Search

Summary Background Ixekizumab, a high-affinity interleukin-17A (IL-17A) monoclonal antibody, has previously shown efficacy in radiographic axial spondyloarthritis (also known as ankylosing spondylitis). We aimed to evaluate the efficacy and safety of ixekizumab, an IL-17 inhibitor, in non-radiographic axial spondyloarthritis. Here, we report the primary results of COAST-X. Methods COAST-X was a 52-week, randomised, double-blind, placebo-controlled, parallel-group study done at 107 sites in 15 countries in Europe, Asia, North America, and South America. Eligible participants were adults (aged ≥18 years) with active axial spondyloarthritis without definite radiographic sacroiliitis (non-radiographic axial spondyloarthritis), objective signs of inflammation (via MRI or C-reactive protein), and an inadequate response or intolerance to non-steroidal anti-inflammatory drugs (NSAIDs). Patients were randomly assigned (1:1:1) to receive subcutaneous 80 mg ixekizumab every 4 weeks (Q4W) or every 2 weeks (Q2W), or placebo. Changing background medications or switching to open-label ixekizumab Q2W, or both, was allowed after week 16 at investigator discretion. Primary endpoints were Assessment of SpondyloArthritis international Society-40 (ASAS40) response (defined as an improvement of 40% or more and an absolute improvement from baseline of 2 units or more [range 0–10] in at least three of the four domains [patient global, spinal pain, function, and inflammation] without any worsening in the remaining one domain) at weeks 16 and 52. Patients who switched to open-label ixekizumab were imputed as non-responders in logistic regression analysis. This trial is registered with ClinicalTrials.gov , number NCT02757352 . Findings Between Aug 2, 2016, and Jan 29, 2018, 303 patients were enrolled (105 to placebo, 96 to ixekizumab Q4W, and 102 to ixekizumab Q2W). Both primary endpoints were met: ASAS40 at week 16 (ixekizumab Q4W: 34 [35%] of 96, p=0·0094 vs placebo; ixekizumab Q2W: 41 [40%] of 102, p=0·0016; placebo: 20 [19%] of 105) and ASAS40 at week 52 (ixekizumab Q4W: 29 [30%] of 96, p=0·0045; ixekizumab Q2W: 32 [31%] of 102, p=0·0037; placebo: 14 [13%] of 105). 60 (57%) of 104 patients in the placebo group, 63 (66%) of 96 in the ixekizumab Q4W group, and 79 (77%) of 102 in the ixekizumab Q2W group had at least one treatment-emergent adverse event. The most common treatment-emergent adverse events in the ixekizumab groups were nasopharyngitis and injection site reaction. Of the treatment-emergent adverse events of special interest, there was one case of serious infection in the ixekizumab Q4W group. The frequency of serious adverse events was low (four [1%] of 302) and similar across the three groups. There were no malignancies or deaths. No new safety signals were identified. Interpretation Ixekizumab was superior to placebo for improving signs and symptoms in patients with non-radiographic axial spondyloarthritis at weeks 16 and 52. Reports of adverse events were similar to those of previous ixekizumab studies. Ixekizumab offers a potential therapeutic option for patients with non-radiographic axial spondyloarthritis who had an inadequate response or were intolerant to NSAID therapy. Funding Eli Lilly and Company.

The aim of this study was to describe the use of (99m)Tc-anti-TNF-α scintigraphy for detecting inflammation of the sacroiliac joints in a patient with non-radiographic axial spondyloarthritis. A 47-year-old female patient, non-smoker and non-drinker, complained of a low back pain inflammation, which began 4 years before her condition have exacerbated to morning stiffness and anterior uveitis in the last 6 months. Initially diagnosed as mechanical low back pain, she irregularly took non-steroidal anti-inflammatory drugs and corticosteroids, without significant long-lasting results. Radiographic findings were negative. There was increased uptake of (99m)Tc-anti-TNF-α in an area corresponding to the topography of ileum and sacroiliac right joint upon (99m)Tc-anti-TNF-α scintigraphy. Magnetic resonance imaging (MRI), the most used image diagnosis tool, showed minimum impregnation of gadolinium in the right sacroiliac joint and at the iliac face of the inferior third of the right sacroiliac joint. We suggest that (99m)Tc-anti-TNF-α can facilitate early diagnosis of patients with non-radiographic axial spondyloarthritis. More studies are now ongoing.

Objective. To compare the use of radiolabelled human monoclonal anti-TNF-a scintigraphy with clinical examination and MRI of hands and wrists joints in patients with active RA. Methods. Eight patients with active RA, 28-joint DAS (DAS-28)5 3.2 and a healthy volunteer underwent whole body and hand/wrist scintigraphy after the administration of anti-human TNF-a labelled with technetium-99m ( 99m Tc). One hundred and ninety-eight joints were examined. Patients were also given clinical examinations in addition to MRI of the hands and wrists. Results. Of the 198 joints examined, signs of inflammation were detected by MRI in 49 (24.7%) and by scintigraphy in 48 (24.2%) joints, with agreement between the two methods in 44 joints. In five joints, MRI was positive and scintigraphy negative. In another four joints, scintigraphy was positive and MRI negative for signs of inflammation. MRI and scintigraphy were in agreement for negative results for 145 joints. The sensitivity and specificity of scintigraphy was 89.8 and 97.3%, respectively. When clinical parameters (presence of swelling and tenderness of joints) were compared with the MRI findings, lower correlation coefficients were observed (sensitivity of 59.2% and 65.3%, respectively). Conclusions. Scintigraphy using 99m Tc-anti-TNF-a showed high correlation with the presence of inflammatory signs detected by MRI in the hands and wrists of patients with active RA, and demonstrated a greater sensitivity than clinical examination. These results can assist in better understanding of anti-cytokine therapy and support the achievement of evidence-based biologic therapy.

We read the letter from Colavita, et al 1, where the authors show by in vitro experiments that human osteoblast-like SV-40 T antigen immortalized (HOBIT) cells are productively infected by Zika virus (ZIKV). Their experiments with HOBIT cells infected with both Asian and African Zika strains show that both viruses are indeed able to produce a fair amount of virus 96 h postinfection. It is interesting that ZIKV could replicate in a HOBIT … Address correspondence to Dr. L. Roimicher, Department of Rheumatology–Internal Medicine, Hospital Universitario CFF, Universidade Federal do Rio de Janeiro, Rua Prof Rodolpho Paulo Rocco 255, 70 Andar, Rio de Janeiro, Brazil. E-mail: mail-luizroimicher{at}gmail.com

To the Editor: Since 2015, Brazil has experienced a major public health crisis caused by the arboviruses Zika (ZIKV) and Chikungunya (CHIKV), which are circulating along with the dengue virus1. ZIKV is now considered endemic in all Brazilian states and is currently spreading widely in South and Central America and is threatening the United States and Europe2,3. ZIKV and CHIKV share similar acute clinical presentation with arthralgia, skin rash, and fever, which also resembles other rheumatic diseases1,4. Most relevantly, ZIKV and CHIKV may complicate the clinical condition of rheumatic patients. We share here the case of a 53-year-old woman with a … Address correspondence to Dr. L. Roimicher, Department of Rheumatology–Internal Medicine, Hospital Universitario CFF, Universidade Federal do Rio de Janeiro, Rua Prof Rodolpho Paulo Rocco 255, 70 Andar, Rio de Janeiro, Brazil. E-mail: mail-luizroimicher{at}gmail.com