Promising RA Treatments
Despite improved drugs for RA, a large proportion of patients still do not achieve remission with current strategies. Presentation of results on novel therapeutics, such as baricitinib and mavrilimumab, highlighted some exciting advances.
Dougados and colleagues[6] presented results from a 24-week global, phase 3 trial of baricitinib, an oral Janus kinase (JAK)1/JAK2 inhibitor, in patients with RA who had an inadequate response or were intolerant to one or more conventional disease-modifying antirheumatic drugs (DMARDs). Genovese and colleagues[7] presented another phase 3 trial of baricitinib in patients with active RA who had an inadequate response to or were intolerant of one or more tumor necrosis factor (TNF) inhibitors.
In both trials, rapid and sustained clinical improvements were seen in a dose-dependent manner. Baricitinib had an acceptable safety and tolerability profile, suggesting that this drug is a promising upcoming therapeutic option.
Burmester and colleagues[8] presented results from a 24-week phase 2b trial of mavrilimumab, a granulocyte-macrophage colony-stimulating factor receptor-alpha inhibitor, in patients with moderate to severe adult-onset RA. The drug was well tolerated and the study met its co-primary endpoints, which were significant changes in Disease Activity Score (DAS) 28-CRP through week 12 and American College of Rheumatology 20% improvement criteria (ACR20) response at week 24.
However, there were also some disappointments at this year's meeting. In a phase 2 study, neither ustekinumab, an anti–interleukin (IL)-12/23p40 monoclonal antibody, nor guselkumab, an anti–IL-23p19 monoclonal antibody, demonstrated significant efficacy in improving signs and symptoms of active RA on the basis of ACR20 response at week 28 among patients with active RA despite treatment with methotrexate.[9]
There were also some new developments in alternative treatment regimens with approved agents, such as tocilizumab. The U-Act-Early strategy study reported by Bijlsma and colleagues[10] was designed to compare the sustained remission rates of a treat-to-target strategy with (1) tocilizumab, an IL-6 receptor antagonist, combined with methotrexate; (2) tocilizumab monotherapy; or (3) methotrexate monotherapy, in DMARD-naive patients with early RA. The study showed up to twofold increased sustained remission rates in both tocilizumab arms compared with the methotrexate monotherapy arm.
In addition to clinical trials, preclinical studies provided new data on compelling potential therapeutic targets. McGettrick and colleagues[11] examined the ability of adiponectin, an anti-inflammatory adipose tissue-derived cytokine and a novel endogenous peptide inhibitor of transendothelial migration (PEPITEM), to regulate T-cell migration in vivo and in vitro.[11] They identified a PEPITEM-mediated pathway that suppresses T-cell recruitment across inflamed endothelium, which is dysfunctional in patients with early RA. Their hypothesis was that this dysfunction in patients with RA could result in inappropriate accumulation of T cells in the rheumatoid joint. Reestablishing PEPITEM function to turn off pathologic T-cell recruitment could therefore represent a novel therapeutic approach for early RA.
Another interesting study by Hua and colleagues[12] demonstrated that a proliferation-inducing ligand (APRIL), but not B-lymphocyte stimulator (BLyS), promoted IL-10 production by B cells and enhanced the regulatory effects of B cells on T cells by decreasing TNF-alpha and TNF-gamma secretion, providing intriguing hypotheses of possible therapeutic applications.
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Cite this: Ioannis Parodis. From Rome, the Latest in Rheumatology - Medscape - Aug 10, 2015.
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