Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: Fostamatinib (Fosta) is an oral SYK inhibitor. This 24-wk study (NCT01197755) compared Fosta vs placebo (PBO) on methotrexate (MTX) treatment in patients (pts) with active RA and an inadequate response to a single TNF-α antagonist.
Methods: Adult pts on MTX were randomized (1:1:1) to Fosta (100 mg bid for 24 wks [n = 105; Group (Gp) A] or 100 mg bid for 4 wks then 150 mg qd [n = 108; Gp B]) or to PBO (n = 109; Gp C) for 24 wks. Non-responders at Wk 12 could leave the study and enter an active extension study. The primary endpoint was the proportion of pts achieving ACR20 response at Wk 24. Secondary endpoints evaluated efficacy, safety and tolerability up to 24 wks.
Results: Baseline characteristics were well balanced across gps. Fosta Gp A, but not Gp B had significantly more pts achieving ACR20 at Wk 24 vs PBO (Table, p=0.004; p=0.168 respectively). At Wk 24, 36.2% of pts in Gp A, 27.8% of pts in Gp B, and 21.1% of pts on PBO achieved ACR20 (Table). Improvement was seen as early as Wk 1 (Table). Secondary endpoints were not tested statistically for Gp B due to failure of the primary endpoint. Fosta Gp A did not show a difference in radiographic outcomes at Wk 24 vs PBO. Frequently reported adverse events (AEs) in Gps A, B and PBO were diarrhea (20.0%, 26.9%, 6.4%), hypertension (13.3%, 13.9%, 8.3%) and headache (7.6%, 8.3%, 10.1%). Serious AEs occurred in 6.7%, 6.5% and 5.5% of pts. AEs leading to discontinuation (DAE) occurred in 9.5%, 10.2% and 8.3% of pts, the most frequent being diarrhea, abdominal pain, and vomiting. Elevated BP (≥ 140/90 mmHg) was observed in 46.7%, 51.9%, and 26.6% of pts at ≥ 1 visit.
The majority of pts’ hypertension could be managed per protocol. 30/187 pts without baseline hypertension started antihypertensives during the study (10, 15, and 5 in Gps A, B and C, respectively). In pts on baseline antihypertensives, 50/135 pts had an increase in baseline medication and/or a new therapy (21, 18, and 11 in Gps A, B and C, respectively). Three pts (2 Gp A; and 1 in Gp B) had a DAE due to hypertension.
There were 3 adjudicated CV events in Fosta Gp B (cardiopulmonary arrest with fatal myocardial infarction [2.4/100 PY]; heart failure; syncope). One event in PBO was adjudicated as indeterminate (2.7/100 PY; sudden death, unknown etiology). These were the only two deaths in the trial. There was 1 malignancy (2.4/100 PY; renal cell carcinoma) in Fosta Gp B.
Conclusion: In this phase III study in pts with an inadequate response to a single TNF-α antagonist, Fosta 100 mg bid but not Fosta 100 mg bid for 4 wks then 150 mg qd achieved statistical improvements in ACR20 response rate at 24 wks vs PBO. The overall level of response was not as large as had been anticipated based on evaluation of Phase 2 results (eg the TASKi program). Safety and tolerability findings were consistent with the profile observed in earlier Fosta studies.
Disclosure:
M. Genovese,
Rigel Pharma,
2,
Rigel Pharma,
5,
AstraZeneca,
2,
AstraZeneca,
5;
D. van der Heijde,
AbbVie,
5,
Amgen,
5,
AstraZeneca,
5,
Augurex,
5,
Bristol-Myers Squibb,
5,
Celgene,
5,
Centocor, Inc.,
5,
Chugai,
5,
Covagen,
5,
Daiichi Pharmaceutical Corporation,
5,
Eli Lilly and Company,
5,
GlaxoSmithKline,
5,
Janssen Biologics,
5,
Merck Pharmaceuticals,
5,
Novartis Pharmaceutical Corporation,
5,
Novo-Nordisk,
5,
Otsuka,
5,
Pfizer Inc,
5,
Roche Pharmaceuticals,
5,
Sanofi-Aventis Pharmaceutical,
5,
Schering-Plough,
5,
UCB,
5,
Vertex,
5,
Imaging Rheumatology BV,
9;
E. Keystone,
AstraZeneca,
2,
Abbott Laboratories,
2,
Amgen,
2,
Baylis Medical,
2,
Bristol-Myers Squibb,
2,
Hoffmann-La Roche, Inc.,
2,
Janssen Pharmaceutica Product, L.P.,
2,
Lilly Pharmaceuticals,
2,
Novartis Pharmaceutical Corporation,
2,
Pfizer Inc,
2,
Sanofi-Aventis Pharmaceutical,
2,
UCB,
2,
Abbott Laboratories,
5,
AstraZeneca,
5,
Biotest,
5,
Bristol-Myers Squibb,
5,
Hoffmann-La Roche, Inc.,
5,
Genentech and Biogen IDEC Inc.,
5,
Jannsen Inc,,
5,
Lilly Pharmaceuticals,
5,
Merck Pharmaceuticals,
5,
Nycomed,
5,
Pfizer Inc,
5,
UCB,
5,
Abbott Laboratories,
8,
AstraZeneca,
8,
Bristol-Myers Squibb,
8,
Hoffmann-La Roche, Inc.,
8,
Janssen Inc,
8,
Pfizer Inc,
8,
UCB,
8,
Amgen,
8;
A. Spindler,
AstraZeneca,
9;
C. L. Benhamou,
Servier,
2,
Amgen,
2,
Rotta Pharmaceuticals Inc.,
5,
Novartis Pharmaceutical Corporation,
6,
Roche Pharmaceuticals,
6;
A. Kavanaugh,
None;
E. Fudman,
AstraZeneca,
2,
Astellas,
2,
Bristol-Myers Squibb,
2,
Genentech and Biogen IDEC Inc.,
2,
Pfizer Inc,
2,
Sanofi-Aventis Pharmaceutical,
2;
K. Lampl,
AstraZeneca,
1,
AstraZeneca,
3;
C. O’Brien,
AstraZeneca,
1,
AstraZeneca,
3;
E. Duffield,
AstraZeneca,
3;
J. Poiley,
AstraZeneca,
2;
M. Weinblatt,
Rigel Pharma,
5,
AstraZeneca,
5.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/oskira-3-a-phase-iii-multicenter-randomized-double-blind-placebo-controlled-parallel-group-study-of-2-dosing-regimens-of-fostamatinib-in-rheumatoid-arthritis-patients-with-an-inadequate-response/