Showing papers by "Nidhi Sofat published in 2022"

P31 Chicken or egg: Inflammatory bowel disease in ankylosing spondylitis

Abstract: 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. 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. 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. 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.

Tocilizumab for relapsing and remitting giant cell arteritis: a case series

Abstract: Giant cell arteritis is a large vessel vasculitis of the arteries in the head and neck. The mainstay of management is with high-dose corticosteroids, and patients often face difficulties stopping or reducing steroids without recurrence of symptoms. Corticosteroids are well established to have numerous associated side effects, including osteoporosis, weight gain, and diabetes. Therefore, when tocilizumab was approved for up to 1 year for cases of relapsing or refractory giant cell arteritis by the National Institute of Health and Care Excellence (NICE) in April 2018, this offered an opportunity to benefit from new funding and to reduce steroid burden.This case series describes the impact of the establishment of a new hub and spoke referral pathway for the use of tocilizumab in refractory or relapsing giant cell arteritis, with case examples from consecutive patients who accessed the funding between August 2018 and April 2021. A total of 16 patients were identified: 11 female and 5 male, with an average age of 72.4 (range 61-82) years, with a majority of 11 ethnically white. The central assessing hub is St George's University Hospitals NHS Foundation Trust Hospital, serving a population of 1.3 million in the south of England. This is the first large case series looking into the impact of the establishment of a regional clinical pathway for the new tocilizumab funding.The case series demonstrates that the use of tocilizumab has reduced both the duration and the dose of corticosteroids in these 16 cases (mean prednisolone reduction 20.4 mg: 95% CI 13.0-27.8 mg), with 50% of patients continuing on tocilizumab after the initial 12 month funding period. The disease course, patterns of response, and maintenance of remission are discussed, and we describe the benefits of replicating this hub and spoke tocilizumab pathway in other centers.

P46 A rare case of costovertebral arthritis in SLE

Abstract: Abstract Introduction/Background Systemic Lupus Erythematosus (SLE) is a chronic, multi-system, autoimmune condition with a waxing and waning course affecting joints, skin, hair, heart, lungs and kidneys.The atypical activation of native immunity in SLE causing immune complexes deposition throughout the body directly induces inflammation and tissue damage. SLE arthritis usually follows non-erosive pattern. The costovertebral joints are affected when there is mechanical irritation between the spinal curve at T6-T8 and oblique and twisting ribs, causing localised and referred pain to chest and abdomen when intercostal nerves are involved. We present an unusual case of chronic back pain from thoracic costovertebral arthritis secondary to SLE. Description/Method This 32-year-old black woman presented to rheumatology seven years ago, with a few years’ history of alopecia, mouth ulcers, mid-thoracic back pain, intermittent chest pain, migrating polyarthralgia and fatigue on a background of Raynaud’s phenomenon, migraine, seborrheic dermatitis, and depression. Her back pain started ten to fifteen years ago. The pain was focused on the posterior left mid thoracic region with varying intensity. It persisted throughout the day and often radiated to her anterior chest wall. The pain was aggravated by climbing stairs and other activities requiring respiratory effort. Her initial autoimmune blood results showed a strongly positive ANA and positive Anti-Ro levels, favouring the diagnosis of SLE and Sjogren’s syndrome. She had a negative dsDNA antibody, crythidia antibody, rheumatoid factor, and normal complement levels. She was started on Hydroxychloroquine and Non-steroidal Anti-inflammatory drugs (NSAIDS). Later on, Mycophenolate Mofetil was added following disease flare. In the last seven years, she presented with back pain and chest pain multiple times to her primary health physician and emergency, where the diagnosis was put down to mechanical back pain and costochondritis. She was also extensively investigated by cardiology previously, for serositis with an echocardiogram, 24-hour Holter tape and cardiac MRI, all of which were normal. Later, it was thought that her symptoms were secondary to fibromyalgia and was referred to a pain specialist and for local steroid injection, which yielded no benefit. A further rheumatology review helped to re-evaluate the clinical condition, indicating tenderness over left T4 and T5 paraspinal region along with left anterior rib margin tenderness. Further CT and MRI imaging, specialist musculoskeletal radiologist review and multidisciplinary team input revealed costovertebral arthritis secondary to lupus causing back pain and referred pain to chest wall. She has been referred for a focused steroid injection along with physiotherapy. Discussion/Results The prevalence of chronic back pain is around 40% in the United Kingdom. Thoracic involvement is more frequently seen with SLE than any other autoimmune disease. This interesting case of chronic back pain with referred pain has a wide array of differentials and a rare finding, especially with a diagnosis of SLE. Normal chest x-ray, cardiac investigations, inflammatory markers, chronicity, and lack of infective symptoms ruled out metabolic, cardiac, and infective causes Costovertebral and costotransverse arthritis are often associated with ankylosing spondylitis and osteoarthritis but very rarely with lupus and is an uncommon cause of thoracic backache. Fibrositis causing back pain and referred pain has more association with lupus and is seen in around 20% of SLE patients. CT scan showed a focal soft tissue swelling in the left T8 and T9 posterior intercostal space involving the adjacent costovertebral and costotransverse joints, associated with left T8 costotransverse joint marrow signal abnormality and joint oedema. Her T1 weighted MRI and Short Tau Inversion Recovery (STIR) imaging confirmed the fat density, diffuse oedema seen with in the soft tissue mass. Her MRI was compared to previous imaging done a few years ago and interestingly showed focal swelling, oedema, and marrow signal change. The fat swelling and oedema progressed little over time, but the marrow signal change appeared less intense on the recent MRI. The MRI also demonstrated the undistorted, uninvaded course of nerves and bloods vessels clean through the focal structure ruling out a tumour. Absence of bony spur and enthesitis ruled out ankylosing spondylitis. The absence of neurological symptoms and radiological evidence also ruled out myelitis. The detection of bone marrow oedema by MRI can be considered as a valuable tool for defining the severity and extent of inflammatory processes in chronic joint disease. Key learning points/Conclusion This rare case cites the importance of exploring pathophysiology of chronic back pain especially in a multisystem disease like SLE. The musculoskeletal structures of the thoracic wall and the neck are a relatively common source of back pain as well as chest pain. This case helped to reinforce the fundamentals of clinical practice, careful analysis of the history, physical findings and radiological investigations are essential for precise diagnosis and effective treatment. Also, the knowledge of the anatomic structures and thorough evaluation of the ribs, intercostal spaces, muscles, sternum, sternoclavicular joints, and cervical and thoracic spine is essential for understanding the pathophysiology of referred pain. The full facet joints T1(first thoracic vertebrae), T11 and T12 joints have high frequency for arthritis due to the absence of intervertebral discs. The peak of the spinal curve at T6-T8 corresponds to the level of oblique and twisting ribs causing more mechanical irritation between the vertebra and the ribs, leading to changes in the costovertebral joints. From a clinical perspective, patients would experience pain and local tenderness near the vertebral column aggravated by coughing and respiratory movements. The close relationship with intercostal nerves can trigger referred pain to the chest or abdomen. This case also highlights the importance of CT and MRI imaging to establish the cause and offer effective treatment. Refractory cases of costovertebral arthritis often need local steroid injection for symptom management, biologics and rarely need resection arthroplasty. Nonetheless, the MDT approach is often valuable in favouring a conclusive diagnosis and focused treatment plan. From the literature search we have performed, this is one of the few such reported cases. Failure to appreciate such a diagnosis could lead to continuity of symptoms, deterioration in mobility and quality of life.

What is the full potential of baricitinib in treating patients with COVID-19?

Abstract: This has been removed as per the suggestions from the editorsEditorial.

P193 How did people with rheumatoid arthritis experience the COVID-19 pandemic? Interim qualitative results from the BIORA-PAIN study

Abstract: Abstract Background/Aims Over the last 12 months (September 2020-21), we have been conducting a clinical trial with two biologic agents comparing pain outcomes in rheumatoid arthritis (RA) (n = 26). Within the trial, we investigated how participants with RA taking immunosuppressive medication felt about their care and responded to the COVID-19 pandemic. Such information is important to guide healthcare providers. Methods Semi-structured interviews were conducted either face-to-face or virtually with participants who had recently been recruited to the Biologics for Rheumatoid Arthritis Pain (BIORA-PAIN) study and attended a South West London hospital. Participants had a DAS-28-CRP score of above 5.1 and were just starting on biological treatment. Seven interviews were conducted between April-September 2021, lasting between 23-60 minutes during which participants were asked how they managed their RA during the pandemic. All the responding participants were female, aged between 27-74 (mean 50.3 years), with a mixture of employment status and some living alone or with others. Interviews were recorded then transcribed verbatim and an interim thematic analysis was conducted. Results Four main themes were identified: the effect of lockdown; care of self; medical care; and support. Participants reported weight gain during lockdown due to being more sedentary and feeling less able to exercise, which increased stiffness. Despite reporting no official advice from doctors regarding shielding, most participants felt more vulnerable due to awareness of immunosuppression, but protective measures and vaccine uptake alleviated fears. Many sought advice from online resources, such as Versus Arthritis, and support groups which, as well as comfort, provided information enabling some participants to ask doctors specific questions about their care and medications. Most participants were wary of misinformation and chose to use trusted websites such as NHS and gov.uk or sources advised by doctors. There were varied reports of participants’ experiences of their care: most participants felt that their care was largely unaffected by the pandemic, with all participants feeling able to obtain current medication. However, some felt the COVID-19 restrictions slowed the progress of their care and felt unsupported whilst suffering worsening symptoms. Face-to-face appointments were preferred over telephone appointments, as participants felt doctors were unable to assess their pain and joints via phone call. Participants who lived alone suffered more mentally. Conclusion Participants in this study were wary of coronavirus in relation to their disease and many chose to shield whilst reporting no shielding guidance. Many participants looked for reliable sources to research their care and treatment, which have been increased by feeling less able to contact clinicians during the pandemic. Participants felt that routine treatment was possible via telephone but changes in their condition required face-to-face appointments. Disclosure A. Blundell: None. G. Mein: None. S. Koushesh: None. A. Omoruyi: None. A. Harrison: None. P. Sedgwick: None. N. Sofat: None.

JAK Inhibitors in Rheumatoid Arthritis

Abstract: JAK inhibitors (JAKi) are targeted, small-molecule, disease-modifying therapies that are the newest class of treatments to emerge for the management of rheumatoid arthritis (RA) and the first oral disease-modifying anti-rheumatic drugs (DMARD) to demonstrate comparable clinical efficacy to biological DMARDs (bDMARD). In the UK there are four JAKi licensed for the treatment of RA (baricitinib, tofacitinib, upadacitinib, and filgotinib) and recent years have seen an explosion in their use. Clinical trial evidence supports their efficacy in a range of RA cohorts including DMARD-naïve patients and those with treatment-refractory disease. JAKi are associated with increased risk for infection, particularly herpes zoster virus reactivation, cytopenias, and hyperlipidaemia. In older patients with cardiovascular risk factors, post-marketing data suggest increased risk for malignancy, venous thromboembolism (VTE), and major cardiovascular events (MACE) with JAKi. This review article discusses the mechanism of action of JAKi and the evidence for their efficacy and side effect profile.