Antibodies Directed against a Peptide Epitope of a Klebsiella pneumoniae-Derived Protein Are Present in Ankylosing Spondylitis

Ankylosing spondylitis (AS) is a chronic inflammatory arthritis of unknown origin. Its autoimmune origin has been suggested but never proven. Several reports have implicated Klebsiella pneumoniae as a triggering or perpetuating factor in AS; however, its role in the disease pathogenesis remains debated. Moreover, despite extensive investigations, a biomarker for AS has not yet been identified. To clarify these issues, we screened a random peptide library with pooled IgGs obtained from 40 patients with AS. A peptide (AS peptide) selected from the library was recognized by serum IgGs from 170 of 200 (85%) patients with AS but not by serum specimens from 100 healthy controls. Interestingly, the AS peptide shows a sequence similarity with several molecules expressed at the fibrocartilaginous sites that are primarily involved in the AS inflammatory process. Moreover, the peptide is highly homologous to a Klebsiella pneumoniae dipeptidase (DPP) protein. The antibody affinity purified against the AS peptide recognizes the autoantigens and the DPP protein. Furthermore, serum IgG antibodies against the Klebsiella DPP121-145 peptide epitope were detected in 190 of 200 patients with AS (95%), 3 of 200 patients with rheumatoid arthritis (1.5%) and only 1 of 100 (1%) patients with psoriatic arthritis. Such reactivity was not detected in healthy control donors. Our results show that antibodies directed against an epitope of a Klebsiella pneumoniae-derived protein are present in nearly all patients with AS. In the absence of serological biomarkers for AS, such antibodies may represent a useful tool in the diagnosis of the disease

Treating spondyloarthritis, including ankylosing spondylitis and psoriatic arthritis, to target: recommendations of an international task force

Background: Therapeutic targets have been defined for diseases like diabetes, hypertension or rheumatoid arthritis and adhering to them has improved outcomes. Such targets are just emerging for spondyloarthritis (SpA). Objective: To define the treatment target for SpA including ankylosing spondylitis and psoriatic arthritis (PsA) and develop recommendations for achieving the target, including a treat-to-target management strategy. Methods: Based on results of a systematic literature review and expert opinion, a task force of expert physicians and patients developed recommendations which were broadly discussed and voted upon in a Delphi-like process. Level of evidence, grade and strength of the recommendations were derived by respective means. The commonalities between axial SpA, peripheral SpA and PsA were discussed in detail. Results: Although the literature review did not reveal trials comparing a treat-to-target approach with another or no strategy, it provided indirect evidence regarding an optimised approach to therapy that facilitated the development of recommendations. The group agreed on 5 overarching principles and 11 recommendations; 9 of these recommendations related commonly to the whole spectrum of SpA and PsA, and only 2 were designed separately for axial SpA, peripheral SpA and PsA. The main treatment target, which should be based on a shared decision with the patient, was defined as remission, with the alternative target of low disease activity. Follow-up examinations at regular intervals that depend on the patient's status should safeguard the evolution of disease activity towards the targeted goal. Additional recommendations relate to extra-articular and extramusculoskeletal aspects and other important factors, such as comorbidity. While the level of evidence was generally quite low, the mean strength of recommendation was 9-10 (10: maximum agreement) for all recommendations. A research agenda was formulated. Conclusions: The task force defined the treatment target as remission or, alternatively, low disease activity, being aware that the evidence base is not strong and needs to be expanded by future research. These recommendations can inform the various stakeholders about expert opinion that aims for reaching optimal outcomes of SpA

The effectiveness and safety of TNF-alpha blockers in the treatment of early psoriatic arthritis: an Italian multicentre longitudinal observational pilot study

The objective of this study is to assess the effectiveness and safety of TNF-α blockers in a group of early psoriatic arthritis (PsA) patients with an unsatisfactory response to previous conventional treatment consecutively enrolled in five Italian centres. A 24-week open-label trial was carried out in consecutive early PsA patients classified according to the CASPAR criteria, with unsatisfactory response to previous treatments and with a DAS28 threshold as ≥3.2, seen at the outpatient clinics of each centre. Exclusion criteria were previous usage of TNF-α blockers and a disease duration >12 months. The choice of any of the three TNF-α blockers was decided by the expert’s opinion, without any restriction. Effectiveness was considered as an improvement of DAS28 at 12 and 24 weeks of treatment. Secondary endpoints were an improvement of TJC, SWJ, HAQ score and PASI score. Changes from baseline to the 12- and 24-week follow-up assessments were analysed using the Wilcoxon paired sign rank test. Twenty-nine patients (14 males, 15 females, median age 37 years, range 20–65 years) were enrolled. A statistical improvement of the DAS28 was observed at 12 and 24 weeks from baseline (p < 0.001). Secondary endpoints also confirmed the effectiveness of the TNF-α blockers in the treatment of early PsA. No severe adverse events were observed during the treatment period, and no patient withdrew from the medications. This study suggests that the TNF-α blockers can be effective in the management of early PsA. Further controlled studies will provide more data on this challenging topic

Multidisciplinary Management of Spondyloarthritis-Related Immune-Mediated Inflammatory Disease

Immune-mediated inflammatory diseases (IMIDs) are chronic autoimmune conditions that share common pathophysiologic mechanisms. The optimal management of patients with IMIDs remains challenging because the coexistence of different conditions requires the intervention of several specialists. The aim of this study was to develop a series of statements defining overarching principles that guide the implementation of a multidisciplinary approach for the management of spondyloarthritis (SpA)-related IMIDs including SpA, psoriasis, psoriatic arthritis, Crohn's disease, ulcerative colitis and uveitis

Patient-reported impact of spondyloarthritis on work disability and working life: The ATLANTIS survey

44noopenopenRamonda, Roberta; Marchesoni, Antonio; Carletto, Antonio; Bianchi, Gerolamo; Cutolo, Maurizio; Ferraccioli, Gianfranco; Fusaro, Enrico; De Vita, Salvatore; Galeazzi, Mauro; Gerli, Roberto; Matucci-Cerinic, Marco; Minisola, Giovanni; Montecucco, Carlomaurizio; Pellerito, Raffaele; Salaffi, Fausto; Paolazzi, Giuseppe; Sarzi-Puttini, Piercarlo; Scarpa, Raffaele; Bagnato, Gianfilippo; Triolo, Giovanni; Valesini, Guido; Punzi, Leonardo; Olivieri, Ignazio; Ortolan, Augusta; Lorenzin, Mariagrazia; Frallonardo, Paola; Giollo, Alessandro; Locaputo, Antonella; Paolino, Sabrina; Simone, Davide; Quartuccio, Luca; Bartoloni, Elena; Luca, Rossella De; Bartoli, Francesca; Sensi, Felice; Caporali, Roberto; Carlo, Marco Di; Roberto, Bortolotti; Atzeni, Fabiola; Costa, Luisa; Ciccia, Francesco; Perrotta, Fabio; Gilio, Michele; ATLANTIS study groupRamonda, Roberta; Marchesoni, Antonio; Carletto, Antonio; Bianchi, Gerolamo; Cutolo, Maurizio; Ferraccioli, Gianfranco; Fusaro, Enrico; De Vita, Salvatore; Galeazzi, Mauro; Gerli, Roberto; Matucci-Cerinic, Marco; Minisola, Giovanni; Montecucco, Carlomaurizio; Pellerito, Raffaele; Salaffi, Fausto; Paolazzi, Giuseppe; Sarzi-Puttini, Piercarlo; Scarpa, Raffaele; Bagnato, Gianfilippo; Triolo, Giovanni; Valesini, Guido; Punzi, Leonardo; Olivieri, Ignazio; Ortolan, Augusta; Lorenzin, Mariagrazia; Frallonardo, Paola; Giollo, Alessandro; Locaputo, Antonella; Paolino, Sabrina; Simone, Davide; Quartuccio, Luca; Bartoloni, Elena; Luca, Rossella De; Bartoli, Francesca; Sensi, Felice; Caporali, Roberto; Carlo, Marco Di; Roberto, Bortolotti; Atzeni, Fabiola; Costa, Luisa; Ciccia, Francesco; Perrotta, Fabio; Gilio, Michele; ATLANTIS study, Grou

Ankylosing spondylitis and psoriatic arthritis: clinical and economic consequences of the use of etanercept

Spondyloarthritis (SpA) is the name for a family of inflammatory rheumatic disease that can affect the spine and joints, ligaments and tendons. Spondyloarthritis disease include ankylosing spondylitis, reactive arthritis, psoriatic arthritis, the spondylitis associated with the inflammatory bowel diseases and the undifferentiated spondyloarthritis. The most common treatments prescribed for spondyloarthritis are nonsteroidal anti-inflammatory drugs (NSAIDs) given in combination with disease-modifying antirheumatic drugs (DMARDs). Due to a recently suggested role of the tumour necrosis factor (TNFa) in the pathogenesis of SpA, new therapies specifically blocking TNFa have been investigated. Anti-TNF medications currently available on the Italian market are etanercept, infliximab and adalimumab. The aim of the present work was to furnish a clinical and pharmaco-economical profile of etanercept in treatment of psoriatic arthritis and ankylosing spondylitis based on a review of the published literature. Economical evaluations performed in several countries indicate that total treatment costs are lower with etanercept and adalimumab as compared to infliximab, mainly because of differences in the route of administration. Etanercept appears to be cost effective for the treatment of psoriatic arthritis and ankylosing spondylitis especially considering improved health related quality of life and lower medical costs due to superior efficacy of treatment