Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Tocilizumab Monotherapy and Tocilizumab Plus Disease-Modifying Antirheumatic Drugs in a US Rheumatoid Arthritis Population with Inadequate Response to Anti-Tumor Necrosis Factor Agents.
Weinblatt1, Michael E., Kremer2, Joel M., Cush3, John J., Rigby4, William, Teng5, Lichen, Singh5, Natasha, Malamet6, Raymond L.
Department of Medicine, Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA
Albany Medical College and The Center for Rheumatology, Albany, NY
Baylor Research Institute, Dallas, TX
Dartmouth Medical School, Lebanon, NH
Roche, Nutley, NJ
Genentech, South San Francisco, CA
Stanford University, Palo Alto, CA
ACT-STAR, a 24-wk, prospective, open-label, US study, demonstrated similar safety/tolerability/efficacy with tocilizumab (TCZ) monotherapy (MONO) or TCZ+DMARD combination (COMBO) in adult patients (pts) with moderate-to-severe active RA who had an inadequate response (IR) to current biologic or nonbiologic DMARDs. Efficacy of TCZ MONO was also previously demonstrated in a randomized trial of methotrexate-IR or naïve patients (AMBITION), but it is important to understand the risk-benefit profile of TCZ MONO specifically in the difficult-to-treat population of anti-TNF-IR pts. Therefore, a subanalysis of ACT-STAR was conducted to compare the safety/efficacy of TCZ MONO or COMBO therapy in anti-TNF-IR pts.
In ACT-STAR, pts on nonbiologic DMARDs alone or combined with biologic DMARDs were randomized to 2 TCZ COMBO groups (4 mg/kg [TCZ 4]+DMARD or 8 mg/kg [TCZ 8]+DMARD); pts on biologic DMARD monotherapy before baseline were assigned to TCZ 8 MONO. Biologic DMARDs were discontinued before baseline. At wk 8, pts randomized to TCZ 4+DMARD who did not achieve >=20% improvement in joint counts had TCZ dose increased to 8 mg/kg; from week 12 onward pts on TCZ 4+DMARD had dose increased at investigator's discretion. Pts on TCZ 8+DMARD could have TCZ dose decreased at any time for safety. We reviewed safety/efficacy results for pts who previously received anti-TNF agents. Primary outcome was number (%) of pts with serious adverse events (SAEs) and serious infection events (SIEs). Secondary variables included ACR20/50/70 and DAS28 scores.
The anti-TNF-IR subset in the intent-to-treat population comprised 552 pts (TCZ 4+DMARD=202; TCZ 8+DMARD=221; TCZ 8=129). Baseline disease characteristics in each group are shown in the table. Incidence rates of SAEs and SIEs were similar between COMBO groups and higher than those in the MONO group (Table). Most common SIEs were cellulitis and pneumonia; 2 pts in TCZ 4+DMARD group experienced GI perforations. Week 24 ACR response rates and DAS28 remission are also shown in the table for each treatment group (comparable to results for the overall population). At wk 24, pts in each group achieved a statistically significant change from baseline in DAS28 score (P<0.0001) (Table).
Table. Baseline Characteristics, Efficacy and Safety in the Anti-TNF-IR Subset of ACT-STAR
|Parameter||TCZ 4/8+DMARD||Treatment Group||TCZ 8 Monotherapy|
|n (intent-to-treat population, anti-TNF-IR)||202||221||129|
|RA disease duration (yrs), mean (SD)||12.7 (9.81)||12.0 (8.57)||13.2 (9.93)|
|DAS28 score, mean (SD)||5.78 (1.024)||5.65 (0.997)||6.13 (0.942)|
|Swollen joint count, mean (SD)||19.0 (11.53)||19.1 (10.62)||22.0 (12.00)|
|Tender joint count, mean (SD)||29.4 (14.30)||29.4 (15.70)||34.3 (16.26)|
|CRP (mg/dL), mean (SD)||1.70 (2.450)||1.43 (2.080)||1.85 (3.123)|
|Patients using >=2 previous anti-TNF agents,%||45.8%||54.6%||53.2%Efficacy (intent-to-treat population, anti-TNF-IR)|
|Week 24 ACR20 response,% of pts||43.1||48.9||47.3|
|Week 24 ACR50 response,% of pts||22.8||22.6||20.9|
|Week 24 ACR70 response,% of pts||6.9||8.1||5.4|
|Change from baseline in DAS28 score at week 24, mean (SD)||-1.76 (1.283)P<0.0001||-1.85 (1.373) P<0.0001||-1.95 (1.445)P<0.0001|
|DAS28 remission at week 24,% of pts||17.6||22.8||15.7|
|n (safety population, anti-TNF-IR)||203||240||109|
|AEs, Total Patients With >=1, n (%)||170 (83.7)||200 (83.3)||87 (79.8)|
|AEs causing discontinuationTotal Patients With >=1, n (%)Infections and infestationsGastrointestinal disordersSkin and subcutaneous tissue disorders||21 (10.3)6 (3.0)4 (2.0)4 (2.0)||10 (4.2)1 (0.4)1 (0.4)1 (0.4)||4 (3.7)1 (0.9)|
|SAEs, Total Patients With >=1, n (%)||15 (7.4)||19 (7.9)||5 (4.6)|
|Most common SAEs (>=1%), n (%)CellulitisPneumoniaCoronary Artery Disease||2 (1.0)3 (1.5)2 (1.0)||2 (0.8)3 (1.3)||2 (1.8)|
|SIEs, Total Patients With >=1, n (%)||9 (4.4)||9 (3.8)||2 (1.8)|
|Most common SIEs (>=1%), n (%)CellulitisPneumonia||2 (1.0)3 (1.5)||2 (0.8)3 (1.3)||2 (1.8)|
|Deaths, n (%)||1 (0.5)|||||
In this refractory, US population of pts failing at least 1 anti-TNF, SAE and SIE rates were comparable in COMBO groups, but higher than those in the MONO group. This subanalysis represents the first data assessing TCZ monotherapy specifically in anti-TNF-IR patients, demonstrating equivalent efficacy at the 8 mg/kg dose to TCZ+DMARD combination therapy and a positive risk-benefit profile. These results may have important implications for the use of TCZ monotherapy in the refractory population of patients who have failed therapy with an anti-TNF agent.
To cite this abstract, please use the following information:
Weinblatt, Michael E., Kremer, Joel M., Cush, John J., Rigby, William, Teng, Lichen, Singh, Natasha, et al; Tocilizumab Monotherapy and Tocilizumab Plus Disease-Modifying Antirheumatic Drugs in a US Rheumatoid Arthritis Population with Inadequate Response to Anti-Tumor Necrosis Factor Agents. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :427