2247 - Systematic Review and Network Meta-Analysis of Combination Therapy for Methotrexate-Experienced, Rheumatoid Arthritis Patients: Analysis of American College of Rheumatology Criteria Scores 20, 50 and 70

Tuesday, November 8, 2011: 9:00 AM-6:00 PM
Hall F2 - Poster Hall (McCormick Place West)
Michelle E. Orme1, Iain Fotheringham2, Stephen A. Mitchell2, Dean Spurden3 and Alex Bird3, 1ICERA consutling, United Kingdom, 2Abacus International, United Kingdom, 3Pfizer Ltd, Surrey, United Kingdom
Presentation Number: 2247

Background/Purpose: To determine the relative effectiveness of all UK licensed biological disease-modifying anti-rheumatic drugs (bDMARDs) for the treatment of rheumatoid arthritis (RA), in particular the concomitant use of bDMARDs with methotrexate (MTX) after failure of one or more DMARD.

Method: A comprehensive systematic review was conducted to identify randomised controlled trials of bDMARDS for the treatment of RA in MTX experienced patients (defined as patients with an inadequate response to at least 1 cycle of MTX (6 months) or withdrawn from MTX due to adverse events). This analysis covers combination therapy (biological DMARD + other DMARD) in MTX experienced patients and:

  • Excludes studies in MTX naïve patients
  • Excludes study arms evaluating biologic monotherapy, except if this results in only one remaining study arm for the meta-analysis (the biologic monotherapy arm is then included as the control for this study).
  • MTX monotherapy controls are included in the network and MTX is the reference treatment for the network meta-analysis (NMA).

Structured literature searches were conducted in MEDLINE, EMBASE, and the Cochrane Library, as well as hand searches of conference proceedings and reference lists.  From this 13,649 citations were identified, of which 12,984 were excluded based on the title/abstract. After reviewing 665 full-text papers, there were 26 eligible studies that reported endpoints based on ACR criteria reported between 12 and 30 weeks.

A network meta-analysis was conducted to estimate the relative effectiveness of treatments whilst preserving the randomised comparisons within each trial. A Bayesian network meta-analysis was conducted using a random-effects, logit model fitted to the binomial ACR20/50/70 trial data and was coded in WinBUGS. Direct probability statements are based on results from two chains of 20,000 samples.

Result: The table below summarise the network meta-analysis results for ACR 20/50/70.

Treatment

Log-OR vs MTX

(95% CrI)

% pts achieving ACR20/50/70 (95% CrI)

Probability best

ACR70

Etanercept 2x25mg/week + MTX

3.34 (1.11, 6.55)*

55.3% (12.8%, 97.3%)

62.59%

Certolizumab Pegol 200mg/2 weeks + MTX

2.61 (1.38, 3.96)*

41.4% (15.8%, 73.8%)

27.17%

Tocilizumab 8mg/kg/month + MTX

1.93 (0.76, 3.1)*

27.3% (9.2%, 54.5%)

5.2%

Golimumab 50mg/month + MTX

1.64 (0.26, 3.03)*

22.9% (5.8%, 52.6%)

3.48%

Abatacept 10mg/kg/month + MTX

1.49 (0.62, 2.41)*

19.3% (7.9%, 37.8%)

0.57%

Rituximab 2x1000mg + MTX

1.1 (-0.13, 2.39)

14.9% (4%, 36.9%)

0.51%

Adalimumab 40mg/2 weeks + MTX

1.34 (0.51, 2.19)*

17.1% (7%, 33.1%)

0.25%

Infliximab 3mg/kg/2 months + MTX

1.3 (0.49, 2.21)*

16.7% (6.9%, 33.2%)

0.24%

MTX

-

4.9% (3.2%, 7.1%)

0%

ACR50

Etanercept 2x25mg/week + MTX

3.04 (1.65, 4.65)*

71.8% (40.9%, 93.6%)

77.79%

Certolizumab Pegol 200mg/2 weeks + MTX

2.29 (1.41, 3.22)*

57.1% (34.6%, 78.1%)

17.54%

Golimumab 50mg/month + MTX

1.65 (0.67, 2.63)*

42.1% (20.3%, 66.8%)

2.21%

Tocilizumab 8mg/kg/month + MTX

1.55 (0.65, 2.45)*

39.8% (19.9%, 62.6%)

1.27%

Rituximab 2x1000mg + MTX

1.42 (0.49, 2.38)*

37% (17.6%, 60.8%)

0.89%

Adalimumab 40mg/2 weeks + MTX

1.4 (0.77, 2.05)*

36.1% (21.5%, 53.2%)

0.15%

Infliximab 3mg/kg/2 months + MTX

1.34 (0.73, 1.97)*

34.8% (20.8%, 51.4%)

0.09%

Abatacept 10mg/kg/month + MTX

1.3 (0.65, 1.96)*

33.8% (19.5%, 51%)

0.08%

MTX

-

12.1% (9%, 15.9%)

0%

ACR20

Etanercept 2x25mg/week + MTX

2.35 (1.34, 3.41)*

80.1% (60.6%, 92.8%)

44.94%

Certolizumab Pegol 200mg/2 weeks + MTX

2.42 (1.7, 3.16)*

81.7% (68.2%, 91.2%)

52.89%

Tocilizumab 8mg/kg/month + MTX

1.43 (0.68, 2.19)*

63% (43.9%, 79.7%)

0.89%

Golimumab 50mg/month + MTX

1.21 (0.38, 2.04)*

58% (36.7%, 77.1%)

0.45%

Abatacept 10mg/kg/month + MTX

1.16 (0.61, 1.71)*

56.9% (41.6%, 71.3%)

0.05%

Rituximab 2x1000mg + MTX

1.33 (0.56, 2.11)*

60.7% (40.8%, 78.4%)

0.61%

Adalimumab 40mg/2 weeks + MTX

1.26 (0.71, 1.81)*

59.3% (44.3%, 73.2%)

0.1%

Infliximab 3mg/kg/2 months + MTX

1.32 (0.81, 1.84)*

60.8% (46.5%, 73.9%)

0.08%

MTX

-

29.6% (23.7%, 36%)

0%

 Abbreviations: CrI, credible interval (Bayesian probability interval); * p<0.05

Conclusion: In conclusion, in these selected studies, concomitant bDMARDs were significantly more effective than MTX alone in improving ACR 20/50/70 outcomes in MTX experienced patients. Out of the studies that met inclusion in our analysis, Etanercept had the highest probability of being the most effective concomitant bDMARD for achieving ACR 70 and 50 responses, whilst certolizumab pegol had the highest probability of achieving ACR 20 response.


Keywords: DMARDs, meta-analysis and rheumatoid arthritis (RA)

Disclosure: M. E. Orme, Consultant to Pfizer Ltd, 5 ; I. Fotheringham, Consultant to Pfizer Ltd, 5 ; S. A. Mitchell, Consultant to Pfizer Ltd, 5 ; D. Spurden, Paid employee of Pfizer Ltd, 3 ; A. Bird, Paid employee of Pfizer Ltd, 3 .