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A Quintet of Trials: Parts 1 & 2 TOWARD a New Future and a New OPTION in RA

A Quintet of Trials: Parts 1 & 2 TOWARD a New Future and a New OPTION in RA

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A Quintet of Trials: Parts 1 & 2 TOWARD a New Future and a New OPTION in RA

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  1. A Quintet of Trials: Parts 1 & 2TOWARD a New Future and a New OPTION in RA K PavelkaInstitute of Rheumatology and Clinic of Rheumatology, Charles University, Prague, Czech Republic

  2. The OPTION and TOWARD studies 1. Smolen JS, et al. Lancet 2008; 371:987997. 2. Genovese MC, et al. Arthritis Rheum 2008; 58:29682980.

  3. The OPTION and TOWARD studies International, randomised, double-blind, placebo-controlled, Phase III clinical trials in patients with moderate to severe RA of ≥6 months’ duration who had an inadequate response to prior DMARD therapy Patients unsuccessfully treated with an anti-TNF agent were excluded OPTION TCZ + MTX vs. placebo + MTX TOWARD TCZ + traditional DMARDs vs. placebo + traditional DMARDs 1. Smolen JS, et al. Lancet 2008; 371:987997. 2. Genovese MC, et al. Arthritis Rheum 2008; 58:29682980.

  4. Baseline disease characteristics were well balanced between treatment groups (ITT) Data shown as mean; pooled analysis of OPTION and TOWARD SJC=swollen joint countTJC=tender joint count HAQ=health assessment questionnaireCRP=C-reactive proteinESR=erythrocyte sedimentation rate Roche. Data on file.Genovese M et al. EULAR Congress 11-14 June 2008 Poster THU0185.

  5. OPTION and TOWARD: Study designs Screening Treatment period TCZ 8 mg/kg + MTX (n=205) Randomisation (n=623) OPTION TCZ 4 mg/kg + MTX (n=214) R 1:1:1 Placebo + MTX (n=204) TCZ 8 mg/kg + DMARDs (n=803) TOWARD Randomisation (n=1,220)* 2:1 R Placebo + DMARDs (n=413) Infusions Week 0 2 4 6 8 10 12 14 16 18 20 22 24 Rescue therapy *Two patients randomised to placebo + DMARDs and two patients randomised to TCZ 8 mg/kg + DMARDs were not dosed 1. Smolen JS, et al. Lancet 2008; 371:987997. 2. Genovese MC, et al. Arthritis Rheum 2008; 58:29682980.

  6. Pooled analysis The primary endpoint was the proportion of patients achieving ACR20 at Week 24 Patients from both studies who received TCZ 8 mg/kg or placebo (plus DMARDs/MTX) were included in the pooled analysis (ITT population) All subsequent data slides show data from the pooled analysis of OPTION and TOWARD 6

  7. OPTION: Patient disposition EnrolledN=623 Placebo + MTXn=204 TCZ 4 mg/kg + MTXn=214 TCZ 8 mg/kg + MTX n=205 12 withdrew 25 withdrew 13 withdrew Rescue therapyn=68 Rescue therapy n=31 Rescue therapy n=19 3 withdrew 3 withdrew 1 withdrew Completed 24 weeks191 (93%) Completed 24 weeks189 (93%) Completed 24 weeks186 (87%) Smolen JS, et al. Lancet 2008; 371:987997.

  8. TOWARD: Patient disposition EnrolledN=1,220 Placebo + DMARDsn=415 TCZ 8 mg/kg + DMARDsn=805 2 received no study medication 2 received no study medication 53 withdrew 43 withdrew Rescue therapy n=19 Rescue therapyn=45 Completed 24 weeksn=370 (89%) Completed 24 weeksn=751 (93%) Genovese MC, et al. Arthritis Rheum 2008; 58:29682980.

  9. Baseline demographics were well balanced between treatment groups (ITT) Data shown as mean except where indicated Genovese M et al. EULAR Congress 11-14 June 2008 Poster THU0185.

  10. Concomitant DMARDs at baseline (ITT) (TOWARD study*) * All patients were receiving MTX only at baseline in the OPTION study Smolen J et al.EULAR Congress 11-14 June 2008; Abstract: FRI0172.

  11. A significant improvement in ACR criteria was seen with TCZ treatment TCZ 8 mg/kg + DMARDs (n=1,008) Placebo + DMARDs (n=617) p<0.0001 p<0.0001 p<0.0001 70 60.3% 60 50 38.9% 40 Patients (%) 30 25.1% 20.8% 20 9.6% 10 2.6% 0 ACR20 ACR50 ACR70 Data shown for ACR responses at Week 24 Genovese M, et al. EULAR Congress 11-14 June 2008; Abstract THU0185.

  12. The ACR response to TCZ was rapid and sustained Placebo + DMARDs (n=617) TCZ 8 mg/kg + DMARDs (n=1,008) ACR20 ACR20 70 60 50 40 Patients (%) 30 20 10 0 0 4 8 12 16 20 24 Time (weeks) Beaulieu A, et al. EULAR Congress 11-14 June 2008; Abstract THU0184.

  13. The ACR response to TCZ was rapid and sustained Placebo + DMARDs (n=617) TCZ 8 mg/kg + DMARDs (n=1,008) ACR20 ACR20 ACR50 ACR50 70 60 50 40 Patients (%) 30 20 10 0 0 4 8 12 16 20 24 Time (weeks) Beaulieu A, et al. EULAR Congress 11-14 June 2008; Abstract THU0184.

  14. The ACR response to TCZ was rapid and sustained Placebo + DMARDs (n=617) TCZ 8 mg/kg + DMARDs (n=1,008) ACR20 ACR20 ACR50 ACR50 ACR70 ACR70 70 60 50 40 Patients (%) 30 20 10 0 0 4 8 12 16 20 24 Time (weeks) Beaulieu A, et al. EULAR Congress 11-14 June 2008; Abstract THU0184.

  15. DAS28 scores improved rapidly with TCZ treatment TCZ 8 mg/kg + DMARDs (n=1,008) Placebo + DMARDs (n=617) 7 6 ∆ = –1.25 5 Mean DAS28 4 ∆ = –3.18 3 4 8 12 16 20 24 0 Time (weeks) Roche. Data on file.

  16. Significantly more patients were in DAS28 remission (DAS28 <2.6) at Week 24 with TCZ p<0.0001 35 29.7% 30 25 20 Patients (%) 15 10 5 2.7% 0 Placebo + DMARDs (n=617) TCZ 8 mg/kg + DMARDs (n=1,008) Smolen J et al.EULAR Congress 11-14 June, 2008; Abstract: FRI0172.

  17. More patients had a clinical response by EULAR response criteria at Week 24 with TCZ Patients with a good/moderate response 79.7% 80 70 60 50 40 36.6% Patients (%) 30 20 10 0 Placebo + DMARDs (n=617) TCZ 8 mg/kg + DMARDs (n=1,008) Smolen J et al.EULAR Congress 11-14 June, 2008; Abstract: FRI0172.

  18. EULAR response was rapid and sustained with TCZ TCZ 8 mg/kg + DMARDs (n=1,008) Placebo + DMARDs (n=617) Patients with a good/moderate response 90 80 79.7% 70 60 Patients (%) 50 40 36.6% 30 20 10 0 0 4 8 12 16 20 24 Time (weeks) Roche. Data on file.

  19. TCZ induced rapid and sustained normalisation of CRP levels TCZ 8 mg/kg + DMARDs (n=1,008) Placebo + DMARDs (n=617) 3.0 2.5 2.0 ∆ = –0.387 Mean CRP levels (mg/dl) 1.5 1.0 ULN ∆ = –2.337 0.5 0.0 0 4 8 12 16 20 24 Time (weeks) ULN=upper limit of normal Genovese M, et al. EULAR Congress 11-14 June 2008; Abstract THU0185.

  20. TCZ has the potential to reverse chronic anaemia TCZ treatment increased levels of haemoglobin compared with DMARD therapy alone Greatest improvement in patients with baseline haemoglobin level <LLN Placebo + DMARDs (n=132*) TCZ 8 mg/kg + DMARDs (n=208*) 16 15 14 Haemoglobin level (g/dl) 13 ∆ = 1.6029 12 11 0 4 8 12 16 20 24 Time (weeks) * Patients with haemoglobin <LLN at baselineLLN=lower limit of normal Smolen J et al.EULAR Congress 11-14 June, 2008; Abstract: THU0168.

  21. FACIT-Fatigue scores at Week 24 were significantly improved with TCZ p<0.0001 10.0 8.04 7.5 Mean change from baseline in FACIT-Fatigue score MCID=5.0 5.0 3.69 2.5 0 Placebo + DMARDs (n=617) TCZ 8 mg/kg + DMARDs (n=1,008) MCID=minimal clinically important difference Roche. Data on file.

  22. Disability was significantly improved at Week 24 for TCZ-treated patients p<0.0001 80 67.9% 60 49.9% Patients with an improvement in HAQ-DI score ≥0.25 at Week 24 (%) 40 20 0 Placebo + DMARDs (n=617) TCZ 8 mg/kg + DMARDs (n=1,008) HAQ–DI=health assessment questionnaire–disability index Smolen J et al.EULAR Congress 11-14 June 2008; Abstract AB0353.

  23. Improvements were seen in SF-36 summary scores at Week 24 with TCZ TCZ 8 mg/kg + DMARDs (n=1,008) Placebo + DMARDs (n=617) 12 p<0.0001 p<0.0001 10 9.2 8 6.4 Change from baseline in SF-36 scores at Week 24 6 4.7 4 MCID=2.5–5.01–3 3.0 2 0 Physical component score Mental component score Alten R et al.EULAR Congress 11-14 June, 2008; Abstract: AB0345.1. Lubeck DP, Pharmacoeconomics 2004;22:27–38.2. Samsa G, et al. Pharmacoeconomics 1999;15:141–55. 3. Kosinski M, et al. Arthritis Rheum 2000;43(7):1478–1487. MCID=Minimal clinically important difference

  24. The toxicity profile of TCZ + DMARDs vs. placebo + DMARDs was comparable Pooled safety data will be presented in subsequent sessions AE=adverse event Smolen J et al.EULAR Congress 11-14 June 2008; Abstract FRI0163.

  25. Serious infections were uncommon Pooled safety data will be presented in subsequent sessions Smolen J et al.EULAR Congress 11-14 June 2008; Abstract FRI0163.

  26. TOWARD a New Future and a New OPTION in RA: Summary ACTEMRA 8 mg/kg + DMARDs compared with placebo + DMARDs resulted in: Higher proportion of patients achieving ACR20, ACR50, ACR70 and good/moderate EULAR responses Higher mean reduction in DAS28 Higher DAS28 remission rates Rapid reduction in clinical and laboratory variables of inflammation with normalisation of CRP and haemoglobin levels ACTEMRA 8 mg/kg + DMARDs was well tolerated in patients who had an inadequate response to prior DMARD therapy

  27. TOWARD a new future and a new OPTION in RA: Conclusions ACTEMRA: Significantly decreased disease activity and this improvement was sustained over 24 weeks Improved fatigue and reduced inflammation, as demonstrated by rapid and sustained normalisation of CRP levels Normalised haemoglobin levels in RA patients with chronic anaemia Led to rapid, sustained and clinically relevant improvement in patient quality of life, as demonstrated by improvements in HAQ-DI and SF-36 scores