On 2017 Mar 05, Andrea Messori commented:

Is baricitinib more effective than adalimumab?

by Andrea Messori (HTA unit, ESTAR, Firenze, Italy) and Daniele Mengato (Dept. of Pharmaceutical Sciences, University of Padova, Padova, Italy)

To increase the amount of clinical evidence supporting biosimilars, one report[1] has recently proposed to carry out a network meta-analysis (NETMA) that includes not only the equivalence study comparing the biosimilar with the originator, but also all randomized studies (RCTs) comparing the originator with the previous non-biologic standard of care; most of these RCTs were conducted over the interval between the registration of the originator and the registration of the biosimilar. This approach, originally aimed at biosimilars, can also be employed to better evaluate a newly developed biologic rather than a newly registrered biosimilar. In the case of a newly registered biosimilar, the objective is to establish if the equivalence between the biosimilar and the originator, already demonstrated in the registrative RCT, is also confirmed by the NETMA. In the case of a newly developed biologic, the objective is to establish if the superiority of the new biologic over the old one, already demonstrated in the pivotal RCT, is also confirmed by the NETMA.  

In patients with rhematoid arthritis, baricitinib (recently developed) has been shown to be more effective than adalimumab (end-point=ACR20; odds-ratio=1.44, 95% confidence interval: 1.06 to 1.95)[2]. We have reassessed this comparison using an "enhanced evidence" NETMA (bayesian approach, random-effect model, 60,000 iterations) in which 7 RCTs were included (Table 1). Our results (odds-ratio=1.44; 95% credible interval: 0.50 to 3.83) did not confirm the superiority of baricitinib over adalimumab.

References

[1] Messori A, Trippoli S, Marinai C. Network meta-analysis as a tool for improving the effectiveness assessment of biosimilars based on both direct and indirect evidence: application to infliximab in rheumatoid arthritis. Eur J Clin Pharmacol. 2016 Dec 14. [Epub ahead of print] PubMed PMID: 27966035.  

[2] Taylor PC, Keystone EC, van der Heijde D, et al. Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis. N Engl J Med. 2017;376:652-662.  

[3] 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;353:i1777.  

Table 1. Achievement of ACR20 in 7 randomized trials: the 6 trials comparing adalimumab+methotrexate vs methotrexate alone have been reported by Hazlewood et al.[3] while the 3-arm trial by Taylor et al.[2] has recently been published in the NEJM.

                 ACR20 at 24/26 weeks                                                                             Duration

STUDY                    BARICITINIB          METHOTREXATE        ADALIMUMAB<br>                              +METHOTREXATE   MONOTHERAPY        +METHOTREXATE

Kim HY et al.                   -                           40/65                          23/63                 24 weeks

ARMADA trial                  -                           45/67                           9/62                 24 weeks

HOPEFUL 1 study           -                        129/171                        92/163               26 weeks

Keystone EC et al.           -                        131/207                        59/200               24 weeks

Weinblatt ME et al.           -                          39/59                          23/61                 24 weeks

OPTIMA trial                    -                        207/466                      112/460                26 weeks

TAYLOR et al.             360/487                 219/330                      179/488                26 weeks

On 2017 Mar 05, Andrea Messori commented:

Is baricitinib more effective than adalimumab?

by Andrea Messori (HTA unit, ESTAR, Firenze, Italy) and Daniele Mengato (Dept. of Pharmaceutical Sciences, University of Padova, Padova, Italy)

To increase the amount of clinical evidence supporting biosimilars, one report[1] has recently proposed to carry out a network meta-analysis (NETMA) that includes not only the equivalence study comparing the biosimilar with the originator, but also all randomized studies (RCTs) comparing the originator with the previous non-biologic standard of care; most of these RCTs were conducted over the interval between the registration of the originator and the registration of the biosimilar. This approach, originally aimed at biosimilars, can also be employed to better evaluate a newly developed biologic rather than a newly registrered biosimilar. In the case of a newly registered biosimilar, the objective is to establish if the equivalence between the biosimilar and the originator, already demonstrated in the registrative RCT, is also confirmed by the NETMA. In the case of a newly developed biologic, the objective is to establish if the superiority of the new biologic over the old one, already demonstrated in the pivotal RCT, is also confirmed by the NETMA.  

In patients with rhematoid arthritis, baricitinib (recently developed) has been shown to be more effective than adalimumab (end-point=ACR20; odds-ratio=1.44, 95% confidence interval: 1.06 to 1.95)[2]. We have reassessed this comparison using an "enhanced evidence" NETMA (bayesian approach, random-effect model, 60,000 iterations) in which 7 RCTs were included (Table 1). Our results (odds-ratio=1.44; 95% credible interval: 0.50 to 3.83) did not confirm the superiority of baricitinib over adalimumab.

References

[1] Messori A, Trippoli S, Marinai C. Network meta-analysis as a tool for improving the effectiveness assessment of biosimilars based on both direct and indirect evidence: application to infliximab in rheumatoid arthritis. Eur J Clin Pharmacol. 2016 Dec 14. [Epub ahead of print] PubMed PMID: 27966035.  

[2] Taylor PC, Keystone EC, van der Heijde D, et al. Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis. N Engl J Med. 2017;376:652-662.  

[3] 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;353:i1777.  

Table 1. Achievement of ACR20 in 7 randomized trials: the 6 trials comparing adalimumab+methotrexate vs methotrexate alone have been reported by Hazlewood et al.[3] while the 3-arm trial by Taylor et al.[2] has recently been published in the NEJM.

                 ACR20 at 24/26 weeks                                                                             Duration

STUDY                    BARICITINIB          METHOTREXATE        ADALIMUMAB<br>                              +METHOTREXATE   MONOTHERAPY        +METHOTREXATE

Kim HY et al.                   -                           40/65                          23/63                 24 weeks

ARMADA trial                  -                           45/67                           9/62                 24 weeks

HOPEFUL 1 study           -                        129/171                        92/163               26 weeks

Keystone EC et al.           -                        131/207                        59/200               24 weeks

Weinblatt ME et al.           -                          39/59                          23/61                 24 weeks

OPTIMA trial                    -                        207/466                      112/460                26 weeks

TAYLOR et al.             360/487                 219/330                      179/488                26 weeks