The rheumatoid arthritis drug pipeline is robust with 243 molecules under study, but more than half end up dropping off through natural attrition.
A recent review of clinical trials for rheumatoid arthritis shows that 243 molecules are currently under study worldwide as possible treatments for this condition, according to a systemic review of clinical trials from 17 international databases.
Published in the Annals of the Rheumatic Diseases in June and recently presented at the European Congress of Rheumatology (EULAR) e-congress, the review, which was conducted in June 2019, identified 4,652 clinical trials of which 242 met the inclusion criteria for this review ultimately including 243 molecules..
“Hopefully, some of the currently evaluated drugs will contribute to improve the therapeutic management of RA patients, requiring a greater personalization of therapeutic strategies, both in the choice of molecules and their place in therapeutic sequences,” wrote author Julien Blaess, of Hôpitaux Universitaires de Strasbourg in France.
Rheumatoid arthritis has an incidence rate of 0.5-1 percent, however only 40 percent of patients are ACR70 responders, which indicates a need for more effective treatment options, the authors wrote. Th drug development process is a complex one and in this review, 141 of the 242 clinical trials were withdrawn through attrition.
Among trials for conventional synthetic (cs) DMARDs, there were 21 with eight withdrawn; there were 117 clinical trials for biologic (b) DMARD with 69 withdrawn; and there were 105 clinical trials for targeted synthetic (ts) DMARDs with 64 being withdrawn.
Among the csDMARDs molecules: 4 were already approved for RA and nine were in development (one in phase I/II, five in phase II and three in phase IV).
Among the bDMARDs, 59 percent have been withdrawn; 8 percent are labeled in rheumatoid arthritis, including abatacept, adalimumab, anakinra, certolizumab, etanercept, golimumab, infliximab, rituximab, sarilumab and tocilizumab; and 33 percent are in development, with 3 percent in a phase 4 trial. The bDMARDs currently in development target B cells, T cells, T/B cells costimulation, tumor necrosis factor alpha, interleukin (IL)-1, IL-6, IL-17, IL-23, granulocyte-macrophage colony-stimulating factor, other cytokines or chemokines, integrins or adhesion proteins, interferon receptor and various other targets.
For the tsDMARDs, 61 percent have been withdrawn; 6 percent have just been or will likely soon be labeled, includingbaricitinib, filgotinib, peficitinib, tofacitinib and upadacitinib; 33 percent are in development, with 3 percent in a phase 3 trial. The tsDMARDs currently under development target tyrosine kinase, janus kinase, sphingosine phostate, the PI3K pathway, phosphodiesterase-4, B cells signaling pathways and various other targets.
While nearly 250 molecules have been or are being evaluated in rheumatoid arthritis, Blaess said that “this development does not always lead to new treatments since 141 (58 percent) have already been withdrawn. Hopefully, some of the currently evaluated drugs will contribute to improve the therapeutic management of RA patients, requiring a greater personalization of therapeutic strategies, both in the choice of molecules and their place in therapeutic sequences.
AB0332 (2020)Immunosuppressive And Immonomodulating Agents In Rheumatoid Arthritis: A Systematic Review Of Clinical Trials And Their Current Development Stage. Julien Blaess.2020 EULAR E-Congress