Session Information
Date: Monday, November 9, 2015
Title: Rheumatoid Arthritis - Small Molecules, Biologics and Gene Therapy Poster II
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: Treatment options delivering sustained efficacy when given as monotherapy in RA are limited.1 Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. Tofacitinib monotherapy demonstrated efficacy in adult patients (pts) with RA in two index studies (ORAL Solo2 and Start3). Open-label, long-term extension (LTE) studies enrolled pts to evaluate safety and efficacy of tofacitinib monotherapy and combination therapy. Here we present data up to Month (Mo) 84 for safety and Mo 60 for efficacy for pts who stayed on tofacitinib monotherapy in LTE studies.
Methods: Data were pooled from two tofacitinib LTE studies (NCT00413699 [ongoing; database unlocked as of Apr 2014 data cut-off] and NCT00661661). Pts from Phase (P) 1/2/3 tofacitinib index studies received tofacitinib 5 or 10 mg twice daily (BID) as monotherapy or with background csDMARD in LTE. For tofacitinib and permitted concomitant RA medications, dose adjustments were allowed for inadequate efficacy or safety reasons. In this analysis, pts were assigned to tofacitinib 5 or 10 mg BID groups based on average total daily dose in LTE (<15 mg/day or ≥15 mg/day, respectively). Monotherapy was defined as those pts who received tofacitinib without other DMARDs (except antimalarials) throughout the LTE. Baseline (BL) values were those of the index studies for pts enrolling in LTE within 14 days of index study; for all others, BL was start of LTE. Safety was evaluated up to Mo 84 and efficacy to Mo 60 due to limited sample size.
Results: 1808 pts initiated LTE on tofacitinib monotherapy; 1638 (91%) stayed on monotherapy throughout LTE (504 on 5 mg BID; 1134 on 10 mg BID). For pts staying on monotherapy, mean (max) treatment duration was 1157 (2522) and 788 (2104) days for 5 and 10 mg, respectively. Efficacy responses for tofacitinib monotherapy were stable up to Mo 60 (Table 1). In 5 and 10 mg groups, 68% and 88% of pts, respectively, stayed on initial dose throughout LTE. Proportion of pts staying on steroids decreased from 56% to 39% and 41% to 23%, respectively, from baseline to Mo 60. Rates of discontinuation due to lack of efficacy and adverse events (AE), and of serious infection and malignancies (excluding non-melanoma skin cancer) were low (Table 2).
Conclusion: In this analysis of pts receiving tofacitinib monotherapy in LTE studies, over 90% of pts stayed on monotherapy, most did not have tofacitinib dose adjustments or add a DMARD, and efficacy was sustained over 60 months, with low rates of discontinuations due to lack of efficacy or AEs.
References: 1. Smolen JS et al. Ann Rheum Dis 2014; 73: 492-509; 2. Fleischmann R et al. N Engl J Med 2012; 367: 495-507; 3. Lee EB et al. N Engl J Med 2014; 370: 2377-2386.
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Table 1: Efficacy responses over time in patients receiving tofacitinib monotherapy |
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Tofacitinib 5 mg BID |
Tofacitinib 10 mg BID |
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ACR20, % (N) |
ACR50, % (N) |
Change from baseline in DAS28-4(ESR) score, mean (N) |
Change from baseline in HAQ-DI score, mean (N) |
ACR20, % (N) |
ACR50, % (N) |
Change from baseline in DAS28-4(ESR) score, mean (N) |
Change from baseline in HAQ-DI score, mean (N) |
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Month 3 |
81.0 (483) |
58.6 (483) |
-2.7 (473) |
-0.64 (477) |
80.1 (1087) |
59.8 (1087) |
-2.9 (1067) |
-0.75 (1078) |
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Month 6 |
79.8 (470) |
58.1 (470) |
-2.7 (455) |
-0.63 (461) |
79.5 (1060) |
60.5 (1060) |
-2.9 (1043) |
-0.74 (1050) |
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Month 9 |
84.2 (450) |
61.8 (450) |
-2.8 (442) |
-0.65 (443) |
79.5 (1024) |
59.4 (1024) |
-2.9 (1008) |
-0.75 (1011) |
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Month 12 |
82.8 (436) |
62.6 (436) |
-2.8 (431) |
-0.66 (428) |
81.9 (986) |
61.4 (986) |
-3.0 (964) |
-0.75 (978) |
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Month 24 |
86.9 (365) |
69.0 (365) |
-2.9 (359) |
-0.67 (359) |
76.8 (529) |
58.4 (529) |
-2.9 (517) |
-0.67 (522) |
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Month 36 |
87.9 (331) |
66.8 (331) |
-2.9 (326) |
-0.64 (324) |
78.8 (392) |
57.9 (392) |
-3.0 (385) |
-0.65 (390) |
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Month 48 |
87.7 (187) |
67.4 (187) |
-3.1 (180) |
-0.67 (183) |
78.0 (141) |
52.5 (141) |
-3.0 (137) |
-0.65 (140) |
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Month 60 |
87.8 (115) |
69.6 (115) |
-3.0 (115) |
-0.64 (113) |
66.7 (24) |
25.0 (24) |
-2.5 (24) |
-0.54 (24) |
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ACR, American College of Rheumatology response; BID, twice daily; DAS28, disease activity score; HAQ-DI, Health Assessment Questionnaire-Disability Index; N, number of evaluable patients |
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Table 2: Summary of discontinuations, serious infections, and malignancies (excluding NMSC) in patients receiving tofacitinib monotherapy up to data cut-off |
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Tofacitinib 5 mg BID N=504 |
Tofacitinib 10 mg BID N=1134 |
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Tofacitinib exposure, patient-years |
1612 |
2476 |
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Discontinuations, n (%) |
217 (43.1) |
323 (28.5) |
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Due to lack of efficacy |
16 (3.2) |
16 (1.4) |
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Due to AEs |
108 (21.4) |
152 (13.4) |
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IR (95% CI) of discontinuations due to AEs |
7.1 (5.8, 8.5) |
6.2 (5.2, 7.2) |
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IR (95% CI) of serious infection |
2.9 (2.2, 3.9) |
2.4 (1.9, 3.1) |
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IR (95% CI) of malignancies (excluding NMSC) |
1.0 (0.6, 1.6) |
0.7 (0.4, 1.1) |
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AE, adverse event; BID, twice daily; CI, confidence interval; IR, incidence rate (patients with events per 100 patient-years); NMSC, non-melanoma skin cancer |
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To cite this abstract in AMA style:
Fleischmann R, Yazici Y, Wollenhaupt J, Wang L, Maniccia A, Kwok K, Takiya L, van Vollenhoven R. Clinical Outcomes for Rheumatoid Arthritis Patients Receiving Tofacitinib Monotherapy in the Open-Label Long-Term Extension over 6 Years [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/clinical-outcomes-for-rheumatoid-arthritis-patients-receiving-tofacitinib-monotherapy-in-the-open-label-long-term-extension-over-6-years/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/clinical-outcomes-for-rheumatoid-arthritis-patients-receiving-tofacitinib-monotherapy-in-the-open-label-long-term-extension-over-6-years/