Scintigraphic detection of TNF-driven inflammation by radiolabelled certolizumab pegol in patients with rheumatoid arthritis and spondyloarthritis

Background: Biologicals are the cornerstone for many treatment algorithms in inflammatory arthritis. While tumour necrosis factor (TNF) inhibitors may achieve important responses in similar to 50% of patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA), a significant fraction of patients are partial or non-responders. We hypothesised that in vivo assessment of TNF by scintigraphy with 99mTc-radiolabelled certolizumab pegol (CZP) might lead to a more 'evidence-based biological therapy'. Objectives: Our goal was to perform a proof-of-concept study of in vivo detection of TNF by immunoscintigraphy of a radiolabelled TNF inhibitor in RA and SpA, and correlate this with clinical, imaging findings and therapeutic outcome. Methods: CZP was conjugated with succinimidyl-6-hydrazino-nicotinamide and subsequently radiolabelled with Tc99m. Whole body and static images of hands, feet and sacroiliac joints of 20 patients (5 RA; 15 SpA) were acquired at 3 time points. Immunoscintigraphic findings were scored semiquantitatively. Subsequently, all patients were treated with CZP. Results: In peripheral joints, clinically affected joints or abnormal ultrasound findings were observed more frequently (p<0.001) in the scintigraphic-positive group. In patients with axial SpA, bone marrow edema on MRI was detected more frequently (p<0.001) in quadrants with tracer uptake. At the patient level, the odds of a joint remaining tender despite 24 weeks of CZP treatment was significantly smaller in joints with clear tracer uptake as compared with those with no uptake (OR=0.42, p=0.04). Conclusions: Immunoscintigraphy with radiolabelled CZP demonstrated both axial and peripheral inflammation, and displayed good correlation with clinical features, conventional imaging and therapy response

Peripheral manifestations in spondyloarthritis: relevance for diagnosis, classification and follow-up

Purpose of review : The field of spondyloarthritis (SpA) has evolved enormously over the last few years, starting with the advent of biological therapies at the end of the previous millenium. A lot of work has been done to construct valid outcome measures and treatment guidelines based upon the results of pivotal studies with Tumor necrosis factor (TNF)-blocking agents. Most of these trials were performed in well described populations, such as patients suffering from ankylosing spondylitis (AS) or psoriatic arthritis. Recent findings : Over recent years a reappraisal has been done with regard to considering again the full spectrum of diseases belonging to the SpA concept, especially in early disease stages. This effort culminated in the construction of new classification criteria for axial and peripheral SpA. Around the same time, a number of patient registries were set up, allowing the follow-up of patients in order to study the natural evolution of patients classified early. The first data from these cohorts provide interesting information on peripheral joint manifestations such as arthritis, enthesitis or dactylitis. Recognition and monitoring of these manifestations are essential for clinicians in order to provide comprehensive patient care. Summary : There is a growing interest in the field of SpA to move from rather restricted and longstanding diseases such as AS to a more comprehensive view, encompassing not only inflammatory back pain, but also peripheral arthritis and enthesitis, as well as extra-articular manifestations. The new classification criteria and guidelines for follow-up are applied now in a number of prospective patient registries, and provide us with valuable information on the early disease stages of SpA

Osteoarticular manifestations: specific treatments and/or treating intestinal disease?

Osteoarticular manifestations in inflammatory bowel diseases (IBD) belong to the concept of spondyloarthritis (SpA) including an axial and peripheral SpA according to predominant symptoms (inflammatory back pain vs. peripheral arthritis and enthesopathy). Careful examination of sacroiliac joints on MRI plays a crucial role in the recognition of an early axial SpA in young patients with inflammatory back pain and spinal inflammation on MRI but without structural changes on radiography (non-rx SpA). In this early form of SpA, chronic gut inflammation was already found in about 30% of patients. Moreover, more pronounced bone marrow edema was found in patients with axial SpA and chronic gut inflammation. Identification of a therapeutic window in patients with early gut and spine inflammation is important since anti-TNF suppresses inflammation and seems to prevent evolution to structural changes. Shared genetic factors probably predispose to both diseases. Careful analysis of the effect of medication on gut and spine inflammation in SpA and IBD patients is recommended in order to find new therapeutic agents.</jats:p

Spondyloarthritis and inflammatory bowel disease: comorbidity and treatment implications

Spondyloarthritides (SpA) and inflammatory bowel disease (IBD) are chronic, idiopathic inflammatory disorders of the axial and peripheral joints and the intestinal tract, respectively, affecting up to 1 % of the population. There is clinical and genetic evidence supporting some degree of overlap between the pathogenesis of these two entities. Nevertheless, their treatment is at times conflicting. NSAIDs, although useful in SpA, are considered to be possible risk factors for flares in IBD. Moreover, etanercept, a soluble TNF receptor blocker used in SpA, is ineffective in IBD. As patients with SpA often develop microscopic gut inflammation, it is important to understand the impact on disease progression or even therapeutic response. Further research is mandatory in this regard

Relevance of the gut/joint axis for the management of spondyloarthritis in daily clinical practice

Purpose of review : Thirty years ago, the concept of microscopic gut inflammation in spondyloarthritis (SpA) was established. Over the past decade, there has been tremendous progress in the earlier diagnosis of SpA. In addition, it has been suggested that, because of improved hygiene over the past years, exposure to microorganisms has changed, leading to a shift in diseases, for example, a decreased incidence of reactive arthritis. It is therefore necessary to re-establish the role of gut inflammation in SpA. Recent findings : The prevalence of microscopic gut inflammation could be confirmed in c. 50% of patients with early axial and/or peripheral SpA. More importantly, a predictive model could be developed linking gut inflammation with clinical factors, that is, higher disease activity, extensive sacroiliac bone marrow edema, and progressive disease. In addition, there is increasing evidence indicating that the presence or absence of gut inflammation in SpA may influence therapeutic decision-making in the future. A clear demonstration of this is the different efficacy of IL-17 blockade in Crohn's disease versus SpA. Summary : Microscopic gut inflammation is present in almost 50% of SpA patients and appears relevant for prognosis and therapeutic decision-making. SpA patients with the chronic type of gut inflammation seem to have a less favorable disease course. It is therefore conceivable that assessment of gut inflammation should be included in future models for risk stratification of SpA

Mucosal inflammation in spondylarthritides : past, present, and future

Spondylarthritides (SpA) and inflammatory bowel disease (IBD) are idiopathic, chronic inflammatory disorders. Although they are very distinct and well-defined entities, there is clinical and genetic evidence supporting some degree of overlap between the pathogenesis of the two. Subclinical gut inflammation is present in up to two thirds of all SpA patients and can evolve into IBD. This subclinical gut inflammation has been shown to be strongly associated with joint inflammation, providing a clue for a common pathophysiologic background. Despite extensive research progress in the field over the past few years, many questions remain unanswered. In this paper, we focus on the clinical, genetic, and pathophysiologic overlap of SpA and IBD. Furthermore, we discuss some of the targets that may influence therapeutic decision making

Renvoi précoce au spécialiste de patients avec une suspicion de spondylo- arthropathie axiale en première ligne: Les résultats belges de l'étude RADAR

Currently, there is a 5 to 7 years gap between the first symptoms and the diagnosis of ankylosing spondylitis. A better patient referral might reduce this gap and accelerate the adequate treatment implementation. The study objective was to compare 2 referral strategies used in first line. In Belgium, 208 referral physicians assigned to 16 rheumatology centres were randomized to refer chronic back pain patients (with onset <45 years) using 1 of the 2 referral strategies :Strategy 1 :1 of 3 criteria (inflammatory back pain, HLA-B27, sacroiliitis on imaging); or Strategy 2 :2 of 6 criteria (IBP inflammatory back pain, HLA-B27, sacroiliitis, family history, good response to NSAIDs, extra-articular manifestations). Among the 141 refer red patients with strategy 1 and 2, 26.0 and 36.9% respectively were diagnosed with Axial Spondylarthritis (SpA). Inflamma tory back pain, sacroiliitis and good respond to NSAIDs were the most frequently used criteria (92.9%, 36.2% and 33.3% respectively). This study emphasizes the high prevalence of undiagnosed axial SpA in patients with chronic back pain and stressed the necessity to increase awareness of the disease.SCOPUS: ar.jinfo:eu-repo/semantics/publishe