Efficacy and safety of low-dose interleukin-2 in combination with methotrexate in patients with active rheumatoid arthritis:a randomized,double-blind,placebo-controlled phase 2 trial

Rheumatoid arthritis(RA)is an aggressive autoimmune arthritis,and current therapies remain unsatisfactory due to low remission rate and substantially adverse effects.Low-dose interleukin-2(Ld-IL2)is potentially a therapeutic approach to further improve the disease.This randomized,double-blind,placebo-controlled trial was undertaken to evaluate the efficacy and safety of Ld-IL2 in patients with active RA.Patients were randomly assigned(1:1)to receive Ld-IL2,defined as a dose of 1 million IU,or placebo in a 12-week trial with a 12-week follow-up.Three cycles of Ld-IL2 or placebo were administered subcutaneously every other day for 2 weeks(a total of 7 doses),followed by a 2-week break.All patients received a stable dose of methotrexate(MTX).The primary outcomes were the proportion of patients achieving the ACR20,DAS28-ESR<2.6,and the change from baseline in CDAI or SDAI at week 24.Secondary endpoints included other clinical responses and safety.The primary outcomes were achieved in the perprotocol population.The improvements from baseline in CDAI and SDAI were significantly greater across time points for the LdIL2+MTX group(n=17)than for the placebo+MTX group(n=23)(P=0.018 and P=0.015,respectively).More patients achieved ACR20 response in the Ld-IL2+MTX group than those in the placebo+MTX group at week 12(70.6%vs 43.5%)and at week 24(76.5%vs 56.5%)(P=0.014).In addition,low Treg and high IL-21 were associated with good responses to Ld-IL2.Ld-IL-2 treatment was well-tolerated in this study.These results suggested that Ld-IL2 was effective and safe in RA.ClinicalTrials.gov number:NCT 02467504.

Altered influenza virus haemagglutinin(HA)-derived peptide is potent therapy for CIA by inducing Th1 to Th2 shift

There has been an increase in interest in the use of altered peptides as antigen-specific therapeutic agents in autoimmune diseases.Here we investigated the inhibitory effect and possible mechanism of an altered influenza virus haemagglutinin(HA)-derived peptide in collagen-induced arthritis(CIA).CIA was induced in DBA/1 mice by immunisation with type II collagen(CII).Altered HA308-317,wild-type HA308-317 or irrelevant peptide was administered intranasally beginning from arthritis onset.Clinical and histological scores were assessed,and cytokine levels in the serum or supernatants from splenocytes were determined.The percentages of Th1 and Th2 cells in response to different peptides were analysed by FACS both in vivo and in vitro.Our results showed that intranasal administration of altered HA308-317 peptide significantly ameliorated CIA.The therapeutic effect of altered HA308-317 peptide was associated with a substantial decrease in production of interferon(IFN)-c,interleukin(IL)-6,monocyte chemoattractant protein(MCP)-1,anti-CII IgG,IgG1 and IgG2a antibodies,and an markedly increase in production of IL-10 and IL-4 in serum or supernatants from splenocytes treated with altered HA308-317 peptide.The percentage of Th2(CD41IL-41)cells was upregulated significantly by altered HA308-317 peptide with a decreased percentage of Th1(T helper 1;CD41INF-c1)cells both in vivo and in vitro.These findings suggest that altered HA308-317 peptide might be a promising candidate for rheumatoid arthritis(RA)treatment.