Baricitinib: Eficacia en artritis reumatoide de los estudios clínicos fase 3

Overview of Phase 3 Clinical Trials

Each of the 4 phase 3 studies in the clinical program evaluated a distinct treatment population of patients with moderate-to-severe RA.

• RA-BEGIN compared BARI 4 mg monotherapy, BARI 4 mg plus MTX, and MTX monotherapy in patients who had limited or no prior treatment with MTX and were naïve to other DMARDs.¹

• RA-BEAM compared BARI 4 mg vs placebo or adalimumab, with background MTX, in patients with inadequate response to MTX.² 

• RA-BUILD compared BARI 2 mg and 4 mg vs placebo, with background csDMARD therapy, in patients with inadequate response to csDMARDs.³

• RA-BEACON compared BARI 2 mg and 4 mg vs placebo, with background csDMARD therapy, in patients with an inadequate response to at least one TNF inhibitor, who may also have had an inadequate response to one or more non-TNF inhibitor biologic DMARDs.⁴

Efficacy Summary

Within the phase 3 development program, BARI demonstrated improvements across relevant domains of efficacy at pre-specified endpoints, including patient-reported outcomes and radiographic progression of joint damage, compared with placebo and established standards of care in RA such as approved oral conventional and injectable biologic DMARDs.^1-4

For details on efficacy endpoints, see

• Table 1

• Table 2

• Table 3, and

• Table 4.

Table 1. Summary of Key Efficacy Assessments at Pre-Specified Endpoints in RA-BEGIN¹

Abbreviations: ACR = American College of Rheumatology; ACR20 = ACR 20% response criteria; ACR50 = ACR 50% response criteria; ACR70 = ACR 70% response criteria; BARI = baricitinib; CDAI = Clinical Disease Activity Index; DAS28-ESR = 28-joint Disease Activity Score based on erythrocyte sedimentation rate; DAS28-hsCRP = 28-joint Disease Activity Score based on high-sensitivity C-reactive protein; HAQ-DI = Health Assessment Questionnaire-Disability Index; LSM = least squares mean; MCID = minimum clinically important difference; MONO = monotherapy; mTSS = modified Total Sharp Score; MTX = methotrexate; SDAI = Simplified Disease Activity Index.

^a Data are percentage of patients (non-responder imputation). Low Disease Activity criterion: DAS28-ESR ≤3.2, CDAI≤10, SDAI≤11. Remission criterion: DAS28-ESR <2.6, CDAI ≤2.8, SDAI ≤3.3.

^b p≤.01 vs active comparator.

^c p≤.001 vs active comparator.

^d p≤.05 vs active comparator.

Table 2. Summary of Key Efficacy Assessments at Pre-Specified Endpoints in RA-BEAM²

Abbreviations: ACR = American College of Rheumatology; ACR20 = ACR 20% response criteria; ACR50 = ACR 50% response criteria; ACR70 = ACR 70% response criteria; ADA = adalimumab; BARI = baricitinib; CDAI = Clinical Disease Activity Index; csDMARD = conventional synthetic disease modifying anti-rheumatic drug; DAS28-ESR = 28-joint Disease Activity Score based on erythrocyte sedimentation rate; DAS28-hsCRP = 28-joint Disease Activity Score based on high-sensitivity C-reactive protein; HAQ-DI = Health Assessment Questionnaire-Disability Index; LSM = least squares mean; MCID = minimum clinically important difference; mTSS = modified Total Sharp Score; MTX = methotrexate; PBO = placebo; Q2W = once every 2 weeks; SDAI = Simplified Disease Activity Index.

^a Data are percentage of patients (non-responder imputation). Low Disease Activity criterion: DAS28-ESR ≤3.2, CDAI≤10, SDAI≤11. Remission criterion: DAS28-ESR <2.6, CDAI ≤2.8, SDAI ≤3.3.

^b p≤.05 vs active comparator.

^c p≤.001 vs PBO.

^d p≤.01 vs active comparator.

^e p≤.01 vs PBO.

Table 3. Summary of Key Efficacy Assessments at Pre-Specified Endpoints in RA-BUILD³

Abbreviations: ACR = American College of Rheumatology; ACR20 = ACR 20% response criteria; ACR50 = ACR 50% response criteria; ACR70 = ACR 70% response criteria; ADA = adalimumab; BARI = baricitinib; CDAI = Clinical Disease Activity Index; csDMARD = conventional synthetic disease modifying anti-rheumatic drug; DAS28-ESR = 28-joint Disease Activity Score based on erythrocyte sedimentation rate; DAS28-hsCRP = 28-joint Disease Activity Score based on high-sensitivity C-reactive protein; HAQ-DI = Health Assessment Questionnaire-Disability Index; LSM = least squares mean; MCID = minimum clinically important difference; mTSS = modified Total Sharp Score; NA = not applicable; PBO = placebo; SDAI = Simplified Disease Activity Index.

^a Data are percentage of patients (non-responder imputation). Low Disease Activity criterion: DAS28-ESR ≤3.2, CDAI≤10, SDAI≤11. Remission criterion: DAS28-ESR <2.6, CDAI ≤2.8, SDAI ≤3.3.

^b p≤.001 vs PBO.

^c p≤.01 vs PBO.

Table 4. Summary of Key Efficacy Assessments at Pre-Specified Endpoints in RA-BEACON⁴

Abbreviations: ACR = American College of Rheumatology; ACR20 = ACR 20% response criteria; ACR50 = ACR 50% response criteria; ACR70 = ACR 70% response criteria; BARI = baricitinib; CDAI = Clinical Disease Activity Index; csDMARD = conventional synthetic disease modifying anti-rheumatic drug; DAS28-ESR = 28-joint Disease Activity Score based on erythrocyte sedimentation rate; DAS28-hsCRP = 28-joint Disease Activity Score based on high-sensitivity C-reactive protein; HAQ-DI = Health Assessment Questionnaire-Disability Index; LSM = least squares mean; MCID = minimum clinically important difference; mTSS = modified Total Sharp Score; NA = not applicable; PBO = placebo; SDAI = Simplified Disease Activity Index.

^a Data are percentage of patients (non-responder imputation). Low Disease Activity criterion: DAS28-ESR ≤3.2, CDAI≤10, SDAI≤11. Remission criterion: DAS28-ESR <2.6, CDAI ≤2.8, SDAI ≤3.3.

^b p≤.001 vs PBO.

^c p≤.01 vs PBO.

^d p≤.05 vs PBO.

Safety Summary

No clinically relevant increases in important measures of safety including event rates across treatment groups for malignancy, MACE, and serious infections were observed for the BARI 4-mg group compared to the active comparator or placebo. Clinically relevant measures of tolerability and adverse events leading to discontinuation of study treatment occurred in similar frequency in patients receiving BARI and the active comparator DMARD (MTX or adalimumab).^1-4

The proportions of patients in each study who reported a TEAE or SAE are shown in Table 5.

Table 5. Proportion of Patients Reporting a TEAE or SAE in the Phase 3 Clinical Trials^1-4

Abbreviations: BARI = baricitinib; MTX = methtrexate; SAE = serious adverse event; TEAE = treatment-emergent adverse event.

^a Data through 52 weeks.

^b Data through 24 weeks.

References

1. Fleischmann R, Schiff M, van der Heijde D, et al. Baricitinib, methotrexate, or combination in patients with rheumatoid arthritis and no or limited prior disease-modifying antirheumatic drug treatment. Arthritis Rheumatol. 2017;69(3):506-517. http://dx.doi.org/10.1002/art.39953

2. Taylor PC, Keystone EC, van der Heijde D, et al. Baricitinib versus placebo or adalimumab in rheumatoid arthritis. N Engl J Med. 2017;376(7):652-662. http://dx.doi.org/10.1056/NEJMoa1608345

3. Dougados M, van der Heijde D, Chen YC, et al. Baricitinib in patients with inadequate response or intolerance to conventional synthetic DMARDs: results from the RA-BUILD study [published correction appears in Ann Rheum Dis. 2017;76(9):1634. http://dx.doi.org/10.1136/annrheumdis-2016-210094corr1 ]. Ann Rheum Dis. 2017;76(1):88-95. http://dx.doi.org/10.1136/annrheumdis-2016-210094

4. Genovese MC, Kremer J, Zamani O, et al. Baricitinib in patients with refractory rheumatoid arthritis. N Engl J Med. 2016;374(13):1243-1252. http://dx.doi.org/10.1056/NEJMoa1507247

Glossary

BARI = baricitinib

csDMARD = conventional synthetic disease-modifying antirheumatic drug

DMARD = disease-modifying antirheumatic drug

MACE = major adverse cardiovascular event

MTX = methotrexate

RA = rheumatoid arthritis

SAE = serious adverse event

TEAE = treatment-emergent adverse event

TNF = tumor necrosis factor