Session Information
Session Title: Rheumatoid Arthritis - Small Molecules, Biologics and Gene Therapy: Safety of Biologics and Small Molecules in Rheumatoid Arthritis
Session Type: Abstract Submissions (ACR)
Background/Purpose: Tofacitinib has been approved in the US and other countries at the recommended dose 5 mg BID in patients (pts) with rheumatoid arthritis (RA) and an inadequate response (IR) to prior DMARDs. Several Phase 3 studies have been conducted as part of the tofacitinib clinical development program. Here we provide a comprehensive summary of efficacy and safety outcomes with the 5 mg BID dose from five DMARD-IR Phase 3 studies.
Methods: Week 12 efficacy and safety data for tofacitinib 5 mg BID and placebo (PBO) were compiled from five Phase 3 studies (NCT00814307, ORAL Solo; NCT00856544, ORAL Sync; NCT00853385, ORAL Standard; NCT00847613, ORAL Scan; and NCT00960440, ORAL Step). Pts with RA received tofacitinib as monotherapy (ORAL Solo) or with background DMARDs (ORAL Sync, ORAL Standard, ORAL Scan, ORAL Step). All pts in ORAL Standard and ORAL Scan had an IR to MTX, those in ORAL Step had an IR to TNFi, those in ORAL Solo were biologic or nonbiologic DMARD-IR, and those in ORAL Sync were nonbiologic DMARD-IR. Endpoints evaluated included ACR20, ACR50, ACR70 response rates, DAS remission (DAS28-4[ESR]<2.6), change in Health Assessment Questionnaire-Disability Index (HAQ-DI), adverse events (AEs), discontinuations due to AEs, serious adverse events (SAEs), and serious infection events (SIEs). For binary variables, such as ACR20/50/70 and DAS28-4(ESR)<2.6, non-responder imputation (NRI) was used.
Results: Baseline demographics and disease characteristics were generally similar within and between studies, except TNFi-IR pts having a longer history of RA than DMARD-IR. ACR20 rates were significantly improved with tofacitinib vs PBO either as monotherapy or with background DMARDs; ACR50 and ACR70 rates demonstrated similar patterns (Table 1). After only 12 weeks of treatment, significantly more pts receiving tofacitinib 5 mg BID than PBO achieved DAS28-4(ESR)<2.6, apart from those in ORAL Solo (Table 1). Significant changes from baseline in HAQ-DI were also observed with tofacitinib vs PBO, both as a monotherapy or with background DMARDs (Table 1).
Frequencies of AEs and SAEs were similar between tofacitinib and PBO across all studies (Table 1). Discontinuations due to AEs, by pts receiving tofacitinib, were ≤7% in all groups. Pooled and long-term analyses of Phase 3 and long-term extension studies have further described the AE profile associated with tofacitinib therapy.1
Conclusion: This comprehensive summary demonstrates that, regardless of prior therapy, short-term treatment with tofacitinib 5 mg BID significantly reduced signs and symptoms of RA, as measured by ACR20/50/70, DAS28-4(ESR)<2.6, and HAQ-DI. There were no unexpected safety findings at the US-recommended dose.
1. Wollenhaupt J et al. J Rheumatol 2014; 41: 837-52.
Disclosure:
P. Bird,
Abbvie,
8,
Pfizer Inc,
8,
Roche Pharmaceuticals,
8,
Celgene,
8,
Janssen Pharmaceutica Product, L.P.,
8,
UCB,
8;
W. Bensen,
Abbott Immunology Pharmaceuticals,
2,
Abbvie,
2,
Amgen,
2,
AstraZeneca,
2,
BMS,
2,
Janssen Pharmaceutica Product, L.P.,
2,
Merck Pharmaceuticals,
2,
Eli Lilly and Company,
2,
Novartis Pharmaceutical Corporation,
2,
Pfizer Inc,
2,
Proctor & Gamble Pharmaceuticals,
2,
Roche Pharmaceuticals,
2,
Sanofi-Aventis Pharmaceutical,
2,
Schering-Plough,
2,
Takeda,
2,
UCB,
2,
Warner Chilcott,
2,
Wyeth Pharmaceuticals,
2,
Abbott Immunology Pharmaceuticals,
5,
Abbvie,
5,
Amgen,
5,
AstraZeneca,
5,
BMS,
5,
Janssen Pharmaceutica Product, L.P.,
5,
Merck Pharmaceuticals,
5,
Eli Lilly and Company,
5,
Novartis Pharmaceutical Corporation,
5,
Pfizer Inc,
5,
Proctor & Gamble Pharmaceuticals,
5,
Proctor & Gamble Pharmaceuticals,
5,
Roche Pharmaceuticals,
5,
Sanofi-Aventis Pharmaceutical,
5,
Schering-Plough,
3,
Takeda,
5,
UCB,
5,
Warner,
5,
Warner Chilcott,
5,
Wyeth Pharmaceuticals,
5,
Abbott Immunology Pharmaceuticals,
8,
Abbvie,
8,
Amgen,
8,
AstraZeneca,
7,
BMS,
8,
Janssen Pharmaceutica Product, L.P.,
8,
Merck Pharmaceuticals,
8,
Eli Lilly and Company,
8,
Novartis Pharmaceutical Corporation,
8,
Pfizer Inc,
8,
Proctor & Gamble Pharmaceuticals,
8,
Roche Pharmaceuticals,
8,
Sanofi-Aventis Pharmaceutical,
8,
Takeda,
8,
UCB,
8,
Warner Chilcott,
8,
Wyeth Pharmaceuticals,
8;
B. El-Zorkany,
Abbott Immunology Pharmaceuticals,
5,
Abbvie,
5,
Amgen,
5,
BMS,
5,
Janssen Pharmaceutica Product, L.P.,
5,
Eli Lilly and Company,
5,
Merck Pharmaceuticals,
5,
Novartis Pharmaceutical Corporation,
5,
Pfizer Inc,
5,
Roche Pharmaceuticals,
5,
Sanofi-Aventis Pharmaceutical,
5,
Servier,
5,
UCB,
5,
Abbott Immunology Pharmaceuticals,
2,
Abbvie,
2,
Amgen,
2,
BMS,
2,
Janssen Pharmaceutica Product, L.P.,
2,
Eli Lilly and Company,
2,
Merck Pharmaceuticals,
2,
Novartis Pharmaceutical Corporation,
2,
Pfizer Inc,
2,
Roche Pharmaceuticals,
2,
Sanofi-Aventis Pharmaceutical,
2,
Servier,
2,
UCB,
2,
Abbott Immunology Pharmaceuticals,
8,
Abbvie,
8,
Amgem,
8,
BMS,
8,
Janssen Pharmaceutica Product, L.P.,
8,
Eli Lilly and Company,
8,
Merck Pharmaceuticals,
8,
Novartis Pharmaceutical Corporation,
8,
Pfizer Inc,
8,
Roche Pharmaceuticals,
8,
Sanofi-Aventis Pharmaceutical,
8,
Servier,
8,
UCB,
8;
J. Kaine,
Pfizer Inc,
8,
BMS,
8;
B. H. Manapat-Reyes,
Pfizer Inc,
8,
Amgen,
9;
V. Pascual-Ramos,
None;
D. Witcombe,
Pfizer Inc,
1,
Pfizer Inc,
3;
A. Anisfeld,
Pfizer Inc,
1,
Pfizer Inc,
3;
K. Soma,
Pfizer Inc,
1,
Pfizer Inc,
3;
R. Zhang,
Pfizer Inc,
1,
Pfizer Inc,
3;
K. Thirunavukkarasu,
Pfizer Inc,
1,
Pfizer Inc,
3.
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