Systematic Review and Network Meta-Analysis of Combination Treatments in Disease Modifying Anti-Rheumatic Drug Experienced Patients with Severe Rheumatoid Arthritis: Analysis of American College of Rheumatology Criteria Scores 20, 50, and 70: An Update

Michelle E. Orme¹, Charles Hawes² and Stephen A. Mitchell³, ¹ICERA consulting UK, Swindon, United Kingdom, ²Pfizer UK, Surrey, United Kingdom, ³Abacus International UK, Bicester, United Kingdom

Meeting: ACR/ARHP Annual Meeting 2015

Date of first publication: September 29, 2015

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

Session Information

Date: Monday, November 9, 2015

Title: Rheumatoid Arthritis - Small Molecules, Biologics and Gene Therapy Poster II

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: Biologic disease-modifying anti-rheumatic drugs (DMARDs) in combination with conventional DMARDs provide patients with severe rheumatoid arthritis (RA) and an inadequate response to conventional DMARDs with treatment options. A previously published systematic review/network meta-analysis (NMA)¹comparing the relative efficacy of biologic DMARDS was updated to take account of new clinical evidence for current and recently licensed treatments with alternative modes of administration, i.e. subcutaneous (SC) versus intravenous (IV).

Methods: The systematic review undertaken in April 2011 was updated in November 2014. Literature searches were conducted in MEDLINE, EMBASE and the Cochrane Library, in addition to hand searches of conference proceedings and reference lists. A Bayesian NMA, which estimates the relative effectiveness of treatments whilst preserving the randomized comparisons within each trial, was conducted in WinBUGS using a random-effects logit-link model fitted to the binomial trial data namely the count of patients reaching American College of Rheumatology (ACR) scores 20/50/70 at follow-up.

Results: In addition to the 13,647 citations originally identified¹, 7,328 citations were identified in the update, of which 18,337 were excluded after screening the title/abstract. After reviewing 2,638 full-text papers, 43 studies enrolling over 15,000 patients and reporting ACR outcomes between 12 and 30 weeks were identified for inclusion in the meta-analysis. The following nine biologic DMARDs/ conventional DMARD combinations were included in the evidence network: abatacept IV (5 randomized controlled trials (RCTs), n=1,484); abatacept SC (3 RCTs, n=1,113); adalimumab (8 RCTs, n=1,112); certolizumab pegol (4 RCTs, n=802); etanercept (8 RCTs, n=881); golimumab (4 RCTs, n=345); infliximab (7 RCTs, n=1,122); tocilizumab IV (8 RCTs, n=2,545); tocilizumab SC (1 RCT, n=631).

The table below presents the NMA results for ACR20/50/70 outcomes for combination treatments of interest.

TABLE
Treatment	Median OR vs. cDMARD (95% CrI)	% patients achieving ACR20/50/70 (95% CrI)
ACR20
Conventional DMARD	–	28.5% (25.0%, 32.4%)
Abatacept 10mg/kg/4 weeks IV + cDMARD	3.11 (2.06, 4.62)*	55.4% (44.2%, 65.7%)
Abatacept 125mg/week SC + cDMARD	3.50 (2.04, 6.23)*	58.3% (44.1%, 71.7%)
Adalimumab 40mg/2 weeks + cDMARD	3.22 (2.30, 4.53)*	56.3% (46.8%, 65.5%)
Certolizumab pegol 200mg/2 weeks + cDMARD	9.23 (5.78, 14.69)*	78.6% (69.2%, 85.9%)
Etanercept 2x25mg/week + cDMARD	9.39 (5.02, 17.98)*	79.0% (66.1%, 88.0%)
Golimumab 50mg/4 weeks + cDMARD	3.79 (2.35, 6.04)*	60.2% (47.7%, 71.4%)
Infliximab 3mg/kg/8 weeks + cDMARD	3.18 (2.23, 4.50)*	56.0% (46.2%, 65.3%)
Tocilizumab 162mg/week SC + cDMARD	4.18 (1.98, 9.22)*	62.5% (43.8%, 79.0%)
Tocilizumab 8mg/kg/4 weeks IV + cDMARD	4.63 (3.31, 6.64)*	64.9% (55.9%, 73.4%)
ACR50
Conventional DMARD	–	12.6% (10.3%, 15.2%)
Abatacept 10mg/kg/4 weeks IV + cDMARD	3.58 (2.23, 5.90)*	33.9% (23.3%, 47.0%)
Abatacept 125mg/week SC + cDMARD	3.86 (2.06, 7.37)*	35.7% (22.2%, 52.4%)
Adalimumab 40mg/2 weeks + cDMARD	3.71 (2.49, 5.57)*	34.8% (25.3%, 45.9%)
Certolizumab pegol 200mg/2 weeks + cDMARD	6.86 (3.97, 12.03)*	49.7% (35.3%, 64.3%)
Etanercept 2x25mg/week + cDMARD	11.24 (4.96, 26.87)*	61.7% (40.9%, 79.9%)
Golimumab 50mg/4 weeks + cDMARD	4.63 (2.41, 9.24)*	40.0% (24.9%, 57.8%)
Infliximab 3mg/kg/8 weeks + cDMARD	3.68 (2.42, 5.74)*	34.6% (24.8%, 46.4%)
Tocilizumab 162mg/week SC + cDMARD	5.27 (2.09, 13.43)*	43.0% (22.7%, 66.4%)
Tocilizumab 8mg/kg/4 weeks IV + cDMARD	5.47 (3.58, 8.50)*	44.1% (32.7%, 56.3%)
ACR70
Conventional DMARD	–	4.2% (3.1%, 5.7%)
Abatacept 10mg/kg/4 weeks IV+ cDMARD	3.65 (2.34, 6.13)*	13.8% (8.5%, 22.7%)
Abatacept 125mg/week SC + cDMARD	4.08 (2.36, 7.75)*	15.2% (8.7%, 26.7%)
Adalimumab 40mg/2 weeks + cDMARD	4.39 (2.84, 6.97)*	16.1% (10.1%, 25.2%)
Certolizumab pegol 200mg/2 weeks + cDMARD	13.66 (6.68, 33.64)*	37.4% (21.5%, 60.8%)
Etanercept 2x25mg/week + cDMARD	19.66 (5.31, 139.3)*	46.3% (18.2%, 86.3%)
Golimumab 50mg/4 weeks + cDMARD	5.51 (2.60, 12.65)*	19.5% (9.6%, 37.3%)
Infliximab 3mg/kg/8 weeks + cDMARD	3.63 (2.359, 5.88)*	13.7% (8.5%, 22.1%)
Tocilizumab 162mg/week SC + cDMARD	6.24 (2.63, 14.29)*	21.5% (9.9%, 39.8%)
Tocilizumab 8mg/kg/4 weeks IV + cDMARD	7.28 (4.53, 11.73)*	24.2% (15.2%, 36.4%)
Abbreviations: CrI, credible interval (Bayesian equivalent of a confidence interval); IV, intravenous; OR, odds ratio; SC, subcutaneous; *significant difference based on the 95% CrI

Conclusion: Based on the meta-analysis of the studies that met the inclusion criteria for this review, all biologic DMARDs in combination with conventional DMARDs were significantly more effective than conventional DMARDs alone in improving ACR 20/50/70 outcomes in patients with severe RA and an inadequate response to conventional DMARDs.

Etanercept in combination with conventional DMARDs was the most effective biologic DMARD combination in terms of ACR 20/50/70 response.

References: Orme ME et al. Systematic review and network meta-analysis of combination and monotherapy treatments in disease-modifying antirheumatic drug-experienced patients with rheumatoid arthritis: analysis of American College of Rheumatology criteria scores 20, 50, and 70. Biologics. 2012 (6): 429-64.

Disclosure: M. E. Orme, ICERA consulting, 5; C. Hawes, Pfizer Ltd, 3; S. A. Mitchell, Abacus International, 5.

To cite this abstract in AMA style:

Orme ME, Hawes C, Mitchell SA. Systematic Review and Network Meta-Analysis of Combination Treatments in Disease Modifying Anti-Rheumatic Drug Experienced Patients with Severe Rheumatoid Arthritis: Analysis of American College of Rheumatology Criteria Scores 20, 50, and 70: An Update [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/systematic-review-and-network-meta-analysis-of-combination-treatments-in-disease-modifying-anti-rheumatic-drug-experienced-patients-with-severe-rheumatoid-arthritis-analysis-of-american-college-of-rh/. Accessed .

ACR Meeting Abstracts - https://acrabstracts.org/abstract/systematic-review-and-network-meta-analysis-of-combination-treatments-in-disease-modifying-anti-rheumatic-drug-experienced-patients-with-severe-rheumatoid-arthritis-analysis-of-american-college-of-rh/