On 2016 Sep 08, Andrea Messori commented:

Active rheumatoid arthritis with inadequate response to methotrexate monotherapy: incremental benefit for infliximab plus methotrexate versus methotrexate alone

Andrea Messori, Sabrina Trippoli HTA Unit, ESTAR, Regional Health Service, Firenze, 50100 Italy

One strength of the meta-analysis by Hazlewood and co-workers [1] is that all pharmacological interventions aimed at rheumatoid arthritis have been evaluated in terms of efficacy. Since infliximab biosimilar has recently become available and its cost is lower than that of infliximab originator, evaluating the magnitude of the incremental benefit for infliximab plus methotrexate versus methotrexate alone is of interest.

In patients with active rheumatoid arthritis with inadequate response to methotrexate monotherapy, Hazlewood and co-workers [1] report a total of 5 randomised studies.

According to the end-point of ACR50 response at 30 weeks, the results found in these trials are shown in Table 1. The heterogeneity assessment (carried out according to Higgins and Thompson [2]) showed an I squared of 0% (with p=0.71).

If one analyses these data based on traditional pairwise meta-analysis (OMA software, Open Meta-Analyst, version 4.16.12, Tufts University, url http://tuftscaes.org/open_meta/), the pooled risk difference in favour of infliximab plus methotrexate vs methotrexate alone is +19.7% (95% confidence interval: +15.4% to +24.1%; fixed-effect model).

References

1. Hazlewood GS, Barnabe C, Tomlinson G, Marshall D, Devoe D, Bombardier C. Methotrexate monotherapy and methotrexate combination therapy with traditional and biologic disease modifying antirheumatic drugs for rheumatoid arthritis: abridged Cochrane systematic review and network meta-analysis. BMJ. 2016 Apr 21;353:i1777.

2. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002 Jun 15;21(11):1539-58.

Table 1. Data of ACR50 response reported in 5 randomized trials: comparison between Remicade plus methotrexate (R+MTX) vs methotrexate alone (MTX). Detailed references for the 5 trials are given in the Appendix.

ACR50 response

Abe 2006: R+MTX=15/49 (30.6%) vs MTX=4/47 (8.5%)

Lipsky et al 2000 (ATTRACT): R+MTX=18/86 (20.9%) vs MTX=7/88 (8.0%)

Mac Isaac 2014: R+MTX=6/30 (20.0%) vs MTX=0/31 (0.0%)

Westovens et al 2006 (START): R+MTX=110/360(30.6%) vs MTX=33/361 (9.1%)

Zhang 2006: R+MTX=38/87 (43.7%) vs MTX=22/86 (25.6%)

Overall crude rate R+MTX=187/612 (30.5%) vs MTX=66/613 (10.8%)

Appendix

-Abe T, Takeuchi T, Miyasaka N, et al. A multicenter, double-blind, randomized, placebo controlled trial of infliximab combined with low dose methotrexate in Japanese patients with rheumatoid arthritis. J Rheumatol 2006;33:37-44

-Lipsky PE, Van Der Heijde DMFM, St. Clair EW, et al. Infliximab and methotrexate in the treatment of rheumatoid arthritis. New Engl J Med 2000;343:1594-602

-Mac Isaac KD, Baumgartner R, Kang J, et al. Pre-treatment whole blood gene expression is associated with 14-week response assessed by dynamic contrast enhanced magnetic resonance imaging in infliximab-treated rheumatoid arthritis patients. PLoS ONE 2014;9 (12) (no pagination)

-Westhovens R, Yocum D, Han J, et al. The safety of infliximab, combined with background treatments, among patients with rheumatoid arthritis and various comorbidities: a large, randomized, placebo-controlled trial.[Erratum appears in Arthritis Rheum. 2007 May;56(5):1675 Note: Dosage error in article text]. Arthritis Rheum 2006;54:1075-86

-Zhang FC, Hou Y, Huang F, et al. Infliximab versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: A preliminary study from China. APLAR Journal of Rheumatology 2006;9:127-30

On 2016 Sep 08, Andrea Messori commented:

Active rheumatoid arthritis with inadequate response to methotrexate monotherapy: incremental benefit for infliximab plus methotrexate versus methotrexate alone

Andrea Messori, Sabrina Trippoli HTA Unit, ESTAR, Regional Health Service, Firenze, 50100 Italy

One strength of the meta-analysis by Hazlewood and co-workers [1] is that all pharmacological interventions aimed at rheumatoid arthritis have been evaluated in terms of efficacy. Since infliximab biosimilar has recently become available and its cost is lower than that of infliximab originator, evaluating the magnitude of the incremental benefit for infliximab plus methotrexate versus methotrexate alone is of interest.

In patients with active rheumatoid arthritis with inadequate response to methotrexate monotherapy, Hazlewood and co-workers [1] report a total of 5 randomised studies.

According to the end-point of ACR50 response at 30 weeks, the results found in these trials are shown in Table 1. The heterogeneity assessment (carried out according to Higgins and Thompson [2]) showed an I squared of 0% (with p=0.71).

If one analyses these data based on traditional pairwise meta-analysis (OMA software, Open Meta-Analyst, version 4.16.12, Tufts University, url http://tuftscaes.org/open_meta/), the pooled risk difference in favour of infliximab plus methotrexate vs methotrexate alone is +19.7% (95% confidence interval: +15.4% to +24.1%; fixed-effect model).

References

1. Hazlewood GS, Barnabe C, Tomlinson G, Marshall D, Devoe D, Bombardier C. Methotrexate monotherapy and methotrexate combination therapy with traditional and biologic disease modifying antirheumatic drugs for rheumatoid arthritis: abridged Cochrane systematic review and network meta-analysis. BMJ. 2016 Apr 21;353:i1777.

2. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002 Jun 15;21(11):1539-58.

Table 1. Data of ACR50 response reported in 5 randomized trials: comparison between Remicade plus methotrexate (R+MTX) vs methotrexate alone (MTX). Detailed references for the 5 trials are given in the Appendix.

ACR50 response

Abe 2006: R+MTX=15/49 (30.6%) vs MTX=4/47 (8.5%)

Lipsky et al 2000 (ATTRACT): R+MTX=18/86 (20.9%) vs MTX=7/88 (8.0%)

Mac Isaac 2014: R+MTX=6/30 (20.0%) vs MTX=0/31 (0.0%)

Westovens et al 2006 (START): R+MTX=110/360(30.6%) vs MTX=33/361 (9.1%)

Zhang 2006: R+MTX=38/87 (43.7%) vs MTX=22/86 (25.6%)

Overall crude rate R+MTX=187/612 (30.5%) vs MTX=66/613 (10.8%)

Appendix

-Abe T, Takeuchi T, Miyasaka N, et al. A multicenter, double-blind, randomized, placebo controlled trial of infliximab combined with low dose methotrexate in Japanese patients with rheumatoid arthritis. J Rheumatol 2006;33:37-44

-Lipsky PE, Van Der Heijde DMFM, St. Clair EW, et al. Infliximab and methotrexate in the treatment of rheumatoid arthritis. New Engl J Med 2000;343:1594-602

-Mac Isaac KD, Baumgartner R, Kang J, et al. Pre-treatment whole blood gene expression is associated with 14-week response assessed by dynamic contrast enhanced magnetic resonance imaging in infliximab-treated rheumatoid arthritis patients. PLoS ONE 2014;9 (12) (no pagination)

-Westhovens R, Yocum D, Han J, et al. The safety of infliximab, combined with background treatments, among patients with rheumatoid arthritis and various comorbidities: a large, randomized, placebo-controlled trial.[Erratum appears in Arthritis Rheum. 2007 May;56(5):1675 Note: Dosage error in article text]. Arthritis Rheum 2006;54:1075-86

-Zhang FC, Hou Y, Huang F, et al. Infliximab versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: A preliminary study from China. APLAR Journal of Rheumatology 2006;9:127-30