Association of Inflammatory Bowel Disease and Acute Anterior Uveitis, but Not Psoriasis, With Disease Duration in Patients With Axial Spondyloarthritis

Varkas, Gaëlle; Vastesaeger, Nathan; Cypers, Heleen; Colman, Roos; Renson, Thomas; Praet, Liesbet Van; Carron, Philippe; Raeman, F.; Devinck, Mieke; Gyselbrecht, Lieve; Corluy, L; Piette, Yves; Lenaerts, Jan; Thevissen, Kristof; Vanneuville, B.; Bosch, Filip Van den; Elewaut, Dirk

doi:10.1002/art.40551

Cited by 36 publications

(20 citation statements)

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“…This is consistent with previous reports 7 17 and offers a potential strategy for targeted identification of people with AAU in ophthalmology clinics who may have underlying axSpA. 18– 20 Interestingly, participants with IBD and psoriasis had lower rates of HLA-B27 positivity than the overall cohort and both had negative associations with HLA-B27 status, consistent with results from a recent study by Varkas et al 21 This may indicate that people with psoriasis or IBD and back pain are more likely to be diagnosed with axSpA, regardless of their HLA-B27 status. Interestingly, a positive HLA-B27 (plus at least two other SpA features, which could include psoriasis or IBD) is required to fulfil the clinical arm of the ASAS classification criteria for axSpA 10 ; this may suggest that these participants are more likely to fulfil the imaging arm (HLA-B27 not required).…”

Section: Discussionsupporting

confidence: 91%

Predictors of extra-articular manifestations in axial spondyloarthritis and their influence on TNF-inhibitor prescribing patterns: results from the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis

et al. 2020

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ObjectivesExtra-articular manifestations (EAMs) are important systemic features of axial spondyloarthritis (axSpA), which may influence the choice of tumour necrosis factor-inhibitor (TNFi). We examined the cumulative incidence and predictors of EAMs and the influence of these on first TNFi choice in a ‘real-world’ cohort of patients with axSpA.MethodsClinical and patient-reported outcomes of 2420 patients with axSpA from 83 centres were collected by the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis. Lifestyle factors for EAMs (acute anterior uveitis (AAU), inflammatory bowel diseases (IBD), psoriasis) were compared with those without EAMs. Also, the association between pretreatment EAMs and choice of first TNFi (adalimumab, etanercept, certolizumab) was analysed.ResultsAAU was directly associated with human leukocyte antigen (HLA)-B27 (incidence rate ratio (IRR) 1.95, 95% CI 1.40 to 2.73) and inversely associated with ever-smoking (IRR=0.71, 95% CI 0.55 to 0.92). For both psoriasis and IBD, there was an inverse relationship with HLA-B27 (IRR 0.54, 95% CI 0.36 to 0.79 and IRR 0.63, 95% CI 0.43 to 0.91, respectively). A diagnosis of either AAU (OR 3.79, 95% CI 2.11 to 6.80) or IBD (OR 5.50, 95% CI 2.09 to 14.46) was associated with preference for adalimumab versus others. In contrast, a diagnosis of either AAU (OR 0.14, 95% CI 0.06 to 0.33) or IBD (OR 0.17, 95% CI 0.05 to 0.57) was associated with less preference for etanercept over other TNFi.ConclusionThe higher occurrence of AAU and lower occurrence of psoriasis and IBD in HLA-B27-positive patients with axSpA are consistent with current pathophysiology. Patients with previous AAU and IBD are more likely to be prescribed adalimumab and less likely to receive etanercept, consistent with the superior efficacy of monoclonal TNFi for these indications. Future work will determine whether EAMs influence TNFi survival, or effectiveness, and whether this varies between agents.

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Section: Discussionsupporting

confidence: 91%

Predictors of extra-articular manifestations in axial spondyloarthritis and their influence on TNF-inhibitor prescribing patterns: results from the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis

et al. 2020

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“…The incidences of IBD and acute anterior uveitis in the current study involving patients with prior inadequate response to or intolerance of 1 or 2 TNFi, and longstanding (mean ± SD symptom duration 18.4 ± 11.1 years) and very active disease, were higher than reported among bDMARD‐naive patients with radiographic axial SpA treated with ixekizumab . Certain comorbidities in axial SpA, especially IBD and acute anterior uveitis, have been reported to be associated with longer disease duration . Integrated data from the ixekizumab axial SpA studies, as well as longer‐term data, are needed to better understand whether the IBD events observed in the current study reflect the recruited patient population, study treatment, other factors (such as discontinuation of prior TNFi), or a combination of the above .…”

Section: Discussionmentioning

confidence: 96%

Efficacy and Safety of Ixekizumab in the Treatment of Radiographic Axial Spondyloarthritis: Sixteen‐Week Results From a Phase III Randomized, Double‐Blind, Placebo‐Controlled Trial in Patients With Prior Inadequate Response to or Intolerance of Tumor Necrosis Factor Inhibitors

Deodhar

Poddubnyy

Pacheco‐Tena

et al. 2019

Arthritis & Rheumatology

168

179

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Objective To investigate the efficacy and safety of ixekizumab in patients with active radiographic axial spondyloarthritis (SpA) and prior inadequate response to or intolerance of 1 or 2 tumor necrosis factor inhibitors ( TNF i). Methods In this phase III randomized, double‐blind, placebo‐controlled trial, adult patients with an inadequate response to or intolerance of 1 or 2 TNF i and an established diagnosis of axial SpA (according to the Assessment of SpondyloArthritis international Society [ ASAS ] criteria for radiographic axial SpA, with radiographic sacroiliitis defined according to the modified New York criteria and ≥1 feature of SpA) were recruited and randomized 1:1:1 to receive placebo or 80‐mg subcutaneous ixekizumab every 2 weeks ( IXE Q2W) or 4 weeks ( IXEQ4W ), with an 80‐mg or 160‐mg starting dose. The primary end point was 40% improvement in disease activity according to the ASAS criteria ( ASAS 40) at week 16. Secondary outcomes and safety were also assessed. Results A total of 316 patients were randomized to receive placebo (n = 104), IXEQ2W (n = 98), or IXEQ4W (n = 114). At week 16, significantly higher proportions of IXEQ2W patients (n = 30 [30.6%]; P = 0.003) or IXEQ4W patients (n = 29 [25.4%]; P = 0.017) had achieved an ASAS 40 response versus the placebo group (n = 13 [12.5%]), with statistically significant differences reported as early as week 1 with ixekizumab treatment. Statistically significant improvements in disease activity, function, quality of life, and spinal magnetic resonance imaging–evident inflammation were observed after 16 weeks of ixekizumab treatment versus placebo. Treatment‐emergent adverse events ( AE s) with ixekizumab treatment were more frequent than with placebo. Serious AE s were similar across treatment arms. One death was reported ( IXEQ2W group). Conclusion Ixekizumab treatment for 16 weeks in patients with active radiographic axial SpA and previous inadequate response to or intolerance of 1 or 2 TNF i yields rapid and significant improvements in the signs and symptoms of radiographic axial SpA versus placebo.

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“…It seems that some comorbidities, like IBD and anterior uveitis, could be associated with longer disease duration. 49 In many cases, patients had a pre-existing history of anterior uveitis and were HLA B27+ 45 About malignancies, there was only one case of acute promyelocytic leukemia (PML) few weeks after IXE started in a patient with genetic predisposition in COAST-W 45 and a bladder cancer in COAST-V LTE. 46 About cerebrocardiovascular events, there was one case of atrial fibrillation in IXE q2W group in COAST-W, 45 two cases of cerebrocardiovascular events in COAST-V ETP 46 and one major cardiovascular event (acute myocardial infarction) in COAST-W ETP.…”

Section: Safety Of Ixekizumab In Asmentioning

confidence: 99%

<p>Therapeutic Potential of Ixekizumab in the Treatment of Ankylosing Spondylitis: A Review on the Emerging Clinical Data</p>

Benucci

Damiani

Gobbi

et al. 2020

TCRM

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Over the last 20 years, the greatly improved knowledges of underlying pathogenic mechanisms of AS, including the role of tumor necrosis factor (TNF), the interleukin 23/Th17 axis, and interleukin-17 (Il-17), constituted the rationale to develop biologics selectively inhibiting these pathways. For more than 10 years, anti-TNF biologics were successfully employed to treat AS, with marked improvement of signs and symptoms in around 60% of the patients. Recent knowledge of the pathophysiology of spondyloarthritis has highlighted the emerging role of the IL-17/IL-23 axis. New therapies with selective biological drugs have emerged in the treatment of this pathology. In this review, we evaluated the effects of ixekizumab, a new anti-IL-17A, that was licensed both by EMA and FDA in August 2019 for the treatment of ankylosing spondylitis. The review highlights the efficacy and safety data of the 3 randomized controlled trials (COAST V-COAST W-COAST X) and those of the extension to 52 weeks of COAST V and COAST W.

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Association of Inflammatory Bowel Disease and Acute Anterior Uveitis, but Not Psoriasis, With Disease Duration in Patients With Axial Spondyloarthritis

Cited by 36 publications

References 36 publications

Predictors of extra-articular manifestations in axial spondyloarthritis and their influence on TNF-inhibitor prescribing patterns: results from the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis

Predictors of extra-articular manifestations in axial spondyloarthritis and their influence on TNF-inhibitor prescribing patterns: results from the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis

Efficacy and Safety of Ixekizumab in the Treatment of Radiographic Axial Spondyloarthritis: Sixteen‐Week Results From a Phase III Randomized, Double‐Blind, Placebo‐Controlled Trial in Patients With Prior Inadequate Response to or Intolerance of Tumor Necrosis Factor Inhibitors

<p>Therapeutic Potential of Ixekizumab in the Treatment of Ankylosing Spondylitis: A Review on the Emerging Clinical Data</p>

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