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Safety and effectiveness of upadacitinib or adalimumab plus methotrexate in patients with rheumatoid arthritis over 48 weeks with switch to alternate therapy in patients with insufficient response.
Ann Rheum Dis. 2019 11; 78(11):1454-1462.AR

Abstract

BACKGROUND

In SELECT-COMPARE, a randomised double-blind study, upadacitinib 15 mg once daily was superior to placebo or adalimumab on background methotrexate (MTX) for treating rheumatoid arthritis signs and symptoms and inhibited radiographical progression versus placebo at 26 weeks. Here we report 48-week safety and efficacy in patients who continued their original medication or were rescued to the alternative medication for insufficient response.

METHODS

Patients on MTX received upadacitinib 15 mg, placebo or adalimumab for 48 weeks. Rescue without washout, from placebo or adalimumab to upadacitinib or upadacitinib to adalimumab occurred if patients had <20% improvement in tender joint count (TJC) or swollen joint count (SJC) (weeks 14/18/22) or Clinical Disease Activity Index (CDAI) >10 (week 26); remaining placebo patients were switched to upadacitinib at week 26. Efficacy was analysed by randomised group (non-responder imputation), as well as separately for rescued patients (as observed). Treatment-emergent adverse events per 100 patient-years were summarised.

RESULTS

Consistent with responses through week 26, from weeks 26 to 48, responses by randomised group including low disease activity, clinical remission and improvements in pain and function remained superior for upadacitinib versus adalimumab; radiographical progression remained lower for upadacitinib versus placebo (linear extrapolation). Although both switch groups responded, a higher proportion of patients rescued to upadacitinib from adalimumab achieved CDAI ≤10 at 6 months postswitch versus patients rescued from upadacitinib to adalimumab. Safety at week 48 was comparable to week 26.

CONCLUSION

Upadacitinib+MTX demonstrated superior clinical and functional responses versus adalimumab+MTX and maintained inhibition of structural damage versus placebo+MTX through week 48. Patients with an insufficient response to adalimumab or upadacitinib safely achieved clinically meaningful responses after switching to the alternative medication without washout.

Authors+Show Affiliations

Medicine, University of Texas Southwestern, Dallas, Texas, USA rfleischmann@arthdocs.com.Rheumatology, Stanford University, Palo Alto, California, USA.Immunology Clinical Development, Abbvie Inc, North Chicago, Illinois, USA.Organización Medica de Investigación, Buenos Aires, Argentina.Universite Laval Faculte de medecine, Quebec City, Quebec, Canada. Centre de recherche du CHU de Québec, Université Laval, Quebec City, Québec, Canada.Spire Sciences Inc, Boca Raton, Florida, USA.Pôle de Recherche en Rhumatologie, Institut de Recherche Experimentale et Clinique, Universitde Louvain, UCL, Brussels, Belgium.Cabrini Medical Center, Malvern, Victoria, Australia.Data and Statistical Sciences, AbbVie Inc, North Chicago, Illinois, USA.Immunology Clinical Development, Abbvie Inc, North Chicago, Illinois, USA.

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31362993

Citation

Fleischmann, Roy M., et al. "Safety and Effectiveness of Upadacitinib or Adalimumab Plus Methotrexate in Patients With Rheumatoid Arthritis Over 48 Weeks With Switch to Alternate Therapy in Patients With Insufficient Response." Annals of the Rheumatic Diseases, vol. 78, no. 11, 2019, pp. 1454-1462.
Fleischmann RM, Genovese MC, Enejosa JV, et al. Safety and effectiveness of upadacitinib or adalimumab plus methotrexate in patients with rheumatoid arthritis over 48 weeks with switch to alternate therapy in patients with insufficient response. Ann Rheum Dis. 2019;78(11):1454-1462.
Fleischmann, R. M., Genovese, M. C., Enejosa, J. V., Mysler, E., Bessette, L., Peterfy, C., Durez, P., Ostor, A., Li, Y., & Song, I. H. (2019). Safety and effectiveness of upadacitinib or adalimumab plus methotrexate in patients with rheumatoid arthritis over 48 weeks with switch to alternate therapy in patients with insufficient response. Annals of the Rheumatic Diseases, 78(11), 1454-1462. https://doi.org/10.1136/annrheumdis-2019-215764
Fleischmann RM, et al. Safety and Effectiveness of Upadacitinib or Adalimumab Plus Methotrexate in Patients With Rheumatoid Arthritis Over 48 Weeks With Switch to Alternate Therapy in Patients With Insufficient Response. Ann Rheum Dis. 2019;78(11):1454-1462. PubMed PMID: 31362993.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Safety and effectiveness of upadacitinib or adalimumab plus methotrexate in patients with rheumatoid arthritis over 48 weeks with switch to alternate therapy in patients with insufficient response. AU - Fleischmann,Roy M, AU - Genovese,Mark C, AU - Enejosa,Jeffrey V, AU - Mysler,Eduardo, AU - Bessette,Louis, AU - Peterfy,Charles, AU - Durez,Patrick, AU - Ostor,Andrew, AU - Li,Yihan, AU - Song,In-Ho, Y1 - 2019/07/30/ PY - 2019/05/22/received PY - 2019/07/13/revised PY - 2019/07/15/accepted PY - 2019/8/1/pubmed PY - 2020/4/11/medline PY - 2019/8/1/entrez KW - dmards (biologic) KW - dmards (synthetic) KW - methotrexate KW - rheumatoid arthritis SP - 1454 EP - 1462 JF - Annals of the rheumatic diseases JO - Ann. Rheum. Dis. VL - 78 IS - 11 N2 - BACKGROUND: In SELECT-COMPARE, a randomised double-blind study, upadacitinib 15 mg once daily was superior to placebo or adalimumab on background methotrexate (MTX) for treating rheumatoid arthritis signs and symptoms and inhibited radiographical progression versus placebo at 26 weeks. Here we report 48-week safety and efficacy in patients who continued their original medication or were rescued to the alternative medication for insufficient response. METHODS: Patients on MTX received upadacitinib 15 mg, placebo or adalimumab for 48 weeks. Rescue without washout, from placebo or adalimumab to upadacitinib or upadacitinib to adalimumab occurred if patients had <20% improvement in tender joint count (TJC) or swollen joint count (SJC) (weeks 14/18/22) or Clinical Disease Activity Index (CDAI) >10 (week 26); remaining placebo patients were switched to upadacitinib at week 26. Efficacy was analysed by randomised group (non-responder imputation), as well as separately for rescued patients (as observed). Treatment-emergent adverse events per 100 patient-years were summarised. RESULTS: Consistent with responses through week 26, from weeks 26 to 48, responses by randomised group including low disease activity, clinical remission and improvements in pain and function remained superior for upadacitinib versus adalimumab; radiographical progression remained lower for upadacitinib versus placebo (linear extrapolation). Although both switch groups responded, a higher proportion of patients rescued to upadacitinib from adalimumab achieved CDAI ≤10 at 6 months postswitch versus patients rescued from upadacitinib to adalimumab. Safety at week 48 was comparable to week 26. CONCLUSION: Upadacitinib+MTX demonstrated superior clinical and functional responses versus adalimumab+MTX and maintained inhibition of structural damage versus placebo+MTX through week 48. Patients with an insufficient response to adalimumab or upadacitinib safely achieved clinically meaningful responses after switching to the alternative medication without washout. SN - 1468-2060 UR - https://www.unboundmedicine.com/medline/citation/31362993/Safety_and_effectiveness_of_upadacitinib_or_adalimumab_plus_methotrexate_in_patients_with_rheumatoid_arthritis_over_48_weeks_with_switch_to_alternate_therapy_in_patients_with_insufficient_response_ L2 - http://ard.bmj.com/cgi/pmidlookup?view=long&amp;pmid=31362993 DB - PRIME DP - Unbound Medicine ER -