Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Tocilizumab Treatment in Patients with Rheumatoid Arthritis and an Inadequate Response to DMARDs and/or TNF Inhibitors: ACT-SURE Preliminary Results.

Bykerk7,  Vivian P., Alvaro-Gracia3,  Jose, Ivorra4,  Jose Andres Roman, Nurmohamed6,  Michael T., Pavelka5,  Karel, Bernasconi8,  Corrado, Stancati8,  Andrea

Addenbrookes Hospital, Cambridge, United Kingdom
Hautepierre Service de Rhumatologie, Strasbourg, France
Hospital Universitario de La Princesa, IIS Princesa, Madrid, Spain
Hospital Universitario Dr. Peset, Valencia, Spain
Institute of Rheumatology, Prague, Czech Republic
Jan van Breemen Institute, Amsterdam, The Netherlands
Mount Sinai Hospital, Toronto, ON, Canada
Roche, Basel, Switzerland

Background:

Safety and efficacy of TCZ have been demonstrated in 7 phase 3 controlled studies in pts with RA and DMARD-IR or TNFi-IR but not in pts who switched to TCZ without TNFi washout. The ACT-SURE study evaluated TCZ safety and efficacy in pts who were DMARD-IR or TNFi-IR, treated in tertiary academic and non academic centers as well as in private practice setting.

Methods:

ACT-SURE was a phase 3b, open-label, single-arm, 6-mo study of DMARD-IR/TNFi-IR pts with active RA treated with TCZ 8 mg/kg Q4W alone or in combination with DMARDs. Safety endpoints included adverse events (AEs) and serious AEs (SAEs). Efficacy endpoints included ACR and DAS28 responses. Analyses were stratified by prestudy TNFi use: TNFi-naive (DMARD-IR) pts, previous TNFi users (>2 mos since TNFi use) or recent TNFi users (<=2 mos since TNFi use). Subanalysis of pts who received TCZ monotherapy was also performed.

Results:

Of 1681 evaluable pts, 58% were DMARD-IR, 18% were previous TNFi users and 24% were recent TNFi users. Mean age of pts was 54 years; 81% were women. Mean RA duration was 8.2 years in DMARD-IR pts and 11.2/11.7 years in previous/recent TNFi users. Baseline DAS28 was similar among groups (5.9–6.2). Overall, 12.8% pts withdrew, 4.8% for safety-related reasons; infections were the primary safety-related cause of withdrawal (1.1% of pts or 1.8/100 patient-years [PY]). Rates/100 PY AEs/SAEs and serious infections were slightly lower in TNFi-naive pts than in those with previous TNFi exposure (Table). ALT shifts from normal at baseline to >3` ULN occurred in <3% of pts (Table). Onset of efficacy was rapid and increased over time: among the groups, DAS28 remission was achieved by 24%–38% of pts at wk 8 and 49%–62% of pts at wk 24. Clinical response tended to be higher in DMARD-IR pts, with little difference between recent and previous TNFi users (Table). At wk 24, mean DAS28 values were 2.34, 2.83 and 2.76 in DMARD-IR pts, previous TNFi users and recent TNFi users. Improvement in physical function was similar across groups: 74.1%, 71.1% and 70.2% of DMARD-IR pts, previous TNFi users and recent TNFi users achieved >=0.22 point change from baseline in HAQ-DI. In the subgroup of pts who received TCZ monotherapy, 66.9%, 43.5% and 23.8% achieved ACR20/50/70 response at wk 24; 49.8% achieved DAS28 remission.

Conclusions:

ACT-SURE was performed in a setting closer to clinical practice than is typical of phase 3 studies and confirmed the safety profile of TCZ shown in previous phase 3 trials. TCZ is effective when used in DMARD-IR pts as the first-line biologic and in TNFi-IR pts. TCZ was effective as monotherapy or with DMARDs. Efficacy was characterized by rapid onset of action and increasing response over time. These results did not show a difference in TCZ safety for pts who were previous or recent TNFi users, which supports treating pts with TCZ immediately after stopping TNFi use.

Table. Safety and Efficacy Outcomes at Wk 24

 AE Rate/100PYSAE Rate/100PYSerious Infections Rate/100PYInfusion Reactions % (n)aALT Shift From Baseline to >3×ULN % (n)
DMARD-IR551.118.64.26.8 (66)2.4 (23)
TNFi-IR, previous use654.428.77.67.4 (22)3.0 (9)
TNFi-IR, recent use652.618.06.06.1 (25)0.7 (3)
 ACR20 % (n)ACR50 % (n)ACR70 % (n)ACR90 % (n)DAS28 Remission % (n/n)
DMARD-IR70.5 (688)51.9 (507)31.8 (310)10.3 (101)61.6 (534/867)
TNFi-IR, previous use60.7 (181)35.2 (105)17.8 (53)6.4 (19)48.5 (117/241)
TNFi-IR, recent use62.7 (255)42.3 (172)19.7 (80)6.6 (27)50.4 (175/347)
n/n=no. pts who responded/no. evaluable pts.
aInfusion reaction=AE occurring during infusion of TCZ.

To cite this abstract, please use the following information:
Bykerk, Vivian P., Alvaro-Gracia, Jose, Ivorra, Jose Andres Roman, Nurmohamed, Michael T., Pavelka, Karel, Bernasconi, Corrado, et al; Tocilizumab Treatment in Patients with Rheumatoid Arthritis and an Inadequate Response to DMARDs and/or TNF Inhibitors: ACT-SURE Preliminary Results. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1840
DOI: 10.1002/art.29605

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