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Objectives: The aim of this work is to verify the non-inferior efficacy and safety of CMAB008 compared with innovator infliximab in rheumatoid arthritis patients combined with methotrexate. Methods: We conducted a randomized, double-blinded, parallel, positive control design, multicenter study, with a stable dose of methotrexate. Patients were enrolled randomly with a ratio of 1:1 to receive intravenously CMAB008 3 mg/kg or innovator infliximab 3 mg/kg at weeks 0, 2, 6, 14, 22 and 30. The primary efficacy endpoint was American College of Rheumatology 20% improvement criteria (ACR20) response rate at week 30. The non-inferiority was established if the lower limit of the one-sided 97.5% confidence interval (CI) for the difference was more than − 15% and the equivalence was established if the two-sided 95% CI was within ± 15% in an exploratory equivalence analysis. The secondary endpoints included other efficacy assessment parameters, as well as immunogenicity, safety, and pharmacokinetics. Results: In the full analysis population (FAS), 110 (57.6%) of 191 patients in the CMAB008 group and 120 (62.2%) of 193 patients in the innovator infliximab group reached the primary outcome of ACR20 at week 30. The differences of the rates were − 4.6% and the lower limit of one-sided 97.5% confidence interval was − 14.29%, not less than the lower limit of the non-inferiority margin (− 15%); so CMAB008 was non-inferior to innovator infliximab. Further, CMAB008 was equivalent to innovator infliximab both in FAS (difference − 4.6%, 95% CI − 14.29% to 5.12%) and PPS (difference – 3.3%, 95% CI – 13.18% to 6.62%). The efficacy, safety, immunogenicity, and pharmacokinetics are highly similar between CMAB008 and innovator infliximab. Conclusions: Non-inferior efficacy of CMAB008 to innovator infliximab is illustrated with similar early and lasting therapeutic effects, and the equivalence is further demonstrated. CMAB008 is well tolerated and has semblable safety compared with the innovator infliximab. Trial registration number: NCT03478111.

Introduction: The aim of this work is to examine the efficacy and safety of prefilled liquid etanercept-biosimilar Yisaipu versus lyophilized Yisaipu in active ankylosing spondylitis (AS) patients. Methods: This double-blind, phase III trial with non-inferiority design randomized adult patients with active AS in a 3:1:1 ratio to receive twice-weekly 25-mg prefilled liquid Yisaipu for a total of 48 injections (group I, n= 330), once-weekly 50-mg prefilled liquid Yisaipu for 24 injections (group II, n= 110), or twice-weekly 25-mg lyophilized Yisaipu for 48 injections (group III, n= 110). Both physicians and patients who received 25-mg twice-weekly lyophilized or liquid Yisaipu were blinded to treatment assignment while patients who received 50-mg once-weekly liquid Yisaipu received treatment in an open-label design. In addition, 90 patients in the PK/PD study were randomized in a 1:1:1 ratio to each group. The primary outcome was the proportion of patients who achieved ASAS20 at week 24. Results: A total of 640 subjects were enrolled. The proportion of patients who attained ASAS20 at week 24 was 85.56% in group I, 85.71% in group II, and 83.45% in group III (group I vs. III,P= 0.545; group II vs. III, P= 0.605). The difference between group I and III was 2.10% (95% CI − 5.06%, 9.27%) and 2.26% (95% CI − 6.21%, 10.73%) between group II and III, meeting the non-inferiority threshold (Δ = − 15%) (P< 0.001). Except for a statistical difference between group I (75.83%) and group III at week 8 (64.75%, P= 0.011), there was no statistical difference in the ASAS20 attainment rate among the three groups at other time points. The incidence of serious adverse events was comparable among the three groups (group I, 2.50%, II, 2.86% and III, 1.43%; P> 0.05). No deaths were reported. Conclusions: Once-weekly 50-mg or twice-weekly 25-mg prefilled liquid Yisaipu is safe and non-inferior to twice-weekly 25-mg lyophilized Yisaipu. Trial Registration: CTR20130124 and NCT04345458.

Objective To analyse the association between serum interleukin (IL)-23 mRNA levels and clinical characteristics in patients with systemic lupus erythematosus (SLE).Methods Serum IL-23 and IL-17 mRNA levels were quantified using real-time reverse transcription–polymerase chain reaction in patients with SLE and healthy controls. Disease activity was assessed using the SLE Disease Activity Index-2k.Results A total of 108 patients with SLE and 60 control subjects were recruited. IL-23 mRNA levels were significantly higher in patients with SLE compared with healthy controls, and in patients with SLE and renal involvement compared with SLE alone. IL-23 mRNA levels were not different between patients with active or inactive SLE, but the IL-17/IL-23 ratio was significantly higher in patients with active disease. IL-17 and IL-23 mRNA levels were strongly correlated.Conclusions Serum IL-23 mRNA was elevated in patients with SLE and renal disease, and the IL-17/IL-23 ratio was higher in patients with active SLE. These findings suggest that IL-23 may play an important role in SLE pathogenesis, and that the IL-17/IL-23 ratio may be useful biomarker for active disease.

Background: Knee osteoarthritis is a common cause of musculoskeletal pain and a leading cause of disability and healthcare economic burden. The optimum treatment for knee osteoarthritis is still inconclusive. A network meta-analysis is required to assess the efficacy and safety of treatments and provide more scientific medical evidence. Methods: Relevant studies were searched through PubMed, Embase, and Cochrane Library electronic databases from the inception to October 2018. Continuous outcomes such as pain, stiffness, physical function and total scores were expressed as the mean differences with 95% credible interval. Surface under the cumulative ranking curve illustrated the rank probability of each therapy under different outcomes. Results: Nineteen studies were included in this study, with a total of 2395 patients. For knee pain, platelet-rich plasma (0.691) was ranked at the first place, followed by hyaluronic acid combined with platelet-rich plasma (0.670) and hyaluronic acid (0.402). In terms of stiffness, hyaluronic acid combined with platelet-rich plasma (0.743) enjoyed the highest value, platelet-rich plasma (0.603) was the next and hyaluronic acid (0.386) was the third. As for physical function, the rank was hyaluronic acid combined with platelet-rich plasma (0.772), platelet-rich plasma (0.608) and hyaluronic acid (0.343). For total scores, the order given by surface under the cumulative ranking was hyaluronic acid combined with platelet-rich plasma (0.765), platelet-rich plasma (0.624) and hyaluronic acid (0.37). Conclusions: Hyaluronic acid combined with platelet-rich plasma showed the best efficacy in improving stiffness, physical function, and total scores, while platelet-rich plasma appeared the best in terms of pain reduction.