Phase 3 Rheumatoid Arthritis Clinical Development Program for Baricitinib and Filgotinib

The phase 3 clinical development programs for BARI and filgotinib included patients with moderately to severely active RA who had inadequate responses to treatment with MTX and bDMARDs or who were MTX naïve. However, there were differences in the patient populations evaluated and study designs in these clinical development programs.1-5 Therefore, no efficacy and safety comparative conclusions can be drawn by indirectly comparing the results of these programs.

Baricitinib and Filgotinib Phase 3 Clinical Trial Designs in Treatment-Naïve Patients, Baricitinib and Filgotinib Phase 3 Active Comparator Clinical Trial Designs in Patients With Inadequate Response to Methotrexate, and Baricitinib and Filgotinib Phase 3 Clinical Trial Designs in Patients With Inadequate Response to bDMARDs provide the descriptions of the phase 3 RA clinical development programs for BARI and filgotinib.

Methotrexate-Naïve Patients

The phase 3 RA clinical development programs for both BARI and filgotinib included studies in MTX-naïve patients.2,5

In the BARI program, RA-BEGIN was conducted in patients who were DMARD naïve and it compared

BARI monotherapy
dose-titrated MTX monotherapy, and
BARI plus MTX.2

In the filgotinib program, FINCH3 was conducted in patients who were MTX naïve and it compared

filgotinib monotherapy
MTX monotherapy, and
filgotinib plus MTX.5

Thus, the BARI phase 3 RA clinical program evaluated treatment in patients who were DMARD naïve, not just MTX naïve.2,6

Baricitinib and Filgotinib Phase 3 Clinical Trial Designs in Treatment-Naïve Patients2,5
	BARI RA-BEGIN	Filgotinib FINCH3
Patient population	DMARD naïve	MTX naïve
Treatment arms	BARI 4 mg mono (n=159)	FIL 200 mg mono (n=210)
	BARI + MTX (n=215)	FIL 200 mg + MTX (n=416)
	BARI + MTX (n=215)	FIL 100 mg + MTX (n=207)
	MTX mono (n=210)	MTX mono (n=416)
Background DMARDs	None	None
Duration	52 weeks	52 weeks
Primary endpoint	ACR20 at week 24	ACR20 at week 24
Secondary endpoints	mTSS and SDAI ≤3.3	ACR50, ACR70, DAS28-CRP ≤3.2 and <2.6, mTSS, HAQ-DI, SF-36 PCS, and FACIT-Fatigue

Abbreviations: ACR20 = 20% improvement in American College of Rheumatology criteria; ACR50 = 50% improvement in American College of Rheumatology criteria; ACR70 = 70% improvement in American College of Rheumatology criteria; BARI = baricitinib; DAS28-CRP = Disease Activity Score based on C-reactive protein; DMARD = disease-modifying antirheumatic drug; FACIT = Functional Assessment of Chronic Illness Therapy; FIL = filgotinib; HAQ-DI = Health Assessment Questionnaire-Disability Index; mono = monotherapy; mTSS = modified Total Sharp Score; MTX = methotrexate; SDAI = Simplified Disease Activity Index; SF-36 PCS = Short-Form 36 Physical Component Summary.

Methotrexate Inadequate Responders

The phase 3 RA clinical development programs for both BARI and filgotinib included studies in MTX-IR patients with ADA as a treatment arm.1,3

In the BARI program, RA-BEAM was statistically powered to make both non-inferiority and superiority assessments between BARI and ADA for ACR20 and superiority assessments for DAS28-hsCRP.1

In the filgotinib program, FINCH1 was statistically powered to test non-inferiority between filgotinib and ADA for DAS28-CRP ≤3.2 and <2.6.3

Baricitinib and Filgotinib Phase 3 Active Comparator Clinical Trial Designs in Patients With Inadequate Response to Methotrexate1,3
	BARI RA-BEAM	Filgotinib FINCH1
Patient population	MTX-IR	MTX-IR
Treatment arms	BARI 4 mg (n=487)	FIL 100 mg (n=480)
	BARI 4 mg (n=487)	FIL 200 mg (n=475)
	ADA (n=330)	ADA (n=325)
	PBO (n=488)	PBO (n=475)
Background DMARDs	MTX	MTX
Duration	52 weeks	52 weeks
Primary endpoint	ACR20 at week 12	ACR20 at week 12
Secondary endpoints	HAQ-DI, DAS28-CRP ≤3.2, mTSS	ACR50, ACR70, DAS28-CRP ≤3.2 and <2.6, mTSS, HAQ-DI, SF-36 PCS, and FACIT-Fatigue

Abbreviations: ACR20 = 20% improvement in American College of Rheumatology criteria; ACR50 = 50% improvement in American College of Rheumatology criteria; ACR70 = 70% improvement in American College of Rheumatology criteria; ADA = adalimumab; BARI = baricitinib; DAS28-CRP = Disease Activity Score based on C-reactive protein; DMARD = disease-modifying antirheumatic drug; FACIT = Functional Assessment of Chronic Illness Therapy; FIL = filgotinib; HAQ-DI = Health Assessment Questionnaire-Disability Index; IR = inadequate response; mono = monotherapy; mTSS = modified Total Sharp Score; MTX = methotrexate; PBO = placebo; SF-36 PCS = Short-Form 36 Physical Component Summary.

Biologic DMARD Inadequate Responders

The phase 3 RA clinical development programs for both BARI and filgotinib included studies in bDMARD-IR patients.4,7

In the BARI RA-BEACON study, more than half of the patients had previously failed more than 1 bDMARD.7

In the filgotinib FINCH2 study, 44-51% of the patients had previously failed more than 1 bDMARD.4

Baricitinib and Filgotinib Phase 3 Clinical Trial Designs in Patients With Inadequate Response to bDMARDs4,7
	BARI RA-BEACON	Filgotinib FINCH2
Patient population	TNFi-IR	bDMARD-IR
Treatment arms	BARI 2 mg (n=174)	FIL 100 mg (n=153)
	BARI 4 mg (n=177)	FIL 200 mg (n=148)
	PBO (n=176)	PBO (n=148)
	PBO (n=176)	PBO (n=148)
Background DMARDs	csDMARDs	csDMARDs
Duration	24 weeks	24 weeks
Primary endpoint	ACR20 at week 12	ACR20 at week 12
Secondary endpoints	HAQ-DI, DAS28-CRP, and SDAI ≤3.3	HAQ-DI, DAS28-CRP ≤3.2 and <2.6, SF-36 PCS, and FACIT-Fatigue

Abbreviations: ACR20 = 20% improvement in American College of Rheumatology criteria; BARI = baricitinib; bDMARD = biologic disease-modifying antirheumatic drug; csDMARD = conventional synthetic disease-modifying antirheumatic drug; DAS28-CRP = Disease Activity Score based on C-reactive protein; DMARD = disease-modifying antirheumatic drug; FACIT = Functional Assessment of Chronic Illness Therapy; FIL = filgotinib; HAQ-DI = Health Assessment Questionnaire-Disability Index; IR = inadequate response; PBO = placebo; SDAI = Simplified Disease Activity Index; SF-36 PCS = Short-Form 36 Physical Component Summary; TNFi = tumor necrosis factor inhibitor.

References

1Taylor 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

2Fleischmann 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

3Combe B, Kivitz A, Tanaka Y, et al. LB0001 efficacy and safety of filgotinib for patients with rheumatoid arthritis with inadequate response to methotrexate: FINCH1 primary outcome results. Ann Rheum Dis. 2019;78(suppl 2):77-78. European League Against Rheumatism abstract LB0001. http://dx.doi.org/10.1136/annrheumdis-2019-eular.8676

4Genovese MC, Kalunian K, Gottenberg JE, et al. Effect of filgotinib vs placebo on clinical response in patients with moderate to severe rheumatoid arthritis refractory to disease-modifying antirheumatic drug therapy: The FINCH 2 randomized clinical trial. JAMA. 2019;322(4):315-325. http://dx.doi.org/10.1001/jama.2019.9055

5Westhovens R, Rigby W, van der Heijde D, et al. LB0003 efficacy and safety of filgotinib for patients with rheumatoid arthritis naïve to methotrexate therapy: FINCH3 primary outcome results. Ann Rheum Dis. 2019;78(suppl 2):259-261. European League Against Rheumatism abstract LB0003. http://dx.doi.org/10.1136/annrheumdis-2019-eular.8678

6Filgotinib alone and in combination with methotrexate (MTX) in adults with moderately to severely active rheumatoid arthritis who are naive to MTX therapy (FINCH 3). ClinicalTrials.gov identifier: NCT02886728. Updated October 8, 2019. Accessed September 23, 2020. https://clinicaltrials.gov/show/NCT02886728

7Genovese 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

ACR20 = 20% improvement in American College of Rheumatology criteria

ADA = adalimumab

BARI = baricitinib

bDMARD = biologic disease-modifying antirheumatic drug

bDMARD-IR = inadequate response or intolerant to biologic disease-modifying antirheumatic drug treatment

DAS28-hsCRP = Disease Activity Score based on high-sensitivity C-reactive protein

DMARD = disease-modifying antirheumatic drug

MTX = methotrexate

MTX-IR = inadequate response to methotrexate

RA = rheumatoid arthritis

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Baricitinib: Comparison of Baricitinib and Filgotinib Phase 3 Rheumatoid Arthritis Clinical Development Programs