Andersone, D

Barry, J

Bello, N

Blanco Alonso, R

Combe, B

Cseuz, R

De Bono, S

De La Torre, I

Drescher, E

Dudek, A

Dudler, J

Durand, F

Dvorak, Z

Ghizdavescu, A

Holzkaemper, T

Irto, I

Kausiene, R

Keystone, EC

Krogulec, M

Larsson, E

Otawa, S

Rubbert-Roth, A

Sanchez Burson, J

Taylor, PC

Unikiene, D

Taylor, Peter

Oxford University Research Archive

Efficacy and Safety of Baricitinib Versus Placebo and Adalimumab in Patients with Moderately to Severely Active Rheumatoid Arthritis and Inadequate Response to Methotrexate: Summary Results from the 52-Week Phase 3 RA-Beam Study  Peter C. Taylor1, Marek Krogulec2, Anna Dudek3, Jean Dudler4, Edit Drescher5, Regina Cseuz6, Rasa Kausiene7, Daina Andersone8, Dalia Unikiene9, Juan Sanchez Burson10, Ricardo Blanco Alonso11, Zdeněk Dvořák12, Andrei Ghizdavescu13, Ildiko Irto14, Esbjörn Larsson15, Natalia Bello16, Jane Barry17, Frederick Durand18, Thorsten Holzkämper19, Susan Otawa20, Stephanie de Bono17, Edward C. Keystone21, Andrea Rubbert-Roth22, Bernard Combe23, Inmaculada De La Torre16  1Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Kennedy Institute of Rheumatology, University of Oxford, Oxford, UNITED KINGDOM, 2Department of Rheumatology, Rheumatology Clinic, MAK-MED, Nadarzyn, 3Department of Rheumatology, Centrum Medyczne AMED, Warsaw, POLAND, 4Department of Rheumatology, Hôpital Cantonal, Fribourg, SWITZERLAND, 5Rheumatology, Csolnoky Ferenc Hospital, Veszprém, 6Department of Rheumatology, Revita Clinic, Budapest, HUNGARY,7Department of Rheumatology, VSI Respublikine Siauliu Ligonine, Siauliai, LITHUANIA,8Department of Rheumatology, Pauls Stradins Clinical University Hospital, Riga, LATVIA, 9Department of Rheumatology, Dr. Kildos Klinika, Kaunas, LITHUANIA, 10Division of Rheumatology, Hospital de Valme, Sevilla, SPAIN, 11Department of Rheumatology, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Cantabria, SPAIN, 12Department of Rheumatology, Arthromed, s.r.o., Pardubice, CZECH REPUBLIC, 13Rheumatology Section, Eli Lilly Romania S.R.L., Bucharest, ROMANIA, 14Autoimmune Section, Lilly Hungária, Budapest, HUNGARY, 15Rheumatology Section, Eli Lilly Sweden, Solna, SWEDEN, 16Rheumatology and Biomedicines Section, Eli Lilly (Spain), Alcobendas, SPAIN, 17Rheumatology Section, Lilly UK, Basingstoke, UNITED KINGDOM, 18Rheumatology and Biomedicines Section, Lilly France, Neuilly-sur-Seine, FRANCE, 19Medical Department, Lilly Deutschland, Bad Homburg, GERMANY, 20Rheumatology Section, Eli Lilly Canada, 21Department of Rheumatology, Rebecca MacDonald Centre, Mount Sinai Hospital, University of Toronto, Toronto, ON, CANADA, 22Department of Rheumatology, Klinik I für Innere Medizin, Uniklinik Köln, Köln, GERMANY, 23Department of Rheumatology, CHRU Montpellier, Montpellier, FRANCE Background: Baricitinib, an oral JAK1/JAK2 inhibitor, has shown promising results in patients with active rheumatoid arthritis (RA). We present efficacy and safety results from the phase 3 RA-BEAM study in patients with active RA and inadequate response (IR) to methotrexate (MTX). Methods: Patients with moderate to severe RA and MTX-IR were randomized 3:3:2 to placebo, baricitinib 4 mg QD or adalimumab 40 mg biweekly. All patients continued stable background MTX therapy. Non-responders were rescued at week 16. At week 24, patients receiving placebo switched to baricitinib 4 mg QD. The study compared baricitinib, placebo and adalimumab using multiple endpoints, including non-inferiority and superiority testing; the primary endpoint was baricitinib versus placebo ACR20 response at week 12. Results: Of 1305 randomized patients, 83%, 88% and 87% completed week 52 in the placebo, baricitinib and adalimumab groups, respectively; rescue rates were 27%, 9% and 15%, respectively. ACR20 response at week 12 was higher for baricitinib versus placebo (p≤.001; Table 1). At weeks 12 and 24, significant improvements were seen for baricitinib versus placebo in ACR20/50/70 and DAS28, CDAI and SDAI low disease activity and remission rates, many by week one. Baricitinib was superior to adalimumab in ACR20 response rates at weeks 12, 24 and 52, and in DAS28-CRP≤3.2 at weeks 12 and 52. Change in mTSS at weeks 24 and 52 was significantly lower for baricitinib versus placebo (Table). At week 24, more baricitinib patients had improved physical function and reduced fatigue and pain versus placebo and adalimumab (Table). During weeks 0–24, more treatment-emergent AEs occurred with baricitinib and adalimumab versus placebo (71%, 67%, 60%); serious AE rates were 5%, 2% and 4%, respectively. By week 52, treatment-emergent AE rates for baricitinib versus adalimumab were 79% versus 77% and serious AE rates were 8% versus 4%; serious infection rates were similar across groups; three major cardiovascular events (2 baricitinib, 1 adalimumab), three deaths (2 baricitinib, 1 adalimumab), one tuberculosis case (adalimumab), and five malignancies (2 baricitinib, 3 placebo) were reported. Conclusion: In patients with moderate to severe RA and MTX-IR receiving background MTX, addition of baricitinib was associated with significant clinical improvements versus placebo and adalimumab, with an acceptable safety profile. Disclosure statement: R.C.: Consultancies: Eli Lilly. J.S.B.: Consultancies: Eli Lilly, Pfizer, UCB, Janssen. R.B.A.: Member of speakers' bureau: AbbVie, Roche, Novartis, Janssen, Eli Lilly, Pfizer, MSD. Grants/ research support: AbbVie, Roche, MSD. A.G.: Other: Eli Lilly employee. I.I.: Other: Eli Lilly employee. E.L.: Other: Eli Lilly employee. N.B.: Other: Eli Lilly employee. J.B.: Other: Eli Lilly employee. F.D.: Other: Eli Lilly employee. T.H.: Shareholder/stock ownership: Eli Lilly. Other: Eli Lilly employee. S.O.: Shareholder/stock ownership: Eli Lilly. Other: Eli Lilly employee. S.de B.: Other: Eli Lilly employee. E.C.K.: Consultancies: Eli Lilly. Grants/research support: Eli Lilly. B.C.: Honoraria: Bristol-Myers Squibb, Eli Lilly, Merck, Pfizer, Roche-Chugai, Sanofi, UCB. I.D.L.T.: Other: Eli Lilly employee.P.C.T., M.K., A.D., J.D., E.D., R.K., D.A., D.U., Z.D., and A.R-R. have declared no conflicts of interest.    Table. RA-BEAM efficacy measures up to week 52   Week 12  Week 24  Week 52    PBO (n = 488)  Bari (n = 487)  ADA (n = 330)  PBO (n = 488)  Bari (n = 487)  ADA (n = 330)  Bari (n = 487)  ADA (n = 330)  ACR20  40  70***+  61***  37  74***+  66***  71++  62  ACR50  17  45***++  35***  19  50***  46***  56++  47  ACR70  5  19***+  13***  8  30***+  22***  37  31  DAS28-CRP ≤3.2  14  44***++  35***  19  52***  48***  56+  48  DAS28-CRP <2.6  4  24***  19***  8  35***  32***  40  39  DAS28-ESR ≤3.2  7  24***  21***  10  32***  34***  39  36  DAS28-ESR <2.6  2  11***  12***  5  18***  18***  23  22  CDAI ≤10  17  40***+  33***  20  50***  48***  57+  49  CDAI ≤2.8  2  8***  7**  4  16***  12***  22  18  SDAI ≤11  16  42***+  35***  20  51***  49***  57+  49  SDAI ≤3.3  2  8***  8***  3  16***  14***  23  18  LS mean ΔmTSSa    0.90  0.41***  0.33***  0.71***  0.60***    Week 12  Week 24  Week 52    PBO (n = 488)  Bari (n = 487)  ADA (n = 330)  PBO (n = 488)  Bari (n = 487)  ADA (n = 330)  Bari (n = 487)  ADA (n = 330)  HAQ-DI MCID ≥0.22  58  75***  71***  45  73***+  64***  68++  58  FACIT-F MCID ≥3.56  59  66*  68**  43  65***+  59***  60  54  LS mean ΔDAS28-CRPa  −1.0  −2.2***+++  −1.9***  −1.1  −2.4***+  −2.2***    LS mean Δpatient’s assessment of paina  −17  −32***++  −26***  −18  −34***++  −29***  −36+++  −30  LS mean Δpatient’s global assessment of disease activitya  −17  −31***++  −27***  −17  −33***+  −29***  −36+++  −30    Week 12  Week 24  Week 52    PBO (n = 488)  Bari (n = 487)  ADA (n = 330)  PBO (n = 488)  Bari (n = 487)  ADA (n = 330)  Bari (n = 487)  ADA (n = 330)  ACR20  40  70***+  61***  37  74***+  66***  71++  62  ACR50  17  45***++  35***  19  50***  46***  56++  47    Week 12  Week 24  Week 52    PBO (n = 488)  Bari (n = 487)  ADA (n = 330)  PBO (n = 488)  Bari (n = 487)  ADA (n = 330)  Bari (n = 487)  ADA (n = 330)  ACR70  5  19***+  13***  8  30***+  22***  37  31  DAS28-CRP ≤3.2  14  44***++  35***  19  52***  48***  56+  48  DAS28-CRP <2.6  4  24***  19***  8  35***  32***  40  39  DAS28-ESR ≤3.2  7  24***  21***  10  32***  34***  39  36  DAS28-ESR <2.6  2  11***  12***  5  18***  18***  23  22  CDAI ≤10  17  40***+  33***  20  50***  48***  57+  49  CDAI ≤2.8  2  8***  7**  4  16***  12***  22  18  SDAI ≤11  16  42***+  35***  20  51***  49***  57+  49  SDAI ≤3.3  2  8***  8***  3  16***  14***  23  18  LS mean ΔmTSSa    0.90  0.41***  0.33***  0.71***  0.60***  HAQ-DI MCID ≥0.22  58  75***  71***  45  73***+  64***  68++  58  FACIT-F MCID ≥3.56  59  66*  68**  43  65***+  59***  60  54    Week 12  Week 24  Week 52    PBO (n = 488)  Bari (n = 487)  ADA (n = 330)  PBO (n = 488)  Bari (n = 487)  ADA (n = 330)  Bari (n = 487)  ADA (n = 330)  LS mean ΔDAS28-CRPa  −1.0  −2.2***+++  −1.9***  −1.1  −2.4***+  −2.2***    LS mean Δpatient’s assessment of paina  −17  −32***++  −26***  −18  −34***++  −29***  −36+++  −30  LS mean Δpatient’s global assessment of disease activitya  −17  −31***++  −27***  −17  −33***+  −29***  −36+++  −30  PBO, placebo; Bari, baricitinib; ADA, adalimumab; mTSS, modified total Sharp score; MCID, minimal clinically important difference. Patients received stable background MTX throughout the study. Data are % patients (non-responder imputation), unless otherwise stated. A Data are least square (LS) mean change from baseline; * p≤0.05, ** p≤0.01, *** p≤0.001 vs PBO; + p≤0.05, ++ p≤0.01, +++ p≤0.001 vs ADA  

English

Efficacy and safety of baricitinib versus placebo and adalimumab in patients with moderately to severely active rheumatoid arthritis and inadequate response to methotrexate: Summary results from the 52-week phase 3 RA-beam study

Efficacy and safety of baricitinib versus placebo and adalimumab in patients with moderately to severely active rheumatoid arthritis and inadequate response to methotrexate: Summary results from the 52-week phase 3 RA-beam study

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