Lianne S. Gensler

American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015 Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis

To provide evidence‐based recommendations for the treatment of patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (SpA).

Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1.

Ankylosing spondylitis (AS) is a common, highly heritable, inflammatory arthritis for which HLA-B*27 is the major genetic risk factor, although its role in the aetiology of AS remains elusive. To better understand the genetic basis of the MHC susceptibility loci, we genotyped 7,264 MHC SNPs in 22,647 AS cases and controls of European descent. We impute SNPs, classical HLA alleles and amino-acid residues within HLA proteins, and tested these for association to AS status. Here we show that in addition to effects due to HLA-B*27 alleles, several other HLA-B alleles also affect susceptibility. After controlling for the associated haplotypes in HLA-B, we observe independent associations with variants in the HLA-A, HLA-DPB1 and HLA-DRB1 loci. We also demonstrate that the ERAP1 SNP rs30187 association is not restricted only to carriers of HLA-B*27 but also found in HLA-B*40:01 carriers independently of HLA-B*27 genotype.

Clinical, radiographic and functional differences between juvenile-onset and adult–onset ankylosing spondylitis: results from the PSOAS cohort

Aims: Previous data suggests that patients with juvenile-onset ankylosing spondylitis (JoAS) have more severe disease and worse functional outcomes than adult-onset AS (AoAS). The purpose of this study was to evaluate clinical, functional and radiographic differences between patients with JoAS and AoAS in a large cohort of patients with long-standing disease. Methods: A total of 402 subjects who met the Modified New York Criteria for definitive AS and had had disease ⩾20 years were enrolled in a multi-centre cross-sectional study (Prospective Study of Outcomes in Ankylosing Spondylitis; PSOAS). JoAS was defined as initial symptoms ⩽16 years of age. A total of 79 subjects with JoAS and 323 subjects with AoAS were identified. An analysis of clinical and demographic comparisons between the two groups was performed including HLA B27 status. Functional outcomes were assessed by Bath AS Functional Index (BASFI) and the Health Assessment Questionnaire modified for the Spondyloarthropathies (HAQS). Radiographic disease severity was assessed by the Bath AS Radiology Index (BASRI). Results: With the exception of obvious differences in age at onset and disease duration, demographic and clinical characteristics were similar between the two groups. However, the JoAS group trended towards more women (32.9 vs 22.9%, p = 0.07). Controlling for multiple covariates including disease duration, both the BASRI hip score and the need for total hip arthroplasty (THA) was higher in the JoAS group. The BASRI spine score (including total, lumbar and cervical spine) was significantly lower in the patients with JoAS even after controlling for multiple covariates including disease duration and gender. No difference in function (BASFI or HAQS scores) between groups was identified. Conclusions: Compared to AoAS, subjects with JoAS have (1) less severe axial involvement radiographically, (2) similar functional outcomes, (3) more hip involvement with a greater need for THA, and (4) a slightly higher proportion of women.

Treating axial spondyloarthritis and peripheral spondyloarthritis, especially psoriatic arthritis, to target: 2017 update of recommendations by an international task force

Therapeutic targets have been defined for axial and peripheral spondyloarthritis (SpA) in 2012, but the evidence for these recommendations was only of indirect nature. These recommendations were re-evaluated in light of new insights. Based on the results of a systematic literature review and expert opinion, a task force of rheumatologists, dermatologists, patients and a health professional developed an update of the 2012 recommendations. These underwent intensive discussions, on site voting and subsequent anonymous electronic voting on levels of agreement with each item. A set of 5 overarching principles and 11 recommendations were developed and voted on. Some items were present in the previous recommendations, while others were significantly changed or newly formulated. The 2017 task force arrived at a single set of recommendations for axial and peripheral SpA, including psoriatic arthritis (PsA). The most exhaustive discussions related to whether PsA should be assessed using unidimensional composite scores for its different domains or multidimensional scores that comprise multiple domains. This question was not resolved and constitutes an important research agenda. There was broad agreement, now better supported by data than in 2012, that remission/inactive disease and, alternatively, low/minimal disease activity are the principal targets for the treatment of PsA. As instruments to assess the patients on the path to the target, the Ankylosing Spondylitis Disease Activity Score (ASDAS) for axial SpA and the Disease Activity index for PSoriatic Arthritis (DAPSA) and Minimal Disease Activity (MDA) for PsA were recommended, although not supported by all. Shared decision-making between the clinician and the patient was seen as pivotal to the process. The task force defined the treatment target for SpA as remission or low disease activity and developed a large research agenda to further advance the field.

Choosing wisely: The American College of Rheumatology's top 5 list of things physicians and patients should question

We sought to develop a list of 5 tests, treatments, or services commonly used in rheumatology practice whose necessity or value should be questioned and discussed by physicians and patients.

Genetic Dissection of Acute Anterior Uveitis Reveals Similarities and Differences in Associations observed with Ankylosing Spondylitis

To use high‐density genotyping to investigate the genetic associations of acute anterior uveitis (AAU) in patients with and those without ankylosing spondylitis (AS).

The Concept of Axial Spondyloarthritis: Joint Statement of the Spondyloarthritis Research and Treatment Network and the Assessment of SpondyloArthritis international Society in Response to the US Food and Drug Administration's Comments and Concerns

Atul Deodhar, MD: Oregon Health & Science University, Portland; John D. Reveille, MD: University of Texas Health Sciences Center, Houston; Filip van den Bosch, MD, PhD: Ghent University Hospital, Ghent, Belgium; Jürgen Braun, MD: Rheumazentrum Ruhrgebiet, Herne, Germany; Ruben Burgos-Vargas, MD: Hospital General de México and Universidad Nacional Autónoma de México, Mexico City, Mexico; Liron Caplan, MD, PhD: University of Colorado and Denver VA Medical Center, Denver, Colorado; Daniel O. Clegg, MD: University of Utah Medical Center, Salt Lake City; Robert A. Colbert, MD, PhD: National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland; Lianne S. Gensler, MD: University of California, San Francisco; Désirée van der Heijde, MD, PhD: Leiden University Medical Centre, Leiden, The Netherlands, and Diakonhjemmet Hospital, Olso, Norway; Irene E. van der Horst-Bruinsma, MD, PhD: VU University Medical Centre, Amsterdam, The Netherlands; Robert D. Inman, MD: Toronto Western Hospital and University of Toronto, Toronto, Ontario, Canada; Walter P. Maksymowych, MD, FRCPC: Alberta Heritage Foundation for Medical Research and University of Alberta, Edmonton, Alberta, Canada; Philip J. Mease, MD: Seattle Rheumatology Associates, Seattle, Washington; Siba Raychaudhuri, MD: University of California Davis, Sacramento; Andreas Reimold, MD: University of Texas Southwestern Medical Center, Dallas; Martin Rudwaleit, MD, Joachim Sieper, MD: Charité Universitätsmedizin, Campus Benjamin Franklin, Berlin, Germany; Michael H. Weisman, MD: Cedars-Sinai Medical Center, Los Angeles, California; Robert B. M. Landewé, MD: Academic Medical Centre and University of Amsterdam, Amsterdam, The Netherlands. Dr. Deodhar has received consulting fees, speaking fees, and/or honoraria from UCB, Novartis, AbbVie, Pfizer, and MSD (less than

Association study of genes related to bone formation and resorption and the extent of radiographic change in ankylosing spondylitis

10,000 each), has served as an expert witness on behalf of UCB and AbbVie, and has received research grants from UCB, AbbVie, Novartis, Pfizer, and Amgen. Dr. van den Bosch has received consulting fees, speaking fees, and/or honoraria from AbbVie, Celgene, MSD, Pfizer, and UCB (less than

MICA, a gene contributing strong susceptibility to ankylosing spondylitis

10,000 each). Dr. Braun has received consulting fees, speaking fees, and/or honoraria from AbbVie (Abbott), Amgen, Bristol-Myers Squibb, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Medac, MSD (ScheringPlough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, SanofiAventis, and UCB (less than

Recognition and treatment of juvenile-onset spondyloarthritis.

10,000 each). Dr. Burgos-Vargas has received consulting fees, speaking fees, and/or honoraria from AbbVie, Bristol-Myers Squibb, Janssen, Pfizer, Roche, and UCB (less than