Session Information
Date: Monday, November 6, 2017
Title: Rheumatoid Arthritis – Small Molecules, Biologics and Gene Therapy I: Outcomes Therapy
Session Type: ACR Concurrent Abstract Session
Session Time: 2:30PM-4:00PM
Background/Purpose: In patients (pts) with active RA and inadequate response (IR) to DMARDs, phase 3 studies demonstrated efficacy of baricitinib (2-mg and 4-mg). Larger, more rapid treatment effects were observed with baricitinib 4-mg. The objective of this study was to investigate the effects of baricitinib dose step-down in patients who achieved sustained disease control with baricitinib 4-mg.
Methods: Pts with RA who completed a baricitinib phase 3 study could enter a long-term extension (LTE) study. In the LTE, pts who received baricitinib 4-mg for ≥15 months and who achieved sustained low disease activity ([LDA] – CDAI score ≤10 for pts from RA-BUILD, RA-BEAM, RA-BEACON) or remission (CDAI ≤2.8 for DMARD-naïve pts from RA-BEGIN) at 2 consecutive visits ≥3 months apart were re-randomized in a blinded manner to either continue baricitinib 4-mg or step down to 2-mg. Pts could be rescued (to baricitinib 4-mg) if CDAI >10, or > 2.8 for pts from RA-BEGIN. Efficacy and safety were assessed through 48 weeks following re-randomization.
Results: The majority of pts in both groups maintained the state of LDA or remission over the 48-week period. However, dose reduction to 2-mg resulted in significant increases in disease activity at 12, 24, and 48 weeks. Dose reduction also resulted in a more rapid time to relapse (defined as loss of step-down eligibility criteria) with significantly more pts relapsing over 48 weeks compared to the 4-mg group. Rescue rates were 9.6% for baricitinib 4-mg, and 18.3% for baricitinib 2-mg. Most rescued pts could regain LDA or remission with the 4-mg dose. Dose reduction was associated with a numerically lower rate of non-serious infections; rates of serious adverse events and adverse events leading to discontinuation were similar across groups.
Conclusion: These data indicate disease control was better maintained on the 4-mg dose than 2-mg. Nonetheless, most stepped-down pts could maintain LDA or remission, or recapture control with return to the 4-mg dose if needed. Stepping down to a dose of 2-mg daily may be a reasonable consideration for some pts after having achieved sustained LDA or remission on the 4-mg dose.
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Patients originating from RA-BEAM, RA-BUILD, RA-BEACON Combined† |
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Week 12 |
Week 24 |
Week 48 |
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Continued bari 4-mg |
Stepped down to bari 2-mg |
Continued bari 4-mg |
Stepped down to bari 2-mg |
Continued bari 4-mg |
Stepped down to bari 2-mg |
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Efficacy measure |
NRI after rescue or for missing data |
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CDAI LDA ≤10 |
229/245 (93.5) |
203/245 (82.9)*** |
213/245 (86.9) |
183/245 (74.7)*** |
195/245 (79.6) |
164/245 (66.9)** |
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CDAI remission ≤2.8 |
101/245 (41.2) |
94/245 (38.4) |
108/245 (44.1) |
91/245 (37.1) |
99/245 (40.4) |
80/245 (32.7) |
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NRI only for missing data (observed data used after rescue) |
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CDAI LDA ≤10 |
229/245 (93.5) |
203/245 (82.9)*** |
218/245 (89.0) |
200/245 (81.6)* |
212/245 (86.5) |
196/245 (80.0) |
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CDAI remission ≤2.8 |
101/245 (41.2) |
94/245 (38.4) |
109/245 (44.5) |
96/245 (39.2) |
103/245 (42.0) |
90/245 (36.7) |
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Safety measure |
Weeks 0-48 |
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n [EAIR] |
Continued bari 4-mg N=245 |
Stepped down to bari 2-mg N=245 |
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SDEAE |
149 [67.4] |
128 [62.2] |
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Infection |
65 [29.4] |
54 [26.2] |
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SAE |
17 [7.7] |
15 [7.3] |
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Serious infection |
5 [2.3] |
4 [1.9] |
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AE ® discontinuation |
7 [3.2] |
7 [3.4] |
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Efficacy and safety data are n/N (%), and n [EAIR], respectively. †RA-BEAM=MTX-IR pts; RA-BUILD=csDMARD-IR pts; RA-BEACON=bDMARD-IR pts; AE=adverse event; bari=baricitinib; CDAI=Clinical Disease Activity Index; EAIR=exposure-adjusted incidence rate; LDA=low disease activity; n=number of responders; N=the number of patients re-randomized to the step down period at least 48 weeks prior to the data cut-off date (September 1, 2016); NRI=nonresponder imputation; SAE=serious adverse event; SDEAE=step-down emergent adverse event; *p≤0.05; **p≤0.01, ***p≤0.001 vs. continued bari 4-mg. |
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To cite this abstract in AMA style:
Takeuchi T, Genovese MC, Haraoui B, Li Z, Xie L, Klar R, Pinto Correia A, Otawa S, Lopez-Romero P, de la Torre I, Rooney TP, Smolen JS. Dose Reduction of Baricitinib in Patients with Rheumatoid Arthritis Achieving Sustained Disease Control: Results of a Prospective Study [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/dose-reduction-of-baricitinib-in-patients-with-rheumatoid-arthritis-achieving-sustained-disease-control-results-of-a-prospective-study/. Accessed .« Back to 2017 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/dose-reduction-of-baricitinib-in-patients-with-rheumatoid-arthritis-achieving-sustained-disease-control-results-of-a-prospective-study/