The Year in Review RA and

SLE

Ronald van Vollenhoven

RA NEW DRUGS

Original Article

Baricitinib in Patients with Refractory Rheumatoid Arthritis

Mark C Genovese MD Joel Kremer MD Omid Zamani MD Charles Ludivico MD Marek Krogulec MD Li Xie MS Scott D Beattie PhD Alisa E

Koch MD Tracy E Cardillo MS Terence P Rooney MD William L Macias MD PhD Stephanie de Bono MD PhD Douglas E Schlichting MS

and Josef S Smolen MD

N Engl J MedVolume 374(13)1243-1252

March 31 2016

Study Overview

bull Phase 3 study in patients with an inadequate response to biologic disease-modifying antirheumatic drugs

bull Baricitinib JAK12 inhibitor

bull Double-blinded randomized controlled trial

bull Baricitinib 2 mg or 4 mg qD versus placebo

bull 24-week trial primary outcome at 12 weeks

Numbers of Patients Who Were Randomly Assigned to a Study Group and Who Completed the Study at Week 24

Genovese MC et al N Engl J Med 20163741243-1252

Characteristics of the Study Participants and Disease Activity at Baseline

Genovese MC et al N Engl J Med 20163741243-1252

Primary and Secondary Efficacy End Points

Genovese MC et al N Engl J Med 20163741243-1252

Safety and Laboratory Data Week 0 to Week 12 and Week 0 to Week 24

Genovese MC et al N Engl J Med 20163741243-1252

Conclusions

bull In patients with rheumatoid arthritis and an inadequate response to biologic DMARDs baricitinib at a daily dose of 4 mg was associated with clinical improvement at 12 weeks

bull Infections were more frequent with baricitinib than with placebo

Original Article

Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis

Peter C Taylor MD PhD Edward C Keystone MD Deacutesireacutee van der Heijde MD PhD Michael E Weinblatt MD Liliana del Carmen Morales MD

Jaime Reyes Gonzaga MD Sergey Yakushin MD Taeko Ishii MD Kahaku Emoto MD Scott Beattie PhD Vipin Arora PhD Carol Gaich PharmD

Terence Rooney MD Douglas Schlichting RN PhD William L Macias MD PhD Stephanie de Bono MD PhD and Yoshiya Tanaka MD PhD

N Engl J MedVolume 376(7)652-662

February 16 2017

Study Overview

bull Phase 3 randomized trial

bull Patients with rheumatoid arthritis on background MTX

bull Baricitinib versus adalimumab versus placebo

Characteristics of the Study Patients and Disease Activity at Baseline

Taylor PC et al N Engl J Med 2017376652-662

Primary and Secondary Efficacy End Points

Taylor PC et al N Engl J Med 2017376652-662

Inhibition of Radiographic Progression of Structural Joint Damage at Week 24

Taylor PC et al N Engl J Med 2017376652-662

Safety and Laboratory Data Week 0 to Week 24 and Week 0 to Week 52

Taylor PC et al N Engl J Med 2017376652-662

Conclusions

bull In patients with rheumatoid arthritis who had had an inadequate response to methotrexate baricitinib was associated with significant clinical improvements as compared with placebo

bull Clinical and radiological outcomes were statistically significantly better with baricitinib than with adalimumab

Efficacy and safety of sirukumab in patients with active rheumatoid arthritis refractory

to anti-TNF therapy (SIRROUND-T) a randomised double-blind placebo-controlled

parallel-group multinational phase 3 study

Daniel Aletaha MD Clifton O Bingham MD Prof Yoshiya Tanaka MD Prasheen Agarwal PhD Regina Kurrasch MD Prof Paul P Tak

MD Sharon Popik MD

The Lancet

Volume 389 Issue 10075 Pages 1206-1217 (March 2017) DOI 101016S0140-6736(17)30401-4

Copyright copy 2017 Elsevier Ltd Terms and Conditions

RA NEW DRUGS

Original Article

Baricitinib in Patients with Refractory Rheumatoid Arthritis

Mark C Genovese MD Joel Kremer MD Omid Zamani MD Charles Ludivico MD Marek Krogulec MD Li Xie MS Scott D Beattie PhD Alisa E

Koch MD Tracy E Cardillo MS Terence P Rooney MD William L Macias MD PhD Stephanie de Bono MD PhD Douglas E Schlichting MS

and Josef S Smolen MD

N Engl J MedVolume 374(13)1243-1252

March 31 2016

Study Overview

bull Phase 3 study in patients with an inadequate response to biologic disease-modifying antirheumatic drugs

bull Baricitinib JAK12 inhibitor

bull Double-blinded randomized controlled trial

bull Baricitinib 2 mg or 4 mg qD versus placebo

bull 24-week trial primary outcome at 12 weeks

Numbers of Patients Who Were Randomly Assigned to a Study Group and Who Completed the Study at Week 24

Genovese MC et al N Engl J Med 20163741243-1252

Characteristics of the Study Participants and Disease Activity at Baseline

Genovese MC et al N Engl J Med 20163741243-1252

Primary and Secondary Efficacy End Points

Genovese MC et al N Engl J Med 20163741243-1252

Safety and Laboratory Data Week 0 to Week 12 and Week 0 to Week 24

Genovese MC et al N Engl J Med 20163741243-1252

Conclusions

bull In patients with rheumatoid arthritis and an inadequate response to biologic DMARDs baricitinib at a daily dose of 4 mg was associated with clinical improvement at 12 weeks

bull Infections were more frequent with baricitinib than with placebo

Original Article

Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis

Peter C Taylor MD PhD Edward C Keystone MD Deacutesireacutee van der Heijde MD PhD Michael E Weinblatt MD Liliana del Carmen Morales MD

Jaime Reyes Gonzaga MD Sergey Yakushin MD Taeko Ishii MD Kahaku Emoto MD Scott Beattie PhD Vipin Arora PhD Carol Gaich PharmD

Terence Rooney MD Douglas Schlichting RN PhD William L Macias MD PhD Stephanie de Bono MD PhD and Yoshiya Tanaka MD PhD

N Engl J MedVolume 376(7)652-662

February 16 2017

Study Overview

bull Phase 3 randomized trial

bull Patients with rheumatoid arthritis on background MTX

bull Baricitinib versus adalimumab versus placebo

Characteristics of the Study Patients and Disease Activity at Baseline

Taylor PC et al N Engl J Med 2017376652-662

Primary and Secondary Efficacy End Points

Taylor PC et al N Engl J Med 2017376652-662

Inhibition of Radiographic Progression of Structural Joint Damage at Week 24

Taylor PC et al N Engl J Med 2017376652-662

Safety and Laboratory Data Week 0 to Week 24 and Week 0 to Week 52

Taylor PC et al N Engl J Med 2017376652-662

Conclusions

bull In patients with rheumatoid arthritis who had had an inadequate response to methotrexate baricitinib was associated with significant clinical improvements as compared with placebo

bull Clinical and radiological outcomes were statistically significantly better with baricitinib than with adalimumab

Efficacy and safety of sirukumab in patients with active rheumatoid arthritis refractory

to anti-TNF therapy (SIRROUND-T) a randomised double-blind placebo-controlled

parallel-group multinational phase 3 study

Daniel Aletaha MD Clifton O Bingham MD Prof Yoshiya Tanaka MD Prasheen Agarwal PhD Regina Kurrasch MD Prof Paul P Tak

MD Sharon Popik MD

The Lancet

Volume 389 Issue 10075 Pages 1206-1217 (March 2017) DOI 101016S0140-6736(17)30401-4

Copyright copy 2017 Elsevier Ltd Terms and Conditions

Original Article

Baricitinib in Patients with Refractory Rheumatoid Arthritis

Mark C Genovese MD Joel Kremer MD Omid Zamani MD Charles Ludivico MD Marek Krogulec MD Li Xie MS Scott D Beattie PhD Alisa E

Koch MD Tracy E Cardillo MS Terence P Rooney MD William L Macias MD PhD Stephanie de Bono MD PhD Douglas E Schlichting MS

and Josef S Smolen MD

N Engl J MedVolume 374(13)1243-1252

March 31 2016

Study Overview

bull Phase 3 study in patients with an inadequate response to biologic disease-modifying antirheumatic drugs

bull Baricitinib JAK12 inhibitor

bull Double-blinded randomized controlled trial

bull Baricitinib 2 mg or 4 mg qD versus placebo

bull 24-week trial primary outcome at 12 weeks

Numbers of Patients Who Were Randomly Assigned to a Study Group and Who Completed the Study at Week 24

Genovese MC et al N Engl J Med 20163741243-1252

Characteristics of the Study Participants and Disease Activity at Baseline

Genovese MC et al N Engl J Med 20163741243-1252

Primary and Secondary Efficacy End Points

Genovese MC et al N Engl J Med 20163741243-1252

Safety and Laboratory Data Week 0 to Week 12 and Week 0 to Week 24

Genovese MC et al N Engl J Med 20163741243-1252

Conclusions

bull In patients with rheumatoid arthritis and an inadequate response to biologic DMARDs baricitinib at a daily dose of 4 mg was associated with clinical improvement at 12 weeks

bull Infections were more frequent with baricitinib than with placebo

Original Article

Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis

Peter C Taylor MD PhD Edward C Keystone MD Deacutesireacutee van der Heijde MD PhD Michael E Weinblatt MD Liliana del Carmen Morales MD

Jaime Reyes Gonzaga MD Sergey Yakushin MD Taeko Ishii MD Kahaku Emoto MD Scott Beattie PhD Vipin Arora PhD Carol Gaich PharmD

Terence Rooney MD Douglas Schlichting RN PhD William L Macias MD PhD Stephanie de Bono MD PhD and Yoshiya Tanaka MD PhD

N Engl J MedVolume 376(7)652-662

February 16 2017

Study Overview

bull Phase 3 randomized trial

bull Patients with rheumatoid arthritis on background MTX

bull Baricitinib versus adalimumab versus placebo

Characteristics of the Study Patients and Disease Activity at Baseline

Taylor PC et al N Engl J Med 2017376652-662

Primary and Secondary Efficacy End Points

Taylor PC et al N Engl J Med 2017376652-662

Inhibition of Radiographic Progression of Structural Joint Damage at Week 24

Taylor PC et al N Engl J Med 2017376652-662

Safety and Laboratory Data Week 0 to Week 24 and Week 0 to Week 52

Taylor PC et al N Engl J Med 2017376652-662

Conclusions

bull In patients with rheumatoid arthritis who had had an inadequate response to methotrexate baricitinib was associated with significant clinical improvements as compared with placebo

bull Clinical and radiological outcomes were statistically significantly better with baricitinib than with adalimumab

Efficacy and safety of sirukumab in patients with active rheumatoid arthritis refractory

to anti-TNF therapy (SIRROUND-T) a randomised double-blind placebo-controlled

parallel-group multinational phase 3 study

Daniel Aletaha MD Clifton O Bingham MD Prof Yoshiya Tanaka MD Prasheen Agarwal PhD Regina Kurrasch MD Prof Paul P Tak

MD Sharon Popik MD

The Lancet

Volume 389 Issue 10075 Pages 1206-1217 (March 2017) DOI 101016S0140-6736(17)30401-4

Copyright copy 2017 Elsevier Ltd Terms and Conditions

Study Overview

bull Phase 3 study in patients with an inadequate response to biologic disease-modifying antirheumatic drugs

bull Baricitinib JAK12 inhibitor

bull Double-blinded randomized controlled trial

bull Baricitinib 2 mg or 4 mg qD versus placebo

bull 24-week trial primary outcome at 12 weeks

Numbers of Patients Who Were Randomly Assigned to a Study Group and Who Completed the Study at Week 24

Genovese MC et al N Engl J Med 20163741243-1252

Characteristics of the Study Participants and Disease Activity at Baseline

Genovese MC et al N Engl J Med 20163741243-1252

Primary and Secondary Efficacy End Points

Genovese MC et al N Engl J Med 20163741243-1252

Safety and Laboratory Data Week 0 to Week 12 and Week 0 to Week 24

Genovese MC et al N Engl J Med 20163741243-1252

Conclusions

bull In patients with rheumatoid arthritis and an inadequate response to biologic DMARDs baricitinib at a daily dose of 4 mg was associated with clinical improvement at 12 weeks

bull Infections were more frequent with baricitinib than with placebo

Original Article

Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis

Peter C Taylor MD PhD Edward C Keystone MD Deacutesireacutee van der Heijde MD PhD Michael E Weinblatt MD Liliana del Carmen Morales MD

Jaime Reyes Gonzaga MD Sergey Yakushin MD Taeko Ishii MD Kahaku Emoto MD Scott Beattie PhD Vipin Arora PhD Carol Gaich PharmD

Terence Rooney MD Douglas Schlichting RN PhD William L Macias MD PhD Stephanie de Bono MD PhD and Yoshiya Tanaka MD PhD

N Engl J MedVolume 376(7)652-662

February 16 2017

Study Overview

bull Phase 3 randomized trial

bull Patients with rheumatoid arthritis on background MTX

bull Baricitinib versus adalimumab versus placebo

Characteristics of the Study Patients and Disease Activity at Baseline

Taylor PC et al N Engl J Med 2017376652-662

Primary and Secondary Efficacy End Points

Taylor PC et al N Engl J Med 2017376652-662

Inhibition of Radiographic Progression of Structural Joint Damage at Week 24

Taylor PC et al N Engl J Med 2017376652-662

Safety and Laboratory Data Week 0 to Week 24 and Week 0 to Week 52

Taylor PC et al N Engl J Med 2017376652-662

Conclusions

bull In patients with rheumatoid arthritis who had had an inadequate response to methotrexate baricitinib was associated with significant clinical improvements as compared with placebo

bull Clinical and radiological outcomes were statistically significantly better with baricitinib than with adalimumab

Efficacy and safety of sirukumab in patients with active rheumatoid arthritis refractory

to anti-TNF therapy (SIRROUND-T) a randomised double-blind placebo-controlled

parallel-group multinational phase 3 study

Daniel Aletaha MD Clifton O Bingham MD Prof Yoshiya Tanaka MD Prasheen Agarwal PhD Regina Kurrasch MD Prof Paul P Tak

MD Sharon Popik MD

The Lancet

Volume 389 Issue 10075 Pages 1206-1217 (March 2017) DOI 101016S0140-6736(17)30401-4

Copyright copy 2017 Elsevier Ltd Terms and Conditions

Numbers of Patients Who Were Randomly Assigned to a Study Group and Who Completed the Study at Week 24

Genovese MC et al N Engl J Med 20163741243-1252

Characteristics of the Study Participants and Disease Activity at Baseline

Genovese MC et al N Engl J Med 20163741243-1252

Primary and Secondary Efficacy End Points

Genovese MC et al N Engl J Med 20163741243-1252

Safety and Laboratory Data Week 0 to Week 12 and Week 0 to Week 24

Genovese MC et al N Engl J Med 20163741243-1252

Conclusions

bull In patients with rheumatoid arthritis and an inadequate response to biologic DMARDs baricitinib at a daily dose of 4 mg was associated with clinical improvement at 12 weeks

bull Infections were more frequent with baricitinib than with placebo

Original Article

Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis

Peter C Taylor MD PhD Edward C Keystone MD Deacutesireacutee van der Heijde MD PhD Michael E Weinblatt MD Liliana del Carmen Morales MD

Jaime Reyes Gonzaga MD Sergey Yakushin MD Taeko Ishii MD Kahaku Emoto MD Scott Beattie PhD Vipin Arora PhD Carol Gaich PharmD

Terence Rooney MD Douglas Schlichting RN PhD William L Macias MD PhD Stephanie de Bono MD PhD and Yoshiya Tanaka MD PhD

N Engl J MedVolume 376(7)652-662

February 16 2017

Study Overview

bull Phase 3 randomized trial

bull Patients with rheumatoid arthritis on background MTX

bull Baricitinib versus adalimumab versus placebo

Characteristics of the Study Patients and Disease Activity at Baseline

Taylor PC et al N Engl J Med 2017376652-662

Primary and Secondary Efficacy End Points

Taylor PC et al N Engl J Med 2017376652-662

Inhibition of Radiographic Progression of Structural Joint Damage at Week 24

Taylor PC et al N Engl J Med 2017376652-662

Safety and Laboratory Data Week 0 to Week 24 and Week 0 to Week 52

Taylor PC et al N Engl J Med 2017376652-662

Conclusions

bull In patients with rheumatoid arthritis who had had an inadequate response to methotrexate baricitinib was associated with significant clinical improvements as compared with placebo

bull Clinical and radiological outcomes were statistically significantly better with baricitinib than with adalimumab

Efficacy and safety of sirukumab in patients with active rheumatoid arthritis refractory

to anti-TNF therapy (SIRROUND-T) a randomised double-blind placebo-controlled

parallel-group multinational phase 3 study

Daniel Aletaha MD Clifton O Bingham MD Prof Yoshiya Tanaka MD Prasheen Agarwal PhD Regina Kurrasch MD Prof Paul P Tak

MD Sharon Popik MD

The Lancet

Volume 389 Issue 10075 Pages 1206-1217 (March 2017) DOI 101016S0140-6736(17)30401-4

Copyright copy 2017 Elsevier Ltd Terms and Conditions

Characteristics of the Study Participants and Disease Activity at Baseline

Genovese MC et al N Engl J Med 20163741243-1252

Primary and Secondary Efficacy End Points

Genovese MC et al N Engl J Med 20163741243-1252

Safety and Laboratory Data Week 0 to Week 12 and Week 0 to Week 24

Genovese MC et al N Engl J Med 20163741243-1252

Conclusions

bull In patients with rheumatoid arthritis and an inadequate response to biologic DMARDs baricitinib at a daily dose of 4 mg was associated with clinical improvement at 12 weeks

bull Infections were more frequent with baricitinib than with placebo

Original Article

Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis

Peter C Taylor MD PhD Edward C Keystone MD Deacutesireacutee van der Heijde MD PhD Michael E Weinblatt MD Liliana del Carmen Morales MD

Jaime Reyes Gonzaga MD Sergey Yakushin MD Taeko Ishii MD Kahaku Emoto MD Scott Beattie PhD Vipin Arora PhD Carol Gaich PharmD

Terence Rooney MD Douglas Schlichting RN PhD William L Macias MD PhD Stephanie de Bono MD PhD and Yoshiya Tanaka MD PhD

N Engl J MedVolume 376(7)652-662

February 16 2017

Study Overview

bull Phase 3 randomized trial

bull Patients with rheumatoid arthritis on background MTX

bull Baricitinib versus adalimumab versus placebo

Characteristics of the Study Patients and Disease Activity at Baseline

Taylor PC et al N Engl J Med 2017376652-662

Primary and Secondary Efficacy End Points

Taylor PC et al N Engl J Med 2017376652-662

Inhibition of Radiographic Progression of Structural Joint Damage at Week 24

Taylor PC et al N Engl J Med 2017376652-662

Safety and Laboratory Data Week 0 to Week 24 and Week 0 to Week 52

Taylor PC et al N Engl J Med 2017376652-662

Conclusions

bull In patients with rheumatoid arthritis who had had an inadequate response to methotrexate baricitinib was associated with significant clinical improvements as compared with placebo

bull Clinical and radiological outcomes were statistically significantly better with baricitinib than with adalimumab

Efficacy and safety of sirukumab in patients with active rheumatoid arthritis refractory

to anti-TNF therapy (SIRROUND-T) a randomised double-blind placebo-controlled

parallel-group multinational phase 3 study

Daniel Aletaha MD Clifton O Bingham MD Prof Yoshiya Tanaka MD Prasheen Agarwal PhD Regina Kurrasch MD Prof Paul P Tak

MD Sharon Popik MD

The Lancet

Volume 389 Issue 10075 Pages 1206-1217 (March 2017) DOI 101016S0140-6736(17)30401-4

Copyright copy 2017 Elsevier Ltd Terms and Conditions

Primary and Secondary Efficacy End Points

Genovese MC et al N Engl J Med 20163741243-1252

Safety and Laboratory Data Week 0 to Week 12 and Week 0 to Week 24

Genovese MC et al N Engl J Med 20163741243-1252

Conclusions

bull In patients with rheumatoid arthritis and an inadequate response to biologic DMARDs baricitinib at a daily dose of 4 mg was associated with clinical improvement at 12 weeks

bull Infections were more frequent with baricitinib than with placebo

Original Article

Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis

Peter C Taylor MD PhD Edward C Keystone MD Deacutesireacutee van der Heijde MD PhD Michael E Weinblatt MD Liliana del Carmen Morales MD

Jaime Reyes Gonzaga MD Sergey Yakushin MD Taeko Ishii MD Kahaku Emoto MD Scott Beattie PhD Vipin Arora PhD Carol Gaich PharmD

Terence Rooney MD Douglas Schlichting RN PhD William L Macias MD PhD Stephanie de Bono MD PhD and Yoshiya Tanaka MD PhD

N Engl J MedVolume 376(7)652-662

February 16 2017

Study Overview

bull Phase 3 randomized trial

bull Patients with rheumatoid arthritis on background MTX

bull Baricitinib versus adalimumab versus placebo

Characteristics of the Study Patients and Disease Activity at Baseline

Taylor PC et al N Engl J Med 2017376652-662

Primary and Secondary Efficacy End Points

Taylor PC et al N Engl J Med 2017376652-662

Inhibition of Radiographic Progression of Structural Joint Damage at Week 24

Taylor PC et al N Engl J Med 2017376652-662

Safety and Laboratory Data Week 0 to Week 24 and Week 0 to Week 52

Taylor PC et al N Engl J Med 2017376652-662

Conclusions

bull In patients with rheumatoid arthritis who had had an inadequate response to methotrexate baricitinib was associated with significant clinical improvements as compared with placebo

bull Clinical and radiological outcomes were statistically significantly better with baricitinib than with adalimumab

Efficacy and safety of sirukumab in patients with active rheumatoid arthritis refractory

to anti-TNF therapy (SIRROUND-T) a randomised double-blind placebo-controlled

parallel-group multinational phase 3 study

Daniel Aletaha MD Clifton O Bingham MD Prof Yoshiya Tanaka MD Prasheen Agarwal PhD Regina Kurrasch MD Prof Paul P Tak

MD Sharon Popik MD

The Lancet

Volume 389 Issue 10075 Pages 1206-1217 (March 2017) DOI 101016S0140-6736(17)30401-4

Copyright copy 2017 Elsevier Ltd Terms and Conditions

Safety and Laboratory Data Week 0 to Week 12 and Week 0 to Week 24

Genovese MC et al N Engl J Med 20163741243-1252

Conclusions

bull In patients with rheumatoid arthritis and an inadequate response to biologic DMARDs baricitinib at a daily dose of 4 mg was associated with clinical improvement at 12 weeks

bull Infections were more frequent with baricitinib than with placebo

Original Article

Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis

Peter C Taylor MD PhD Edward C Keystone MD Deacutesireacutee van der Heijde MD PhD Michael E Weinblatt MD Liliana del Carmen Morales MD

Jaime Reyes Gonzaga MD Sergey Yakushin MD Taeko Ishii MD Kahaku Emoto MD Scott Beattie PhD Vipin Arora PhD Carol Gaich PharmD

Terence Rooney MD Douglas Schlichting RN PhD William L Macias MD PhD Stephanie de Bono MD PhD and Yoshiya Tanaka MD PhD

N Engl J MedVolume 376(7)652-662

February 16 2017

Study Overview

bull Phase 3 randomized trial

bull Patients with rheumatoid arthritis on background MTX

bull Baricitinib versus adalimumab versus placebo

Characteristics of the Study Patients and Disease Activity at Baseline

Taylor PC et al N Engl J Med 2017376652-662

Primary and Secondary Efficacy End Points

Taylor PC et al N Engl J Med 2017376652-662

Inhibition of Radiographic Progression of Structural Joint Damage at Week 24

Taylor PC et al N Engl J Med 2017376652-662

Safety and Laboratory Data Week 0 to Week 24 and Week 0 to Week 52

Taylor PC et al N Engl J Med 2017376652-662

Conclusions

bull In patients with rheumatoid arthritis who had had an inadequate response to methotrexate baricitinib was associated with significant clinical improvements as compared with placebo

bull Clinical and radiological outcomes were statistically significantly better with baricitinib than with adalimumab

Efficacy and safety of sirukumab in patients with active rheumatoid arthritis refractory

to anti-TNF therapy (SIRROUND-T) a randomised double-blind placebo-controlled

parallel-group multinational phase 3 study

Daniel Aletaha MD Clifton O Bingham MD Prof Yoshiya Tanaka MD Prasheen Agarwal PhD Regina Kurrasch MD Prof Paul P Tak

MD Sharon Popik MD

The Lancet

Volume 389 Issue 10075 Pages 1206-1217 (March 2017) DOI 101016S0140-6736(17)30401-4

Copyright copy 2017 Elsevier Ltd Terms and Conditions

Conclusions

bull In patients with rheumatoid arthritis and an inadequate response to biologic DMARDs baricitinib at a daily dose of 4 mg was associated with clinical improvement at 12 weeks

bull Infections were more frequent with baricitinib than with placebo

Original Article

Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis

Peter C Taylor MD PhD Edward C Keystone MD Deacutesireacutee van der Heijde MD PhD Michael E Weinblatt MD Liliana del Carmen Morales MD

Jaime Reyes Gonzaga MD Sergey Yakushin MD Taeko Ishii MD Kahaku Emoto MD Scott Beattie PhD Vipin Arora PhD Carol Gaich PharmD

Terence Rooney MD Douglas Schlichting RN PhD William L Macias MD PhD Stephanie de Bono MD PhD and Yoshiya Tanaka MD PhD

N Engl J MedVolume 376(7)652-662

February 16 2017

Study Overview

bull Phase 3 randomized trial

bull Patients with rheumatoid arthritis on background MTX

bull Baricitinib versus adalimumab versus placebo

Characteristics of the Study Patients and Disease Activity at Baseline

Taylor PC et al N Engl J Med 2017376652-662

Primary and Secondary Efficacy End Points

Taylor PC et al N Engl J Med 2017376652-662

Inhibition of Radiographic Progression of Structural Joint Damage at Week 24

Taylor PC et al N Engl J Med 2017376652-662

Safety and Laboratory Data Week 0 to Week 24 and Week 0 to Week 52

Taylor PC et al N Engl J Med 2017376652-662

Conclusions

bull In patients with rheumatoid arthritis who had had an inadequate response to methotrexate baricitinib was associated with significant clinical improvements as compared with placebo

bull Clinical and radiological outcomes were statistically significantly better with baricitinib than with adalimumab

Efficacy and safety of sirukumab in patients with active rheumatoid arthritis refractory

to anti-TNF therapy (SIRROUND-T) a randomised double-blind placebo-controlled

parallel-group multinational phase 3 study

Daniel Aletaha MD Clifton O Bingham MD Prof Yoshiya Tanaka MD Prasheen Agarwal PhD Regina Kurrasch MD Prof Paul P Tak

MD Sharon Popik MD

The Lancet

Volume 389 Issue 10075 Pages 1206-1217 (March 2017) DOI 101016S0140-6736(17)30401-4

Copyright copy 2017 Elsevier Ltd Terms and Conditions

Original Article

Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis

Peter C Taylor MD PhD Edward C Keystone MD Deacutesireacutee van der Heijde MD PhD Michael E Weinblatt MD Liliana del Carmen Morales MD

Jaime Reyes Gonzaga MD Sergey Yakushin MD Taeko Ishii MD Kahaku Emoto MD Scott Beattie PhD Vipin Arora PhD Carol Gaich PharmD

Terence Rooney MD Douglas Schlichting RN PhD William L Macias MD PhD Stephanie de Bono MD PhD and Yoshiya Tanaka MD PhD

N Engl J MedVolume 376(7)652-662

February 16 2017

Study Overview

bull Phase 3 randomized trial

bull Patients with rheumatoid arthritis on background MTX

bull Baricitinib versus adalimumab versus placebo

Characteristics of the Study Patients and Disease Activity at Baseline

Taylor PC et al N Engl J Med 2017376652-662

Primary and Secondary Efficacy End Points

Taylor PC et al N Engl J Med 2017376652-662

Inhibition of Radiographic Progression of Structural Joint Damage at Week 24

Taylor PC et al N Engl J Med 2017376652-662

Safety and Laboratory Data Week 0 to Week 24 and Week 0 to Week 52

Taylor PC et al N Engl J Med 2017376652-662

Conclusions

bull In patients with rheumatoid arthritis who had had an inadequate response to methotrexate baricitinib was associated with significant clinical improvements as compared with placebo

bull Clinical and radiological outcomes were statistically significantly better with baricitinib than with adalimumab

Efficacy and safety of sirukumab in patients with active rheumatoid arthritis refractory

to anti-TNF therapy (SIRROUND-T) a randomised double-blind placebo-controlled

parallel-group multinational phase 3 study

Daniel Aletaha MD Clifton O Bingham MD Prof Yoshiya Tanaka MD Prasheen Agarwal PhD Regina Kurrasch MD Prof Paul P Tak

MD Sharon Popik MD

The Lancet

Volume 389 Issue 10075 Pages 1206-1217 (March 2017) DOI 101016S0140-6736(17)30401-4

Copyright copy 2017 Elsevier Ltd Terms and Conditions

Study Overview

bull Phase 3 randomized trial

bull Patients with rheumatoid arthritis on background MTX

bull Baricitinib versus adalimumab versus placebo

Characteristics of the Study Patients and Disease Activity at Baseline

Taylor PC et al N Engl J Med 2017376652-662

Primary and Secondary Efficacy End Points

Taylor PC et al N Engl J Med 2017376652-662

Inhibition of Radiographic Progression of Structural Joint Damage at Week 24

Taylor PC et al N Engl J Med 2017376652-662

Safety and Laboratory Data Week 0 to Week 24 and Week 0 to Week 52

Taylor PC et al N Engl J Med 2017376652-662

Conclusions

bull In patients with rheumatoid arthritis who had had an inadequate response to methotrexate baricitinib was associated with significant clinical improvements as compared with placebo

bull Clinical and radiological outcomes were statistically significantly better with baricitinib than with adalimumab

Efficacy and safety of sirukumab in patients with active rheumatoid arthritis refractory

to anti-TNF therapy (SIRROUND-T) a randomised double-blind placebo-controlled

parallel-group multinational phase 3 study

Daniel Aletaha MD Clifton O Bingham MD Prof Yoshiya Tanaka MD Prasheen Agarwal PhD Regina Kurrasch MD Prof Paul P Tak

MD Sharon Popik MD

The Lancet

Volume 389 Issue 10075 Pages 1206-1217 (March 2017) DOI 101016S0140-6736(17)30401-4

Copyright copy 2017 Elsevier Ltd Terms and Conditions

Characteristics of the Study Patients and Disease Activity at Baseline

Taylor PC et al N Engl J Med 2017376652-662

Primary and Secondary Efficacy End Points

Taylor PC et al N Engl J Med 2017376652-662

Inhibition of Radiographic Progression of Structural Joint Damage at Week 24

Taylor PC et al N Engl J Med 2017376652-662

Safety and Laboratory Data Week 0 to Week 24 and Week 0 to Week 52

Taylor PC et al N Engl J Med 2017376652-662

Conclusions

bull In patients with rheumatoid arthritis who had had an inadequate response to methotrexate baricitinib was associated with significant clinical improvements as compared with placebo

bull Clinical and radiological outcomes were statistically significantly better with baricitinib than with adalimumab

Efficacy and safety of sirukumab in patients with active rheumatoid arthritis refractory

to anti-TNF therapy (SIRROUND-T) a randomised double-blind placebo-controlled

parallel-group multinational phase 3 study

Daniel Aletaha MD Clifton O Bingham MD Prof Yoshiya Tanaka MD Prasheen Agarwal PhD Regina Kurrasch MD Prof Paul P Tak

MD Sharon Popik MD

The Lancet

Volume 389 Issue 10075 Pages 1206-1217 (March 2017) DOI 101016S0140-6736(17)30401-4

Copyright copy 2017 Elsevier Ltd Terms and Conditions

Primary and Secondary Efficacy End Points

Taylor PC et al N Engl J Med 2017376652-662

Inhibition of Radiographic Progression of Structural Joint Damage at Week 24

Taylor PC et al N Engl J Med 2017376652-662

Safety and Laboratory Data Week 0 to Week 24 and Week 0 to Week 52

Taylor PC et al N Engl J Med 2017376652-662

Conclusions

bull In patients with rheumatoid arthritis who had had an inadequate response to methotrexate baricitinib was associated with significant clinical improvements as compared with placebo

bull Clinical and radiological outcomes were statistically significantly better with baricitinib than with adalimumab

Efficacy and safety of sirukumab in patients with active rheumatoid arthritis refractory

to anti-TNF therapy (SIRROUND-T) a randomised double-blind placebo-controlled

parallel-group multinational phase 3 study

Daniel Aletaha MD Clifton O Bingham MD Prof Yoshiya Tanaka MD Prasheen Agarwal PhD Regina Kurrasch MD Prof Paul P Tak

MD Sharon Popik MD

The Lancet

Volume 389 Issue 10075 Pages 1206-1217 (March 2017) DOI 101016S0140-6736(17)30401-4

Copyright copy 2017 Elsevier Ltd Terms and Conditions

Inhibition of Radiographic Progression of Structural Joint Damage at Week 24

Taylor PC et al N Engl J Med 2017376652-662

Safety and Laboratory Data Week 0 to Week 24 and Week 0 to Week 52

Taylor PC et al N Engl J Med 2017376652-662

Conclusions

bull In patients with rheumatoid arthritis who had had an inadequate response to methotrexate baricitinib was associated with significant clinical improvements as compared with placebo

bull Clinical and radiological outcomes were statistically significantly better with baricitinib than with adalimumab

Efficacy and safety of sirukumab in patients with active rheumatoid arthritis refractory

to anti-TNF therapy (SIRROUND-T) a randomised double-blind placebo-controlled

parallel-group multinational phase 3 study

Daniel Aletaha MD Clifton O Bingham MD Prof Yoshiya Tanaka MD Prasheen Agarwal PhD Regina Kurrasch MD Prof Paul P Tak

MD Sharon Popik MD

The Lancet

Volume 389 Issue 10075 Pages 1206-1217 (March 2017) DOI 101016S0140-6736(17)30401-4

Copyright copy 2017 Elsevier Ltd Terms and Conditions

Safety and Laboratory Data Week 0 to Week 24 and Week 0 to Week 52

Taylor PC et al N Engl J Med 2017376652-662

Conclusions

bull In patients with rheumatoid arthritis who had had an inadequate response to methotrexate baricitinib was associated with significant clinical improvements as compared with placebo

bull Clinical and radiological outcomes were statistically significantly better with baricitinib than with adalimumab

Efficacy and safety of sirukumab in patients with active rheumatoid arthritis refractory

to anti-TNF therapy (SIRROUND-T) a randomised double-blind placebo-controlled

parallel-group multinational phase 3 study

Daniel Aletaha MD Clifton O Bingham MD Prof Yoshiya Tanaka MD Prasheen Agarwal PhD Regina Kurrasch MD Prof Paul P Tak

MD Sharon Popik MD

The Lancet

Volume 389 Issue 10075 Pages 1206-1217 (March 2017) DOI 101016S0140-6736(17)30401-4

Copyright copy 2017 Elsevier Ltd Terms and Conditions

Conclusions

bull In patients with rheumatoid arthritis who had had an inadequate response to methotrexate baricitinib was associated with significant clinical improvements as compared with placebo

bull Clinical and radiological outcomes were statistically significantly better with baricitinib than with adalimumab

Efficacy and safety of sirukumab in patients with active rheumatoid arthritis refractory

to anti-TNF therapy (SIRROUND-T) a randomised double-blind placebo-controlled

parallel-group multinational phase 3 study

Daniel Aletaha MD Clifton O Bingham MD Prof Yoshiya Tanaka MD Prasheen Agarwal PhD Regina Kurrasch MD Prof Paul P Tak

MD Sharon Popik MD

The Lancet

Volume 389 Issue 10075 Pages 1206-1217 (March 2017) DOI 101016S0140-6736(17)30401-4

Copyright copy 2017 Elsevier Ltd Terms and Conditions

Efficacy and safety of sirukumab in patients with active rheumatoid arthritis refractory

to anti-TNF therapy (SIRROUND-T) a randomised double-blind placebo-controlled

parallel-group multinational phase 3 study

Daniel Aletaha MD Clifton O Bingham MD Prof Yoshiya Tanaka MD Prasheen Agarwal PhD Regina Kurrasch MD Prof Paul P Tak

MD Sharon Popik MD

The Lancet

Volume 389 Issue 10075 Pages 1206-1217 (March 2017) DOI 101016S0140-6736(17)30401-4

Copyright copy 2017 Elsevier Ltd Terms and Conditions

Figure 1

The Lancet 2017 389 1206-1217DOI (101016S0140-6736(17)30401-4)

Copyright copy 2017 Elsevier Ltd Terms and Conditions

Figure 2

The Lancet 2017 389 1206-1217DOI (101016S0140-6736(17)30401-4)

Copyright copy 2017 Elsevier Ltd Terms and Conditions

RA NEW DATA ON OLDER

DRUGS

Original Article

Cardiovascular Safety of Celecoxib Naproxen or Ibuprofen for Arthritis

Steven E Nissen MD Neville D Yeomans MD Daniel H Solomon MD MPH Thomas F Luumlscher MD Peter Libby MD M Elaine Husni MD David Y Graham MD Jeffrey S Borer MD Lisa M Wisniewski RN Katherine E

Wolski MPH Qiuqing Wang MS Venu Menon MD Frank Ruschitzka MD Michael Gaffney PhD Bruce Beckerman MD Manuela F Berger MD Weihang

Bao PhD A Michael Lincoff MD for the PRECISION Trial Investigators

N Engl J MedVolume ()2519-2529December 29 2016

Study Overview

bull Randomized trial

bull Osteoarthritis or rheumatoid arthritis at increased cardiovascular risk

bull Celecoxib versus naproxen versus ibuprofen

bull Primary outcome cardiovascular safety

Time-to-Event Analysis for Primary and Secondary Outcomes

Nissen SE et al N Engl J Med 20162519-2529

Baseline Characteristics of Patients in the Intention-to-Treat Population

Nissen SE et al N Engl J Med 20162519-2529

Adjudicated Outcomes in the Intention-to-Treat Population

Nissen SE et al N Engl J Med 20162519-2529

Adjudicated Outcomes in the On-Treatment Population

Nissen SE et al N Engl J Med 20162519-2529

Conclusions

bull At moderate doses celecoxib was found to be noninferior to ibuprofen or naproxen with regard to cardiovascular safety (primary outcome)

bull In secondary outcomes celecoxib was generally superior to ibuprofen in serious gastrointestinal and renal side-effects

bull Comparisons with naproxen yielded equivocal results

bull A limitation of the study is that most patients were on the 100 mg bid dosage of celecoxib

Head-to-head comparison of certolizumab pegol versus adalimumab in rheumatoid

arthritis 2-year efficacy and safety results from the randomised EXXELERATE study

Prof Josef S Smolen MD Prof Gerd-Ruumldiger Burmester MD Prof Bernard Combe MD PhD Prof Jeffrey R Curtis MD Stephen Hall

MD Boulos Haraoui MD Prof Ronald van Vollenhoven MD Christopher Cioffi PhD Ceacutecile Ecoffet PharmD Leon Gervitz PhD Lucian

Ionescu MD Luke Peterson MS Prof Roy Fleischmann MD

The Lancet

Volume 388 Issue 10061 Pages 2763-2774 (December 2016) DOI 101016S0140-6736(16)31651-8

Copyright copy 2016 Elsevier Ltd Terms and Conditions

Original Article

Cardiovascular Safety of Celecoxib Naproxen or Ibuprofen for Arthritis

Steven E Nissen MD Neville D Yeomans MD Daniel H Solomon MD MPH Thomas F Luumlscher MD Peter Libby MD M Elaine Husni MD David Y Graham MD Jeffrey S Borer MD Lisa M Wisniewski RN Katherine E

Wolski MPH Qiuqing Wang MS Venu Menon MD Frank Ruschitzka MD Michael Gaffney PhD Bruce Beckerman MD Manuela F Berger MD Weihang

Bao PhD A Michael Lincoff MD for the PRECISION Trial Investigators

N Engl J MedVolume ()2519-2529December 29 2016

Study Overview

bull Randomized trial

bull Osteoarthritis or rheumatoid arthritis at increased cardiovascular risk

bull Celecoxib versus naproxen versus ibuprofen

bull Primary outcome cardiovascular safety

Time-to-Event Analysis for Primary and Secondary Outcomes

Nissen SE et al N Engl J Med 20162519-2529

Baseline Characteristics of Patients in the Intention-to-Treat Population

Nissen SE et al N Engl J Med 20162519-2529

Adjudicated Outcomes in the Intention-to-Treat Population

Nissen SE et al N Engl J Med 20162519-2529

Adjudicated Outcomes in the On-Treatment Population

Nissen SE et al N Engl J Med 20162519-2529

Conclusions

bull At moderate doses celecoxib was found to be noninferior to ibuprofen or naproxen with regard to cardiovascular safety (primary outcome)

bull In secondary outcomes celecoxib was generally superior to ibuprofen in serious gastrointestinal and renal side-effects

bull Comparisons with naproxen yielded equivocal results

bull A limitation of the study is that most patients were on the 100 mg bid dosage of celecoxib

Head-to-head comparison of certolizumab pegol versus adalimumab in rheumatoid

arthritis 2-year efficacy and safety results from the randomised EXXELERATE study

Prof Josef S Smolen MD Prof Gerd-Ruumldiger Burmester MD Prof Bernard Combe MD PhD Prof Jeffrey R Curtis MD Stephen Hall

MD Boulos Haraoui MD Prof Ronald van Vollenhoven MD Christopher Cioffi PhD Ceacutecile Ecoffet PharmD Leon Gervitz PhD Lucian

Ionescu MD Luke Peterson MS Prof Roy Fleischmann MD

The Lancet

Volume 388 Issue 10061 Pages 2763-2774 (December 2016) DOI 101016S0140-6736(16)31651-8

Copyright copy 2016 Elsevier Ltd Terms and Conditions

Study Overview

bull Randomized trial

bull Osteoarthritis or rheumatoid arthritis at increased cardiovascular risk

bull Celecoxib versus naproxen versus ibuprofen

bull Primary outcome cardiovascular safety

Time-to-Event Analysis for Primary and Secondary Outcomes

Nissen SE et al N Engl J Med 20162519-2529

Baseline Characteristics of Patients in the Intention-to-Treat Population

Nissen SE et al N Engl J Med 20162519-2529

Adjudicated Outcomes in the Intention-to-Treat Population

Nissen SE et al N Engl J Med 20162519-2529

Adjudicated Outcomes in the On-Treatment Population

Nissen SE et al N Engl J Med 20162519-2529

Conclusions

bull At moderate doses celecoxib was found to be noninferior to ibuprofen or naproxen with regard to cardiovascular safety (primary outcome)

bull In secondary outcomes celecoxib was generally superior to ibuprofen in serious gastrointestinal and renal side-effects

bull Comparisons with naproxen yielded equivocal results

bull A limitation of the study is that most patients were on the 100 mg bid dosage of celecoxib

Head-to-head comparison of certolizumab pegol versus adalimumab in rheumatoid

arthritis 2-year efficacy and safety results from the randomised EXXELERATE study

Prof Josef S Smolen MD Prof Gerd-Ruumldiger Burmester MD Prof Bernard Combe MD PhD Prof Jeffrey R Curtis MD Stephen Hall

MD Boulos Haraoui MD Prof Ronald van Vollenhoven MD Christopher Cioffi PhD Ceacutecile Ecoffet PharmD Leon Gervitz PhD Lucian

Ionescu MD Luke Peterson MS Prof Roy Fleischmann MD

The Lancet

Volume 388 Issue 10061 Pages 2763-2774 (December 2016) DOI 101016S0140-6736(16)31651-8

Copyright copy 2016 Elsevier Ltd Terms and Conditions

Time-to-Event Analysis for Primary and Secondary Outcomes

Nissen SE et al N Engl J Med 20162519-2529

Baseline Characteristics of Patients in the Intention-to-Treat Population

Nissen SE et al N Engl J Med 20162519-2529

Adjudicated Outcomes in the Intention-to-Treat Population

Nissen SE et al N Engl J Med 20162519-2529

Adjudicated Outcomes in the On-Treatment Population

Nissen SE et al N Engl J Med 20162519-2529

Conclusions

bull At moderate doses celecoxib was found to be noninferior to ibuprofen or naproxen with regard to cardiovascular safety (primary outcome)

bull In secondary outcomes celecoxib was generally superior to ibuprofen in serious gastrointestinal and renal side-effects

bull Comparisons with naproxen yielded equivocal results

bull A limitation of the study is that most patients were on the 100 mg bid dosage of celecoxib

Head-to-head comparison of certolizumab pegol versus adalimumab in rheumatoid

arthritis 2-year efficacy and safety results from the randomised EXXELERATE study

Prof Josef S Smolen MD Prof Gerd-Ruumldiger Burmester MD Prof Bernard Combe MD PhD Prof Jeffrey R Curtis MD Stephen Hall

MD Boulos Haraoui MD Prof Ronald van Vollenhoven MD Christopher Cioffi PhD Ceacutecile Ecoffet PharmD Leon Gervitz PhD Lucian

Ionescu MD Luke Peterson MS Prof Roy Fleischmann MD

The Lancet

Volume 388 Issue 10061 Pages 2763-2774 (December 2016) DOI 101016S0140-6736(16)31651-8

Copyright copy 2016 Elsevier Ltd Terms and Conditions

Baseline Characteristics of Patients in the Intention-to-Treat Population

Nissen SE et al N Engl J Med 20162519-2529

Adjudicated Outcomes in the Intention-to-Treat Population

Nissen SE et al N Engl J Med 20162519-2529

Adjudicated Outcomes in the On-Treatment Population

Nissen SE et al N Engl J Med 20162519-2529

Conclusions

bull At moderate doses celecoxib was found to be noninferior to ibuprofen or naproxen with regard to cardiovascular safety (primary outcome)

bull In secondary outcomes celecoxib was generally superior to ibuprofen in serious gastrointestinal and renal side-effects

bull Comparisons with naproxen yielded equivocal results

bull A limitation of the study is that most patients were on the 100 mg bid dosage of celecoxib

Head-to-head comparison of certolizumab pegol versus adalimumab in rheumatoid

arthritis 2-year efficacy and safety results from the randomised EXXELERATE study

Prof Josef S Smolen MD Prof Gerd-Ruumldiger Burmester MD Prof Bernard Combe MD PhD Prof Jeffrey R Curtis MD Stephen Hall

MD Boulos Haraoui MD Prof Ronald van Vollenhoven MD Christopher Cioffi PhD Ceacutecile Ecoffet PharmD Leon Gervitz PhD Lucian

Ionescu MD Luke Peterson MS Prof Roy Fleischmann MD

The Lancet

Volume 388 Issue 10061 Pages 2763-2774 (December 2016) DOI 101016S0140-6736(16)31651-8

Copyright copy 2016 Elsevier Ltd Terms and Conditions

Adjudicated Outcomes in the Intention-to-Treat Population

Nissen SE et al N Engl J Med 20162519-2529

Adjudicated Outcomes in the On-Treatment Population

Nissen SE et al N Engl J Med 20162519-2529

Conclusions

bull At moderate doses celecoxib was found to be noninferior to ibuprofen or naproxen with regard to cardiovascular safety (primary outcome)

bull In secondary outcomes celecoxib was generally superior to ibuprofen in serious gastrointestinal and renal side-effects

bull Comparisons with naproxen yielded equivocal results

bull A limitation of the study is that most patients were on the 100 mg bid dosage of celecoxib

Head-to-head comparison of certolizumab pegol versus adalimumab in rheumatoid

arthritis 2-year efficacy and safety results from the randomised EXXELERATE study

Prof Josef S Smolen MD Prof Gerd-Ruumldiger Burmester MD Prof Bernard Combe MD PhD Prof Jeffrey R Curtis MD Stephen Hall

MD Boulos Haraoui MD Prof Ronald van Vollenhoven MD Christopher Cioffi PhD Ceacutecile Ecoffet PharmD Leon Gervitz PhD Lucian

Ionescu MD Luke Peterson MS Prof Roy Fleischmann MD

The Lancet

Volume 388 Issue 10061 Pages 2763-2774 (December 2016) DOI 101016S0140-6736(16)31651-8

Copyright copy 2016 Elsevier Ltd Terms and Conditions

Adjudicated Outcomes in the On-Treatment Population

Nissen SE et al N Engl J Med 20162519-2529

Conclusions

bull At moderate doses celecoxib was found to be noninferior to ibuprofen or naproxen with regard to cardiovascular safety (primary outcome)

bull In secondary outcomes celecoxib was generally superior to ibuprofen in serious gastrointestinal and renal side-effects

bull Comparisons with naproxen yielded equivocal results

bull A limitation of the study is that most patients were on the 100 mg bid dosage of celecoxib

Head-to-head comparison of certolizumab pegol versus adalimumab in rheumatoid

arthritis 2-year efficacy and safety results from the randomised EXXELERATE study

Prof Josef S Smolen MD Prof Gerd-Ruumldiger Burmester MD Prof Bernard Combe MD PhD Prof Jeffrey R Curtis MD Stephen Hall

MD Boulos Haraoui MD Prof Ronald van Vollenhoven MD Christopher Cioffi PhD Ceacutecile Ecoffet PharmD Leon Gervitz PhD Lucian

Ionescu MD Luke Peterson MS Prof Roy Fleischmann MD

The Lancet

Volume 388 Issue 10061 Pages 2763-2774 (December 2016) DOI 101016S0140-6736(16)31651-8

Copyright copy 2016 Elsevier Ltd Terms and Conditions

Conclusions

bull At moderate doses celecoxib was found to be noninferior to ibuprofen or naproxen with regard to cardiovascular safety (primary outcome)

bull In secondary outcomes celecoxib was generally superior to ibuprofen in serious gastrointestinal and renal side-effects

bull Comparisons with naproxen yielded equivocal results

bull A limitation of the study is that most patients were on the 100 mg bid dosage of celecoxib

Head-to-head comparison of certolizumab pegol versus adalimumab in rheumatoid

arthritis 2-year efficacy and safety results from the randomised EXXELERATE study

Prof Josef S Smolen MD Prof Gerd-Ruumldiger Burmester MD Prof Bernard Combe MD PhD Prof Jeffrey R Curtis MD Stephen Hall

MD Boulos Haraoui MD Prof Ronald van Vollenhoven MD Christopher Cioffi PhD Ceacutecile Ecoffet PharmD Leon Gervitz PhD Lucian

Ionescu MD Luke Peterson MS Prof Roy Fleischmann MD

The Lancet

Volume 388 Issue 10061 Pages 2763-2774 (December 2016) DOI 101016S0140-6736(16)31651-8

Copyright copy 2016 Elsevier Ltd Terms and Conditions

Head-to-head comparison of certolizumab pegol versus adalimumab in rheumatoid

arthritis 2-year efficacy and safety results from the randomised EXXELERATE study

Prof Josef S Smolen MD Prof Gerd-Ruumldiger Burmester MD Prof Bernard Combe MD PhD Prof Jeffrey R Curtis MD Stephen Hall

MD Boulos Haraoui MD Prof Ronald van Vollenhoven MD Christopher Cioffi PhD Ceacutecile Ecoffet PharmD Leon Gervitz PhD Lucian

Ionescu MD Luke Peterson MS Prof Roy Fleischmann MD

The Lancet

Volume 388 Issue 10061 Pages 2763-2774 (December 2016) DOI 101016S0140-6736(16)31651-8

Copyright copy 2016 Elsevier Ltd Terms and Conditions

Figure 1

The Lancet 2016 388 2763-2774DOI (101016S0140-6736(16)31651-8)

Copyright copy 2016 Elsevier Ltd Terms and Conditions

Figure 2

The Lancet 2016 388 2763-2774DOI (101016S0140-6736(16)31651-8)

Copyright copy 2016 Elsevier Ltd Terms and Conditions

Figure 3

The Lancet 2016 388 2763-2774DOI (101016S0140-6736(16)31651-8)

Copyright copy 2016 Elsevier Ltd Terms and Conditions

Figure 4

The Lancet 2016 388 2763-2774DOI (101016S0140-6736(16)31651-8)

Copyright copy 2016 Elsevier Ltd Terms and Conditions

Figure 5

The Lancet 2016 388 2763-2774DOI (101016S0140-6736(16)31651-8)

Copyright copy 2016 Elsevier Ltd Terms and Conditions

RA BIOSIMILARS

httpwwwmundipharmacomdocsdefault-sourcedefault-document-

library161019-ueg-press-release-finalpdfsfvrsn=0

httpwwwmundipharmacomdocsdefault-sourcedefault-document-

library161019-ueg-press-release-finalpdfsfvrsn=0

RA TREATMENT

STRATEGIES

RA TREATMENT

STRATEGIES ndash FIRST-LINE

Early rheumatoid arthritis treated with tocilizumab methotrexate or their combination

(U-Act-Early) a multicentre randomised double-blind double-dummy strategy trial

Prof Johannes W J Bijlsma MD Paco M J Welsing PhD Thasia G Woodworth MD Leonie M Middelink MSc Attila Pethouml-Schramm

MD Corrado Bernasconi MD Michelle E A Borm PhD Cornelis H Wortel MD Evert Jan ter Borg MD Z Nazira Jahangier MD Willemijn

H van der Laan MD George A W Bruyn MD Paul Baudoin MD Siska Wijngaarden MD Petra A J M Vos MD Reinhard Bos MD

Mirian J F Starmans MD Eduard N Griep MD Joanna R M Griep-Wentink MD Cornelia F Allaart MD Anton H M Heurkens MD Xavier

M Teitsma MSc Janneke Tekstra MD Anne Carien A Marijnissen PhD Prof Floris P J Lafeber PhD Dr Johannes W G Jacobs MD

The Lancet

Volume 388 Issue 10042 Pages 343-355 (July 2016) DOI 101016S0140-6736(16)30363-4

Copyright copy 2016 Elsevier Ltd Terms and Conditions

RA TREATMENT

STRATEGIES ndash FIRST-LINE

Early rheumatoid arthritis treated with tocilizumab methotrexate or their combination

(U-Act-Early) a multicentre randomised double-blind double-dummy strategy trial

Prof Johannes W J Bijlsma MD Paco M J Welsing PhD Thasia G Woodworth MD Leonie M Middelink MSc Attila Pethouml-Schramm

MD Corrado Bernasconi MD Michelle E A Borm PhD Cornelis H Wortel MD Evert Jan ter Borg MD Z Nazira Jahangier MD Willemijn

H van der Laan MD George A W Bruyn MD Paul Baudoin MD Siska Wijngaarden MD Petra A J M Vos MD Reinhard Bos MD

Mirian J F Starmans MD Eduard N Griep MD Joanna R M Griep-Wentink MD Cornelia F Allaart MD Anton H M Heurkens MD Xavier

M Teitsma MSc Janneke Tekstra MD Anne Carien A Marijnissen PhD Prof Floris P J Lafeber PhD Dr Johannes W G Jacobs MD

The Lancet

Volume 388 Issue 10042 Pages 343-355 (July 2016) DOI 101016S0140-6736(16)30363-4

Copyright copy 2016 Elsevier Ltd Terms and Conditions

Early rheumatoid arthritis treated with tocilizumab methotrexate or their combination

(U-Act-Early) a multicentre randomised double-blind double-dummy strategy trial

Prof Johannes W J Bijlsma MD Paco M J Welsing PhD Thasia G Woodworth MD Leonie M Middelink MSc Attila Pethouml-Schramm

MD Corrado Bernasconi MD Michelle E A Borm PhD Cornelis H Wortel MD Evert Jan ter Borg MD Z Nazira Jahangier MD Willemijn

H van der Laan MD George A W Bruyn MD Paul Baudoin MD Siska Wijngaarden MD Petra A J M Vos MD Reinhard Bos MD

Mirian J F Starmans MD Eduard N Griep MD Joanna R M Griep-Wentink MD Cornelia F Allaart MD Anton H M Heurkens MD Xavier

M Teitsma MSc Janneke Tekstra MD Anne Carien A Marijnissen PhD Prof Floris P J Lafeber PhD Dr Johannes W G Jacobs MD

The Lancet

Volume 388 Issue 10042 Pages 343-355 (July 2016) DOI 101016S0140-6736(16)30363-4

Copyright copy 2016 Elsevier Ltd Terms and Conditions

Figure 1

The Lancet 2016 388 343-355DOI (101016S0140-6736(16)30363-4)

Copyright copy 2016 Elsevier Ltd Terms and Conditions

Figure 2

The Lancet 2016 388 343-355DOI (101016S0140-6736(16)30363-4)

Copyright copy 2016 Elsevier Ltd Terms and Conditions

Figure 3

The Lancet 2016 388 343-355DOI (101016S0140-6736(16)30363-4)

Copyright copy 2016 Elsevier Ltd Terms and Conditions

RA TREATMENT

STRATEGIES ndash SECOND-LINE

Tumour necrosis factor inhibition versus rituximab for patients with rheumatoid arthritis

who require biological treatment (ORBIT) an open-label randomised controlled non-

inferiority trial

Dr Duncan Porter MD Jurgen van Melckebeke BSc James Dale PhD C Martina Messow PhD Alexander McConnachie PhD Andrew

Walker PhD Robin Munro MRCP John McLaren MRCP Euan McRorie FRCP Jon Packham DM Prof Christopher D Buckley DPhil

John Harvie FRCP Prof Peter Taylor PhD Prof Ernest Choy MD Prof Costantino Pitzalis PhD Prof Iain B McInnes PhD

The Lancet

Volume 388 Issue 10041 Pages 239-247 (July 2016) DOI 101016S0140-6736(16)00380-9

Copyright copy 2016 Elsevier Ltd Terms and Conditions

Tumour necrosis factor inhibition versus rituximab for patients with rheumatoid arthritis

who require biological treatment (ORBIT) an open-label randomised controlled non-

inferiority trial

Dr Duncan Porter MD Jurgen van Melckebeke BSc James Dale PhD C Martina Messow PhD Alexander McConnachie PhD Andrew

Walker PhD Robin Munro MRCP John McLaren MRCP Euan McRorie FRCP Jon Packham DM Prof Christopher D Buckley DPhil

John Harvie FRCP Prof Peter Taylor PhD Prof Ernest Choy MD Prof Costantino Pitzalis PhD Prof Iain B McInnes PhD

The Lancet

Volume 388 Issue 10041 Pages 239-247 (July 2016) DOI 101016S0140-6736(16)00380-9

Copyright copy 2016 Elsevier Ltd Terms and Conditions

Figure 1

The Lancet 2016 388 239-247DOI (101016S0140-6736(16)00380-9)

Copyright copy 2016 Elsevier Ltd Terms and Conditions

Figure 2

The Lancet 2016 388 239-247DOI (101016S0140-6736(16)00380-9)

Copyright copy 2016 Elsevier Ltd Terms and Conditions

RA TREATMENT

STRATEGIES ndash THIRD-LINE

Date of download 4112017

From NonndashTNF-Targeted Biologic vs a Second Anti-TNF Drug to Treat Rheumatoid Arthritis in Patients With

Insufficient Response to a First Anti-TNF DrugA Randomized Clinical Trial

JAMA 2016316(11)1172-1180 doi101001jama201613512

Constrained longitudinal data analyses were used for between-group comparisons for DAS28-ESR and HAQ For DAS-28-ESR the

12-week P value was 008 24- week Pthinsp=thinsp004 and 52-week Pthinsp=thinsp01 for HAQ the 12-week P value was09 24-week Pthinsp=thinsp44 and

52-week Pthinsp=thinsp75 Data markers represent the mean and error bars 95 CIs

Figure Legend

SLE TREATMENT

Efficacy and tolerability of repository corticotropin injection in patients

with persistently active SLE results of a phase 4 randomised controlled

pilot study

Furie R1 Mitrane M2 Zhao E3 Das M3 Li D3 Becker PM3

Lupus Sci Med 2016 Oct 213(1)e000180 eCollection 2016

Date of download 4112017

From NonndashTNF-Targeted Biologic vs a Second Anti-TNF Drug to Treat Rheumatoid Arthritis in Patients With

Insufficient Response to a First Anti-TNF DrugA Randomized Clinical Trial

JAMA 2016316(11)1172-1180 doi101001jama201613512

Constrained longitudinal data analyses were used for between-group comparisons for DAS28-ESR and HAQ For DAS-28-ESR the

12-week P value was 008 24- week Pthinsp=thinsp004 and 52-week Pthinsp=thinsp01 for HAQ the 12-week P value was09 24-week Pthinsp=thinsp44 and

52-week Pthinsp=thinsp75 Data markers represent the mean and error bars 95 CIs

Figure Legend

SLE TREATMENT

Efficacy and tolerability of repository corticotropin injection in patients

with persistently active SLE results of a phase 4 randomised controlled

pilot study

Furie R1 Mitrane M2 Zhao E3 Das M3 Li D3 Becker PM3

Lupus Sci Med 2016 Oct 213(1)e000180 eCollection 2016

SLE TREATMENT

Efficacy and tolerability of repository corticotropin injection in patients

with persistently active SLE results of a phase 4 randomised controlled

pilot study

Furie R1 Mitrane M2 Zhao E3 Das M3 Li D3 Becker PM3

Lupus Sci Med 2016 Oct 213(1)e000180 eCollection 2016

Efficacy and tolerability of repository corticotropin injection in patients

with persistently active SLE results of a phase 4 randomised controlled

pilot study

Furie R1 Mitrane M2 Zhao E3 Das M3 Li D3 Becker PM3

Lupus Sci Med 2016 Oct 213(1)e000180 eCollection 2016

Rivaroxaban versus warfarin to treat patients with thrombotic antiphospholipid

syndrome with or without systemic lupus erythematosus (RAPS) a randomised

controlled open-label phase 23 non-inferiority trial

Dr Hannah Cohen MD Prof Beverley J Hunt MD Maria Efthymiou PhD Deepa R J Arachchillage MD Ian J Mackie PhD Simon

Clawson BSc Yvonne Sylvestre MSc Prof Samuel J Machin FRCP Maria L Bertolaccini PhD Maria Ruiz-Castellano MD Nicola

Muirhead PhD Prof Caroline J Doreacute BSc Prof Munther Khamashta MD Prof David A Isenberg MD

The Lancet Haematology

Volume 3 Issue 9 Pages e426-e436 (September 2016) DOI 101016S2352-3026(16)30079-5

Copyright copy 2016 The Author(s) Published by Elsevier Ltd This is an Open Access article under the CC

BY license Terms and Conditions

Figure 1

The Lancet Haematology 2016 3 e426-e436DOI (101016S2352-3026(16)30079-5) Copyright copy 2016 The Author(s) Published by Elsevier Ltd This is an Open Access article under the CC

BY license Terms and Conditions

Figure 2

The Lancet Haematology 2016 3 e426-e436DOI (101016S2352-3026(16)30079-5) Copyright copy 2016 The Author(s) Published by Elsevier Ltd This is an Open Access article under the CC

BY license Terms and Conditions

Figure 3

The Lancet Haematology 2016 3 e426-e436DOI (101016S2352-3026(16)30079-5) Copyright copy 2016 The Author(s) Published by Elsevier Ltd This is an Open Access article under the CC

BY license Terms and Conditions