P31 Chicken or egg: Inflammatory bowel disease in ankylosing spondylitis
Authors: Biddle Kathryn , Sofat Nidhi 
Published: September 2022

Abstract

Introduction/Background
Inflammatory bowel disease (IBD) is an important extra-articular manifestation of spondyloarthritis (SpA) and has significant implications on patient quality of life and rheumatological management. We report a case of severe Crohn’s disease in a patient with axial spondyloarthritis (AxSpA) and secondary non-response to Tumour Necrosis Factor inhibition (TNFi). We will focus on the rationale for treatment decisions and the important factors to consider in patients with co-existent IBD and SpA.

Description/Method
A 34-year-old Caucasian gentleman presented to the emergency department (ED) with a 3-week history of diarrhoea and abdominal pain. He had a background of AxSpA which was diagnosed three years previously following referral to rheumatology clinic. At diagnosis, he reported cervical and lumbar back pain and previous Achilles tendonitis. MRI showed bilateral sacroiliitis and thoracolumbar Romanus lesions. HLA-B27 was negative. Naproxen and adalimumab resulted in a significant initial improvement in symptoms however following 18 months of therapy (with which the patient was compliant), he noted worsening pain and stiffness affecting his right hip, cervical spine and sacroiliac joints.
On ED assessment, the patient reported upper abdominal pain and four-to-five episodes of loose, watery stools per day. His CRP was 45mg/L and a CT abdomen-pelvis showed oedema and mucosal enhancement of the distal ileum, an inflammatory phlegmon in the right iliac fossa and low-grade obstruction of the small bowel. Features were suggestive of active Crohn’s disease (CD). The patient was admitted under the gastroenterology team and commenced on intravenous antibiotics and exclusive enteral nutrition (EEN). After two days of inpatient treatment, he was discharged.
The patient was discussed in the gastroenterology biologics meeting. Bloods showed subtherapeutic adalimumab levels with positive anti-drug antibodies (ADA). He was therefore switched to infliximab in combination with methotrexate. Shortly after receiving his first dose of infliximab, he represented to hospital with ongoing right iliac fossa pain and low-grade fevers. His CRP was 77mg/L and a CT abdomen-pelvis showed persistence of the inflammatory phlegmon and distal ileitis. During a second five-day inpatient admission, he received two further doses of infliximab and a 10-day course of antibiotics. Following discharge, he received a fourth dose of infliximab and is clinically improving with resolving abdominal symptoms, inflammatory markers and joint pain.

Discussion/Results
SpA and IBD are auto-inflammatory conditions with epidemiological, genetic and pathological links. Patients with SpA have a 4-14% lifetime risk of IBD and a 60% prevalence of subclinical gut inflammation. IBD can precede, develop in synchrony or follow the onset of joint symptoms with increased risk in patients with higher disease activity. Dysregulated type 3 immunity is implicated in both conditions however the pathological link between gut and joint inflammation is poorly understood. Furthermore, important differences in immunopathogenesis exist with notable implications for biological treatments, for example IL-17 inhibition is an effective treatment for AxSpA but worsens IBD.
This case highlights some of the differences in the immunomodulatory and biological treatment of AxSpA and IBD. In CD, methotrexate is commonly used to maintain remission. This contrasts to the guidance for AxSpA where the use of conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) is not recommended. As illustrated in this case, TNFi are used in the treatment of both AxSpA and IBD however infliximab dosing in IBD is conventionally higher with doses of 5mg/kg given at weeks 0, 2, 6 and then 8-weekly.
In this case, the patient developed secondary non-response to TNFi due to the presence of functional ADA. ADA are associated with lower serum drug levels, loss of therapeutic response, infusion reactions and discontinuation of TNFi. In some case series, ADA are present in 15-30% of patients on adalimumab. Co-prescription of immunomodulatory therapies are associated with improved pharmacokinetics of TNFi, lower risk of ADA and reduced risk for treatment failure. This is particularly important when switching between TNFis when there is increased risk of ADA with second-line TNFi agents. As illustrated in this case, gastroenterology guidelines recommend the measurement of adalimumab levels and ADA to guide treatment decisions. This is an area in rheumatological practice where consensus is required.

Key learning points/Conclusion
1. IBD is an important extra-articular manifestation of SpA that rheumatologists should be alert for. The link between joint and gut inflammation in SpA is an area of ongoing research and has important treatment implications for patients with co-existent disease. When IBD is present, the choice of disease modifying therapy can differ.
2. TNFi are used in the management of both CD and AxSpA however there are differences in dose selection and dose titration between the two conditions. Higher doses are typically used in IBD.
3. In patients with secondary non-response to TNFi, the British Society for Gastroenterology (BSG) guidelines suggest measurement of drug levels and ADAs to guide further management. In patients with adequate drug concentration or positive ADAs, the BSG guidelines suggest switching to an alternative TNFi or alternative class. In inflammatory rheumatic disease, clear clinical guidance does not yet exist despite a growing body of evidence supporting the use of therapeutic drug monitoring in some scenarios.
4. In patients with CD who formed ADA against one TNFi, gastroenterology guidelines recommend the co-prescription of an immunomodulatory medication to reduce the risk of non-response to a second TNFi. Current rheumatology guidelines do not advocate this approach and this is an area of uncertainty in the management of AxSpA patients.
5. In all cases of co-existent IBD and SpA, close collaboration between rheumatology and gastroenterology colleagues is of upmost importance.