Dose reduction of baricitinib in patients with rheumatoid arthritis achieving sustained disease control: Results of a prospective study

Tsutomu Takeuchi, Mark C. Genovese, Boulos Haraoui, Zhanguo Li, Li Xie, Rena Klar, Ana Pinto-Correia, Susan Otawa, Pedro Lopez-Romero, Inmaculada De La Torre, William Macias, Terence P. Rooney, Josef S. Smolen

Research output: Contribution to journalArticle

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Abstract

Objectives: This study investigated the effects of dose step-down in patients with rheumatoid arthritis (RA) who achieved sustained disease control with baricitinib 4 mg once a day. Methods: Patients who completed a baricitinib phase 3 study could enter a long-term extension (LTE). In the LTE, patients who received baricitinib 4 mg for ≥15 months and maintained CDAI low disease activity (LDA) or remission (REM) were blindly randomised to continue 4 mg or taper to 2 mg. Patients could rescue (to 4 mg) if needed. Efficacy and safety were assessed through 48 weeks. Results: Patients in both groups maintained LDA (80% 4 mg; 67% 2 mg) or REM (40% 4 mg; 33% 2 mg) over 48 weeks. However, dose reduction resulted in small, statistically significant increases in disease activity at 12, 24 and 48 weeks. Dose reduction also produced earlier and more frequent relapse (loss of step-down criteria) over 48 weeks compared with 4 mg maintenance (23% 4 mg vs 37% 2 mg, p=0.001). Rescue rates were 10% for baricitinib 4 mg and 18% for baricitinib 2 mg. Dose reduction was associated with a numerically lower rate of non-serious infections (30.6 for baricitinib 4 mg vs 24.9 for 2 mg). Rates of serious adverse events and adverse events leading to discontinuation were similar across groups. Conclusions: In a large randomised, blinded phase 3 study, maintenance of RA control following induction of sustained LDA/REM with baricitinib 4 mg was greater with continued 4 mg than after taper to 2 mg. Nonetheless, most patients tapered to 2 mg could maintain LDA/REM or recapture with return to 4 mg if needed.

Original languageEnglish
JournalAnnals of the Rheumatic Diseases
DOIs
Publication statusAccepted/In press - 2018 Jan 1

Fingerprint

Disease control
Rheumatoid Arthritis
Prospective Studies
Maintenance
baricitinib
Safety
Recurrence
Infection

Keywords

  • disease activity
  • DMARDs (biologic)
  • DMARDs (synthetic)
  • rheumatoid arthritis

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Dose reduction of baricitinib in patients with rheumatoid arthritis achieving sustained disease control : Results of a prospective study. / Takeuchi, Tsutomu; Genovese, Mark C.; Haraoui, Boulos; Li, Zhanguo; Xie, Li; Klar, Rena; Pinto-Correia, Ana; Otawa, Susan; Lopez-Romero, Pedro; De La Torre, Inmaculada; Macias, William; Rooney, Terence P.; Smolen, Josef S.

In: Annals of the Rheumatic Diseases, 01.01.2018.

Research output: Contribution to journalArticle

Takeuchi, T, Genovese, MC, Haraoui, B, Li, Z, Xie, L, Klar, R, Pinto-Correia, A, Otawa, S, Lopez-Romero, P, De La Torre, I, Macias, W, Rooney, TP & Smolen, JS 2018, 'Dose reduction of baricitinib in patients with rheumatoid arthritis achieving sustained disease control: Results of a prospective study', Annals of the Rheumatic Diseases. https://doi.org/10.1136/annrheumdis-2018-213271
Takeuchi, Tsutomu ; Genovese, Mark C. ; Haraoui, Boulos ; Li, Zhanguo ; Xie, Li ; Klar, Rena ; Pinto-Correia, Ana ; Otawa, Susan ; Lopez-Romero, Pedro ; De La Torre, Inmaculada ; Macias, William ; Rooney, Terence P. ; Smolen, Josef S. / Dose reduction of baricitinib in patients with rheumatoid arthritis achieving sustained disease control : Results of a prospective study. In: Annals of the Rheumatic Diseases. 2018.
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abstract = "Objectives: This study investigated the effects of dose step-down in patients with rheumatoid arthritis (RA) who achieved sustained disease control with baricitinib 4 mg once a day. Methods: Patients who completed a baricitinib phase 3 study could enter a long-term extension (LTE). In the LTE, patients who received baricitinib 4 mg for ≥15 months and maintained CDAI low disease activity (LDA) or remission (REM) were blindly randomised to continue 4 mg or taper to 2 mg. Patients could rescue (to 4 mg) if needed. Efficacy and safety were assessed through 48 weeks. Results: Patients in both groups maintained LDA (80{\%} 4 mg; 67{\%} 2 mg) or REM (40{\%} 4 mg; 33{\%} 2 mg) over 48 weeks. However, dose reduction resulted in small, statistically significant increases in disease activity at 12, 24 and 48 weeks. Dose reduction also produced earlier and more frequent relapse (loss of step-down criteria) over 48 weeks compared with 4 mg maintenance (23{\%} 4 mg vs 37{\%} 2 mg, p=0.001). Rescue rates were 10{\%} for baricitinib 4 mg and 18{\%} for baricitinib 2 mg. Dose reduction was associated with a numerically lower rate of non-serious infections (30.6 for baricitinib 4 mg vs 24.9 for 2 mg). Rates of serious adverse events and adverse events leading to discontinuation were similar across groups. Conclusions: In a large randomised, blinded phase 3 study, maintenance of RA control following induction of sustained LDA/REM with baricitinib 4 mg was greater with continued 4 mg than after taper to 2 mg. Nonetheless, most patients tapered to 2 mg could maintain LDA/REM or recapture with return to 4 mg if needed.",
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AU - Li, Zhanguo

AU - Xie, Li

AU - Klar, Rena

AU - Pinto-Correia, Ana

AU - Otawa, Susan

AU - Lopez-Romero, Pedro

AU - De La Torre, Inmaculada

AU - Macias, William

AU - Rooney, Terence P.

AU - Smolen, Josef S.

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N2 - Objectives: This study investigated the effects of dose step-down in patients with rheumatoid arthritis (RA) who achieved sustained disease control with baricitinib 4 mg once a day. Methods: Patients who completed a baricitinib phase 3 study could enter a long-term extension (LTE). In the LTE, patients who received baricitinib 4 mg for ≥15 months and maintained CDAI low disease activity (LDA) or remission (REM) were blindly randomised to continue 4 mg or taper to 2 mg. Patients could rescue (to 4 mg) if needed. Efficacy and safety were assessed through 48 weeks. Results: Patients in both groups maintained LDA (80% 4 mg; 67% 2 mg) or REM (40% 4 mg; 33% 2 mg) over 48 weeks. However, dose reduction resulted in small, statistically significant increases in disease activity at 12, 24 and 48 weeks. Dose reduction also produced earlier and more frequent relapse (loss of step-down criteria) over 48 weeks compared with 4 mg maintenance (23% 4 mg vs 37% 2 mg, p=0.001). Rescue rates were 10% for baricitinib 4 mg and 18% for baricitinib 2 mg. Dose reduction was associated with a numerically lower rate of non-serious infections (30.6 for baricitinib 4 mg vs 24.9 for 2 mg). Rates of serious adverse events and adverse events leading to discontinuation were similar across groups. Conclusions: In a large randomised, blinded phase 3 study, maintenance of RA control following induction of sustained LDA/REM with baricitinib 4 mg was greater with continued 4 mg than after taper to 2 mg. Nonetheless, most patients tapered to 2 mg could maintain LDA/REM or recapture with return to 4 mg if needed.

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