
20 to 30 of patients treated with a combination of MTX and biologic as second-line therapy
Less than 10 of patients treated with a combination of MTX and another targeted DMARD such as baricitinib as third-line therapy
Therefore new strategies targeted at achieving a higher percentage of remission are needed that do not require waiting for multiple failed therapies Combinations of biologics have shown synergistic improvement of symptoms in murine models of RA relative to the improvement observed with either agent alone However in RA patients only five randomised clinical trials RCTs have explored the efficacy and safety of combining tumour necrosis factor TNF inhibitor with another biologic anakinra abatacept rituximab or bimekizumab
Baricitinib is a selective reversible and competitive inhibitor of Janus kinases Jaki This treatment is efficient in a number of therapeutic scenarios in RA and showed a clinical superiority over adalimumab in one RCT RA-BEAM study in MTX inadequate responders Of note baricitinib inhibits many of the pro-inflammatory cytokines involved in the pathogenesis of RA but does not block signalling downstream of TNF Owing to the interest in combining different mechanisms of action the investigators plan to assess the efficacy and safety of combination therapy with baricitinib and a TNF inhibitor The investigators are aware that combining targeted therapies is not recommended due to a potential increase in the frequency of serious adverse events However several case series on patients treated with a combination of targeted therapies have been published suggesting a certain efficacy in patients with refractory RA The first ones focused on inflammatory bowel diseases and psoriasis but more recently combination of tofacitinib which belongs to the same Jaki family as baricitinib with various biologics has been reported in a sample of RA patients No serious adverse effects were reported over a mean of approximately 11 months of therapy The clinical improvement was mild but noticeable in these refractory RA cases
Recently data of interest from the RA-BEAM study have been reported Patients who switched from adalimumab to baricitinib showed improvements in disease control Because the switch from adalimumab to baricitinib occurred without a washout period and because adalimumab has a mean circulating half-life of approximately 14 days patients would have received several weeks of dual TNF and Jak1Jak2 inhibition in the course of the change of treatment The observation of increased efficacy with no apparent acute safety issues during the weeks when patients were exposed to both adalimumab and baricitinib is of interest and supports our strategy to combine the two treatments for patients with refractory RA
The investigators consider that there is a need for investigation into the addition of anti-TNF to baricitinib in patients suffering of refractory RA inadequate response to TNF inhibitors The investigators hypothesize that in this population based on ACR50 score this combination therapy will decrease disease activity more efficiently than a switch to another targeted DMARD such as baricitinib
40 to 50 of patients with early RA treated with methotrexate MTX monotherapy as first-line therapy
20 to 30 of patients treated with a combination of MTX and biologic as second-line therapy
Less than 10 of patients treated with a combination of MTX and another targeted DMARD such as baricitinib as third-line therapy
Therefore new strategies targeted at achieving a higher percentage of remission are needed that do not require waiting for multiple failed therapies Combinations of biologics have shown synergistic improvement of symptoms in murine models of RA relative to the improvement observed with either agent alone However in RA patients only five randomised clinical trials RCTs have explored the efficacy and safety of combining tumour necrosis factor TNF inhibitor with another biologic anakinra abatacept rituximab or bimekizumab
Baricitinib is a selective reversible and competitive inhibitor of Janus kinases Jaki This treatment is efficient in a number of therapeutic scenarios in RA and showed a clinical superiority over adalimumab in one RCT RA-BEAM study in MTX inadequate responders Of note baricitinib inhibits many of the pro-inflammatory cytokines involved in the pathogenesis of RA but does not block signalling downstream of TNF Owing to the interest in combining different mechanisms of action the investigators plan to assess the efficacy and safety of combination therapy with baricitinib and a TNF inhibitor The investigators are aware that combining targeted therapies is not recommended due to a potential increase in the frequency of serious adverse events However several case series on patients treated with a combination of targeted therapies have been published suggesting a certain efficacy in patients with refractory RA The first ones focused on inflammatory bowel diseases and psoriasis but more recently combination of tofacitinib which belongs to the same Jaki family as baricitinib with various biologics has been reported in a sample of RA patients No serious adverse effects were reported over a mean of approximately 11 months of therapy The clinical improvement was mild but noticeable in these refractory RA cases
Recently data of interest from the RA-BEAM study have been reported Patients who switched from adalimumab to baricitinib showed improvements in disease control Because the switch from adalimumab to baricitinib occurred without a washout period and because adalimumab has a mean circulating half-life of approximately 14 days patients would have received several weeks of dual TNF and Jak1Jak2 inhibition in the course of the change of treatment The observation of increased efficacy with no apparent acute safety issues during the weeks when patients were exposed to both adalimumab and baricitinib is of interest and supports our strategy to combine the two treatments for patients with refractory RA
The investigators consider that there is a need for investigation into the addition of anti-TNF to baricitinib in patients suffering of refractory RA inadequate response to TNF inhibitors The investigators hypothesize that in this population based on ACR50 score this combination therapy will decrease disease activity more efficiently than a switch to another targeted DMARD such as baricitinib
Detailed Description:
Intensive combination therapies have revolutionised the management of solid neoplasms hematologic malignancies and acquired-immune-deficiency syndrome These intensive strategies are based on the need to obtain rapid control of disease activity to afford the chance of stable full remission and avoid irreversible complications The same goal applies to management of RA Because current therapeutic strategies may fall short of these target goals and fail to improve quality of life in some patients novel approaches are needed to improve outcomes RA is a complex disease involving numerous cell types and inflammatory mediators of innate and adaptive immune systems The investigators are aware that most of combination bDMARD strategies have been associated with little or no incremental benefit in efficacy compared to single-biologic therapy However our study will target mechanisms that differ from those in previous studies Strategies that simultaneously target different pathways involved in the pathogenesis of RA may enhance treatment responses in patients with RA Of note baricitinib does not directly block signalling downstream of TNF even if an indirect effect on TNF production is likely to occur Targeting multiple inflammatory cytokines in combination may lead to more effective treatment and enhanced clinical responses in patients with RA compared to the current second-line strategies The different mechanisms of action of baricitinib and anti-TNF should ensure the efficacy of the combination No concurrent trial evaluating similar strategies is registered at ClinicalTrialgov
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None