RNA sequencing-based stratification of synovial tissue
Tocilizumab appears to be more effective than rituximab (which targets CD20 B cells) in patients classified as B-cell poor using RNA sequencing, but not in patients histologically classified as B-cell poor.[177]Humby F, Durez P, Buch MH, et al. Rituximab versus tocilizumab in anti-TNF inadequate responder patients with rheumatoid arthritis (R4RA): 16-week outcomes of a stratified, biopsy-driven, multicentre, open-label, phase 4 randomised controlled trial. Lancet. 2021 Jan 23;397(10271):305-17.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32341-2/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/33485455?tool=bestpractice.com
These results suggest that RNA sequencing-based stratification of rheumatoid arthritis (RA) synovial tissue is more strongly associated with clinical response than histopathological classification; further research is required before treatment recommendations can be made.
Olokizumab
Olokizumab, an investigational humanised monoclonal antibody targeting interleukin-6, in combination with methotrexate has been demonstrated to significantly improve the percentage of people with RA achieving ACR20/50/70, DSA28-CRP, CDAI and HAQ-DI response at 12 weeks compared with placebo.[178]Smolen JS, Feist E, Fatenejad S, et al. Olokizumab versus placebo or adalimumab in rheumatoid arthritis. N Engl J Med. 2022 Aug 25;387(8):715-26.
https://www.doi.org/10.1056/NEJMoa2201302
http://www.ncbi.nlm.nih.gov/pubmed/36001712?tool=bestpractice.com
[179]Abuelazm M, Ghanem A, Mahmoud A, et al. The efficacy and safety of olokizumab for rheumatoid arthritis: a systematic review, pairwise, and network meta-analysis. Clin Rheumatol. 2023 Jun;42(6):1503-20.
https://www.doi.org/10.1007/s10067-023-06519-6
http://www.ncbi.nlm.nih.gov/pubmed/36792848?tool=bestpractice.com
[180]Mahmoud AM. Olokizumab's effectiveness and safety in patients with rheumatoid arthritis: a systematic review and meta-analysis of randomized controlled trials. J Clin Densitom. 2023 Jan-Mar;26(1):61-82.
https://www.doi.org/10.1016/j.jocd.2022.12.003
http://www.ncbi.nlm.nih.gov/pubmed/36535857?tool=bestpractice.com
Treatment-related adverse effects were significantly higher in the olokizumab group compared with the placebo group, but serious treatment-related adverse effects did not differ significantly between the olokizumab group and the placebo group.[180]Mahmoud AM. Olokizumab's effectiveness and safety in patients with rheumatoid arthritis: a systematic review and meta-analysis of randomized controlled trials. J Clin Densitom. 2023 Jan-Mar;26(1):61-82.
https://www.doi.org/10.1016/j.jocd.2022.12.003
http://www.ncbi.nlm.nih.gov/pubmed/36535857?tool=bestpractice.com
Further large randomised controlled trials are needed to establish long term effects.[179]Abuelazm M, Ghanem A, Mahmoud A, et al. The efficacy and safety of olokizumab for rheumatoid arthritis: a systematic review, pairwise, and network meta-analysis. Clin Rheumatol. 2023 Jun;42(6):1503-20.
https://www.doi.org/10.1007/s10067-023-06519-6
http://www.ncbi.nlm.nih.gov/pubmed/36792848?tool=bestpractice.com
Peficitinib
Peficitinib, an investigational Janus kinase inhibitor, has been found to significantly increase the ACR20/50/70 response rate for people with RA compared with placebo using direct and indirect comparison meta-analysis.[181]Lee YH, Song GG. Comparative efficacy and safety of peficitinib 25, 50, 100, and 150 mg in patients with active rheumatoid arthritis: a bayesian network meta-analysis of randomized controlled trials. Clin Drug Investig. 2020 Jan;40(1):65-72.
https://www.doi.org/10.1007/s40261-019-00863-9
http://www.ncbi.nlm.nih.gov/pubmed/31602572?tool=bestpractice.com
An additional indirect comparison meta-analysis concluded that peficitinib is one of the most effective treatments for people with RA with an inadequate response to disease-modifying anti-rheumatic drugs (DMARDs).[182]Lee YH, Song GG. Comparison of the efficacy and safety of tofacitinib and peficitinib in patients with active rheumatoid arthritis: a bayesian network meta-analysis of randomized controlled trials. Int J Rheum Dis. 2020 Jul;23(7):868-75.
https://www.doi.org/10.1111/1756-185X.13854
http://www.ncbi.nlm.nih.gov/pubmed/32483919?tool=bestpractice.com
Results from one subsequent double blind phase 3 study suggests that peficitinib significantly increases the ACR20 response rate in Asian people with RA who have an inadequate response or intolerance to methotrexate compared with placebo.[183]Yang Y, Li J, Liu J, et al. Safety and efficacy of peficitinib in Asian patients with rheumatoid arthritis who had an inadequate response or intolerance to methotrexate: results of a multicenter, randomized, double-blind, placebo-controlled phase 3 study. Lancet Reg Health West Pac. 2024 Jan;42:100925.
https://www.doi.org/10.1016/j.lanwpc.2023.100925
http://www.ncbi.nlm.nih.gov/pubmed/38357391?tool=bestpractice.com