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January 2021 - Andreas Kerschbaumer

Dr. Andreas Kerschbaumer

MedUni Wien RESEARCHER OF THE MONTH January 2021


Efficacy Outcomes in Phase 2 and Phase 3 Randomized Controlled Trials in Rheumatology

Phase 3 trials are the mainstay of drug development across medicine but have often not met expectations set by preceding phase 2 studies. A systematic meta-analysis evaluated all randomized controlled, double-blind trials investigating targeted disease-modifying anti-rheumatic drugs in rheumatoid and psoriatic arthritis. Primary outcomes of American College of Rheumatology (ACR) 20 responses were compared by mixed-model logistic regression, including exploration of potential determinants of efficacy overestimation. In rheumatoid arthritis, phase 2 trial outcomes systematically overestimated subsequent phase 3 results, with similar (but not significant) data for psoriatic arthritis trials. Differences in inclusion criteria largely explained the observed differences in efficacy findings. These findings have implications for all stakeholders in drug development and testing, as well as potential ethical implications.

Selected Literature

  1. Kerschbaumer A, Smolen JS, Herkner H, et al. Efficacy outcomes in phase 2 and phase 3 randomized controlled trials in rheumatology. Nat Med Published Online First: 20 April 2020. doi:10.1038/s41591-020-0833-4

  2. Genovese MC, Lee E, Satterwhite J, et al. A phase 2 dose-ranging study of subcutaneous tabalumab for the treatment of patients with active rheumatoid arthritis and an inadequate response to methotrexate. Ann Rheum Dis 2013;72:1453–1460. doi:10.1136/annrheumdis-2012-202864

  3. Genovese MC, Kavanaugh A, Weinblatt ME, et al. An oral Syk kinase inhibitor in the treatment of rheumatoid arthritis: a three-month randomized, placebo-controlled, phase II study in patients with active rheumatoid arthritis that did not respond to biologic agents. Arthritis Rheum 2011;63:337–345. doi:10.1002/art.30114

  4. Strand V. Minimizing efficacy differences between phase II and III RCTs. Nat Rev Rheumatol 2020;16:359–360. doi:10.1038/s41584-020-0446-9

  5. Kerschbaumer A, Baker D, Smolen JS, et al. The effects of structural damage on functional disability in psoriatic arthritis. Ann Rheum Dis 2017;76:2038–2045. doi:10.1136/annrheumdis-2017-211433

  6. Kerschbaumer A, Sepriano A, Smolen JS, et al. Efficacy of pharmacological treatment in rheumatoid arthritis: a systematic literature research informing the 2019 update of the EULAR recommendations for management of rheumatoid arthritis. Ann Rheum Dis Published Online First: 7 February 2020. doi:10.1136/annrheumdis-2019-216656

  7. Sepriano A, Kerschbaumer A, Smolen JS, et al. Safety of synthetic and biological DMARDs: a systematic literature review informing the 2019 update of the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis 2020;79:760–770. doi:10.1136/annrheumdis-2019-216653

  8. Smolen JS, Landewé RBM, Bijlsma JWJ, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis 2020;79:685–699. doi:10.1136/annrheumdis-2019-216655

  9. Kerschbaumer A, Smolen JS, Dougados M, et al. Pharmacological treatment of psoriatic arthritis: a systematic literature research for the 2019 update of the EULAR recommendations for the management of psoriatic arthritis. Ann Rheum Dis 2020;79:778–786. doi:10.1136/annrheumdis-2020-217163

  10. Gossec L, Baraliakos X, Kerschbaumer A, et al. EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2019 update. Ann Rheum Dis 2020;79:700–712. doi:10.1136/annrheumdis-2020-217159


Dr. Andreas Kerschbaumer

Dr. Andreas Kerschbaumer
Medizinische Universität Wien
Universitätsklinik für Innere Medizin III
Klinische Abteilung für Rheumatologie
Währinger Gürtel 18-20
1090 Wien

T: +43 (0)1 40400-43000
andreas.kerschbaumer@meduniwien.ac.at