Rheumatoid arthritis - Emerging treatments

Filgotinib

Filgotinib, an investigational oral selective Janus kinase-1 selective (JAK1) inhibitor, is approved in Europe and the UK for the treatment of moderate-to-severe active rheumatoid arthritis in adults who have responded inadequately to, or who are intolerant to, one or more disease-modifying antirheumatic drugs (DMARDs). It may be used as monotherapy or in combination with methotrexate. One systematic review demonstrated that filgotinib is significantly more effective in achieving ACR20/50/70 responses at 12 and 24 weeks in people with rheumatoid arthritis (RA) with no significant difference in adverse effects.[179] The National Institute for Health and Care Excellence (NICE) in the UK recommends filgotinib in combination with methotrexate as an option for treating adults with moderate to severely active RA (a disease activity score [DAS28] of 3.2 or more), who have an inadequate response to intensive therapy with two or more conventional DMARDs; or adults with severely active RA (a DAS28 of more than 5.1), who have an inadequate response to, or who cannot have, other DMARDs, including at least one biologic agent, and who cannot have rituximab; or adults with severely active RA who have an inadequate response to rituximab and at least one biologic agent.[180] NICE recommends that filgotinib can be used as monotherapy when methotrexate is contraindicated, or if people cannot tolerate it, in these three specific patient groups.[180] The Food and Drug Administration (FDA) rejected approval of filgotinib due to concerns about testicular toxicity, and the manufacturer is no longer pursuing FDA approval.

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.[181] These results suggest that RNA sequencing-based stratification of RA synovial tissue is more strongly associated with clinical response than histopathologic classification; further research is required before treatment recommendations can be made.

Olokizumab

Olokizumab, an investigational humanized 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.[182][183][184] 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.[184] Further large randomized controlled trials are needed to establish long term effects.[183]

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.[185] 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 antirheumatic drugs (DMARDs).[186] 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.[187]