L5 - Efficacy and Safety of Subcutaneous Recombinant Chaperonin10 in Patients with Active Rheumatoid Arthritis
Background/Purpose: Chaperones/heat shock proteins function at a variety of stages in the immune response and their expression is elevated in conditions including inflammatory autoimmune diseases. Results from a previously published trial [1] showed intravenous Cpn10 to have efficacy and safety in the treatment of RA. This study aimed to assess the efficacy and safety of a twice weekly subcutaneous (SC) formulation of Chaperonin10 (Cpn10) in patients with active RA despite MTX therapy.
Methods: 155 patients with active RA on stable methotrexate (MTX) (10 – 30 mg/wk) were randomised to receive 25 mg, 75 mg or placebo Cpn10 administered SC twice weekly for 12 wks, followed by a 12 wk extension phase. The primary endpoint was ACR20 at wk 12; ACR50/70 responses, DAS28, ACR-N, time to ACR20/50/70 and EULAR responses, mean changes in components of ACR and SF36 were also assessed. Pharmacokinetic exposure and pharmacodynamic responses to Cpn10 were assessed by measuring serum Cpn10 levels and pro-inflammatory cytokine levels, respectively. AEs and lab values were monitored for safety in all patients.
Results: At 12 weeks there were no significant differences between treatment groups in ACR responses. However, significant and dose- related changes were evident between placebo and 75mg Cpn10 in the following: ACR-N response (p<0.05, figure1); time to ACR50 response; tender and swollen joint counts; SF-36 general health, social functioning and role emotional domains, mental component score, and SF-6D health utility index. Serum IL-6 levels were significantly reduced. In those subjects who remained blinded to treatment, a significant reduction in ESR levels was seen at week 24.
*p<0.05
Most common AEs were injection site reactions, more frequent at the 75mg dose; headache, urinary and upper respiratory tract infections, more common at the 25mg dose. SAEs (4) in Cpn10 treated groups included hospitalizations for a pulmonary embolism (wk 2 of trial), pain in extremity (thrombophlebitis ruled out), a chest infection, and a fatal MI (unrelated).
Conclusions: This trial supports a previously published IV administration study and provides further evidence that short term Cpn10 therapy is well tolerated and beneficial in treatment of active RA despite MTX therapy. Cpn10 treatment was associated with significant reductions in clinical measures of RA and circulating levels of biomarkers. Future trials are planned to determine the optimal dose range and route of administration to maximize efficacy.
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