Response to netakimab in radiographic axial spondyloarthritis patients with different baseline C-reactive protein, sacroiliitis evaluated by MRI and peripheral joint involvement status: a post-hoc analysis of the ASTERA study.

OBJECTIVES: Netakimab is a humanised camelid-derived monoclonal antibody targeting interleukin-17A. Here, we report the results of post-hoc analysis of the ASTERA phase 3 study (NCT03447704, February 27, 2018) in patients with active radiographic axial spondyloarthritis (r-axSpA) grouped by baseline C-reactive protein (CRP), baseline sacroiliac joint (SIJ) inflammation through magnetic resonance imaging (MRI) or presence of peripheral arthritis (PA). METHODS: In this double-blinded, multicentre, randomised, placebo-controlled, phase 3 ASTERA study, 228 adult patients with active r-axSpA received 120 mg of subcutaneous netakimab or placebo at weeks 0, 1, 2, and thereafter every other week. For the subanalysis, 16-week data of 114 netakimab-treated patients with the available baseline CRP and SIJ MRI were grouped by normal (<5 mg/L) or abnormal (≥5 mg/L) CRP, by the grade of sacroiliitis (SI) based on the SPARCC MRI score <2 (MRI-SI-) or ≥2 (MRI-SI+), or by the presence of PA. ASAS-recommended activity, spinal mobility, and function endpoints for r-axSpA were analysed. RESULTS: At week 16, an improvement in all the outcomes was similar for MRI-SI- and MRI-SI+ patients, except for a change in ASspi-MRI-a which was significantly greater in MRI-SI+. Netakimab was effective regardless of baseline CRP and PA. For patients with CRP ≥5 mg/L, a more pronounced decline in r-axSpA activity was observed with a trend towards the most prominent improvement in ASDAS-CRP and BASDAI for patients with CRP >20 mg/L. CONCLUSIONS: Subcutaneous netakimab is effective in patients with r-axSpA irrespective of baseline CRP and inflammation on SIJ MRI. The benefit in patients with high CRP (>20 mg/L) was more pronounced.

DNA-hydrolysing activity of IgG antibodies from the sera of patients with diseases caused by different bacterial infections.

DNase autoantibodies (Abs) can be found in the blood of patients with several autoimmune diseases, while the blood of healthy donors or patients with diseases with insignificant disturbances of the immune status does not contain the DNase Abs. Here we have analysed for the first time the DNase activity in the patients with diseases caused by several bacterial infections. Several rigid criteria have been applied to show that the DNase activity is an intrinsic property of IgGs from the sera of patients with bacterial diseases but not from healthy donors. The relative activity of IgGs has been shown to vary extensively between the diseases analysed and from patient to patient, but most of the preparations had detectable levels of the DNase activity. On average, the catalytic activities were significantly lower than in patients with autoimmune pathologies and increased in the following order: streptococcal infection (erysipelas) < urogenital chlamydiosis associated with arthritis (Reiter's disease) < meningococcal meningitis < shigellosis < suppurative surgical infections caused by Staphylococcus aureus < suppurative surgical infections caused by epidermal staphylococci < urogenital ureaplasmosis associated with reactive arthritis. While intact IgGs possessed this catalytic activity, separated light chains of polyclonal Abs appeared to be even more active in the hydrolysis of DNA.