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. 2019 Jun;22(6):1094-1106.
doi: 10.1111/1756-185X.13516. Epub 2019 Mar 22.

Efficacy and safety of tofacitinib for the treatment of rheumatoid arthritis in patients from the Asia-Pacific region: Post-hoc analyses of pooled clinical study data

Eun Bong Lee  1 , Hisashi Yamanaka  2 , Yi Liu  3 , Wen-Chan Tsai  4 , Connie Chen  5 , Kenneth Kwok  5 , Hyun-Jeong Yoo  6 , Lyndon J Llamado  7 , Lisy Wang  8 , Yingchun Luo  9 , Naonobu Sugiyama  10 , Yoshiya Tanaka  11
Affiliations

Efficacy and safety of tofacitinib for the treatment of rheumatoid arthritis in patients from the Asia-Pacific region: Post-hoc analyses of pooled clinical study data

Eun Bong Lee et al. Int J Rheum Dis. 2019 Jun.

Abstract

Aim: We report tofacitinib efficacy and safety in Asia-Pacific patients who participated in the rheumatoid arthritis (RA) clinical development program.

Method: This post-hoc analysis included pooled data from patients with RA in the Asia-Pacific region treated with tofacitinib with/without conventional synthetic disease-modifying antirheumatic drugs in Phase (P)1, 2, 3, and long-term extension (LTE) studies (one LTE ongoing; January 2016 data-cut). Efficacy was assessed over 24 months in patients who received tofacitinib 5 (N = 397) or 10 (N = 382) mg twice daily or placebo (N = 243) in three P2 and five P3 studies. Endpoints included American College of Rheumatology (ACR)20/50/70 responses, Disease Activity Score in 28 joints, erythrocyte sedimentation rate (DAS28-4[ESR]) and Clinical Disease Activity Index (CDAI) remission rates, and change from baseline in Health Assessment Questionnaire-Disability Index (∆HAQ-DI). Safety data pooled over 92 months from one P1, four P2, six P3, and two LTE studies for all tofacitinib doses (N = 1464) included incidence rates (IRs) (patients with events/100 patient-years) for adverse events (AEs) of special interest.

Results: At month 3, patients receiving tofacitinib 5/10 mg twice daily improved vs placebo in ACR20 (69.2%/77.9% vs 27.5%), ACR50 (36.9%/44.4% vs 9.5%), and ACR70 (15.1%/22.4% vs 2.7%) responses, remission rates for DAS28-4(ESR) (8.5%/18.5% vs 2.6%) and CDAI (6.1%/12.3% vs 0.5%), and ∆HAQ-DI (-0.5/-0.6 vs -0.1); improvements were sustained through 24 months. IRs (95% CI) were 9.4 (8.5, 10.3) for serious AEs, 9.1 (8.3, 10.1) for discontinuations due to AEs, 3.7 (3.2, 4.3) for serious infections, 5.9 (5.2, 6.7) for herpes zoster, and 0.8 (0.6, 1.1) for malignancies (excluding non-melanoma skin cancer).

Conclusion: In Asia-Pacific patients, tofacitinib improved signs/symptoms over 24 months. Safety over 92 months was generally consistent with global tofacitinib studies; however, infection IRs were higher in Asia-Pacific patients.

Keywords: clinical aspects; drug treatment; rheumatoid arthritis.

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Conflict of interest statement

EBL is a consultant for Pfizer Inc, and received a research grant from Green Cross Co, Republic of Korea. YL has nothing to disclose. W‐CT has received speaking or consultant fees from Abbott, AstraZeneca, Bristol‐Myers Squibb, Chugai, Janssen, Mitsubishi Tanabe, Pfizer Inc and Roche. HY has received research grants from AbbVie, Astellas, Ayumi, Bristol‐Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Kaken, Mitsubishi Tanabe, MSD, Nippon Shinyaku, Ono, Pfizer Inc, Takeda, Teijin, Torii and UCB; and has received lecturing or consulting fees from Astellas, Bristol‐Myers Squibb, Chugai, Daiichi Sankyo, Mitsubishi Tanabe, Nippon Kayaku, Pfizer Inc, Takeda, Teijin and YL Biologics. CC, KK, LJL, YL, NS, LW and H‐JY are employees and shareholders of Pfizer Inc. YT has received consulting and speaking fees from Astellas, Bristol‐Myers Squibb, Chugai, Daiichi Sankyo, Eli Lilly, Janssen, Mitsubishi Tanabe, Pfizer Inc, Sanofi, UCB and YL Biologics.

Figures

Figure 1
Figure 1
American College of Rheumatology (ACR) response rates through Month 24. (A) ACR20, (B) ACR50, and (C) ACR70 response rates through to month 24 by treatment sequence (P2/3 population). ACR20/50/70, 20%/50%/70% improvement in American College of Rheumatology criteria; BID, twice daily; P, Phase; SE, standard error. Full analysis set, no imputation. The P2/3 population included patients from three Phase 2 studies and five Phase 3 studies. Patients randomized to placebo advanced to tofacitinib at month 3 or month 6; beyond month 6 all patients were receiving tofacitinib 5 or 10 mg BID
Figure 2
Figure 2
Mean DAS28‐4(ESR) score and rates of DAS28‐4(ESR)‐defined and Clinical Disease Activity Index (CDAI)–defined remission and LDA through to month 24. (A) Mean DAS28‐4(ESR) score, (B) proportion of patients achieving DAS28‐4(ESR) remission (score ≤2.6), (C) proportion of patients achieving DAS28‐4(ESR) LDA (score ≤3.2), (D) proportion of patients achieving CDAI remission (score ≤2.8), and (E) proportion of patients achieving CDAI LDA (score ≤10) through to month 24 by treatment sequence (P2/3 population). BID, twice daily; CDAI, Clinical Disease Activity Index; DAS28‐4(ESR), Disease Activity Score in 28 joints, erythrocyte sedimentation rate; LDA, low disease activity; P, Phase; SE, standard error. Full analysis set, no imputation. The P2/3 population included patients from three Phase 2 studies and five Phase 3 studies. Patients randomized to placebo advanced to tofacitinib at month 3 or month 6; beyond month 6 all patients were receiving tofacitinib 5 mg or 10 mg BID
Figure 3
Figure 3
Mean HAQ‐DI score and mean change from baseline in HAQ‐DI score through to month 24. (A) Mean HAQ‐DI score and (B) mean change from baseline in HAQ‐DI score through to month 24 by treatment sequence (P2/3 population). BID, twice daily; HAQ‐DI, Health Assessment Questionnaire‐Disability Index; P, Phase; SE, standard error. Full analysis set, no imputation. The dotted line in panel B indicates the minimum clinically important difference for HAQ‐DI (improvement ≥0.22). The P2/3 population includes patients from three Phase 2 studies and five Phase 3 studies. Patients randomized to placebo advanced to tofacitinib at month 3 or month 6; beyond month 6 all patients were receiving tofacitinib 5 or 10 mg BID
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