O03 Continuation of golimumab (anti-TNF) in a patient with SpA and low-risk prostate cancer, what is the right decision?

Abstract Case report - Introduction Golimumab is an anti-TNF alpha drug used in the treatment of inflammatory arthritis including spondyloarthritis (SpA). The introduction of this drug class has revolutionised the treatment of SpA over the last 20 years with significantly improved patient outcomes. Despite their treatment benefits multiple adverse effects of TNF-alpha inhibition have been reported through clinical trials including a possible increased risk of malignancy. We describe a case of a patient with known ankylosing spondylitis (AS) on golimumab who was diagnosed with low-grade prostate carcinoma and discuss the factors taken into consideration in guiding our decision-making process regarding ongoing treatment. Case report - Case description A 57-year-old gentleman with known AS presented to the rheumatology clinic for routine review. His AS was well controlled, and he had been taking golimumab for the past 3 years. Upon review he was in clinical remission with a CRP <1 and ESR 5. Prior to the initiation of anti-TNF therapy his disease had been poorly controlled. However, following commencement his symptoms had significantly improved and he was able to work as a professional sports coach whilst bringing up a young family. On review he had recently been diagnosed with low-risk cancer of the prostate by his urologist. A prostate biopsy found Gleason 3 + 3 adenocarcinoma involving 2 out of 22 cores on each side, with a prostate specific antigen (PSA) of 3.95ng/ml. An MRI had shown chronic prostatitis. He was in the lowest risk category of grade group 1 prostate cancer and no treatment for his prostate cancer was indicated. The plan from his urology team was active surveillance with PSA monitoring. Whilst being investigated for possible malignancy his golimumab had been held for six months and during this period he had a significant flare in symptoms. He experienced severe back pain that forced him to stop working. Following his prostate cancer diagnosis, golimumab was restarted by his urologist with a subsequent improvement in his AS symptoms. To guide ongoing treatment his case was reviewed in the local biologics multi-disciplinary team meeting, alongside close communication with his urologist. The patient was informed of the risks of continuing golimumab in relation to his malignancy. Despite this he was reluctant to stop anti-TNF therapy or switch to another treatment, citing concerns about the impact it might have on his symptoms and ability to work. Case report - Discussion  This case highlights the complexities involved in the management of a patient on anti-TNF therapy, who receives a diagnosis of malignancy, particularly when the diagnosis is classed as low risk. Traditionally anti-TNF therapy was contraindicated for patients with a history of a solid organ tumour within the previous five years. The British Society of Rheumatology (BSR) guidelines recommends that patients should be advised that there is no conclusive evidence for an increased risk of solid organ tumours but that on-going vigilance is required. A holistic patient-centred approach needs to be taken in these contexts, and consideration of cases on an individual basis is needed. Inter-disciplinary and multi-speciality team input, with the effective use of a biologics MDT, is crucial. The patient was understandably reluctant to stop his treatment due to the significant impact this may have on his quality of life. On liaison with his urologist his prostate cancer was in the lowest risk category with 99% 5-year survival rates with low risk of disease progression or spread. Evidence in this field to date has been conflicting and studies have predominantly focused on the safety of anti-TNFs in rheumatoid arthritis patients. Recent large national registry data has been reassuring. Few studies have looked at the AS and psoriatic arthritis anti-TNF treated population; however, a meta-analysis of RCTs found no evidence of increased incidence of malignancy. Taking into account his low-risk cancer, the patient’s wishes and clinical evidence in this field we have made to decision to continue anti-TNF treatment for now but with ongoing surveillance for any tumour progression. The patient will undergo urology follow up alongside regular PSA monitoring, and there will be a low threshold to stop or switch treatment in the future Case report - Key learning points Treatment with anti-TNF therapy in patients with concomitant inflammatory arthritis and malignancy pose a specific challenge that require close co-ordination of care between rheumatologists, oncologists, other relevant teams and may benefit from the use of local biologics MDT to guide ongoing drug therapy. It is important to take a patient centred approach and consider cases on an individual basis taking into account their cancer diagnosis, extent of disease, histology findings and their response to TNF treatment. Patients must always be counselled on the risk of continuing anti-TNF and be involved in the decision-making process. Further research is required to look at the safety of anti-TNF particularly in SpA and if there is an increased risk of malignancy.

. Primary peritoneal cancer is uncommon and can present as an incidental finding . Whilst treatment for progressive cancer is important, withholding rheumatoid arthritis treatment can have a significant adverse impact on quality of life . Morbidity and mortality risks of stopping treatment versus combined treatment (cancer therapy and disease-modifying therapy) ideally needs to be fully discussed and agreed with the patient and all care providers -lack of "named" providers, restructuring, redeployment, multi-specialty care and a global pandemic can make coordination of this difficult Case report -Introduction: Golimumab is an anti-TNF alpha drug used in the treatment of inflammatory arthritis including spondyloarthritis (SpA). The introduction of this drug class has revolutionised the treatment of SpA over the last 20 years with significantly improved patient outcomes. Despite their treatment benefits multiple adverse effects of TNF-alpha inhibition have been reported through clinical trials including a possible increased risk of malignancy. We describe a case of a patient with known ankylosing spondylitis (AS) on golimumab who was diagnosed with low-grade prostate carcinoma and discuss the factors taken into consideration in guiding our decision-making process regarding ongoing treatment.
Case report -Case description: A 57-year-old gentleman with known AS presented to the rheumatology clinic for routine review. His AS was well controlled, and he had been taking golimumab for the past 3 years. Upon review he was in clinical remission with a CRP <1 and ESR 5.
Prior to the initiation of anti-TNF therapy his disease had been poorly controlled. However, following commencement his symptoms had significantly improved and he was able to work as a professional sports coach whilst bringing up a young family. On review he had recently been diagnosed with low-risk cancer of the prostate by his urologist. A prostate biopsy found Gleason 3 þ 3 adenocarcinoma involving 2 out of 22 cores on each side, with a prostate specific antigen (PSA) of 3.95ng/ml. An MRI had shown chronic prostatitis. He was in the lowest risk category of grade group 1 prostate cancer and no treatment for his prostate cancer was indicated. The plan from his urology team was active surveillance with PSA monitoring. Whilst being investigated for possible malignancy his golimumab had been held for six months and during this period he had a significant flare in symptoms. He experienced severe back pain that forced him to stop working. Following his prostate cancer diagnosis, golimumab was restarted by his urologist with a subsequent improvement in his AS symptoms.
To guide ongoing treatment his case was reviewed in the local biologics multi-disciplinary team meeting, alongside close communication with his urologist. The patient was informed of the risks of continuing golimumab in relation to his malignancy. Despite this he was reluctant to stop anti-TNF therapy or switch to another treatment, citing concerns about the impact it might have on his symptoms and ability to work. Case report -Discussion : This case highlights the complexities involved in the management of a patient on anti-TNF therapy, who receives a diagnosis of malignancy, particularly when the diagnosis is classed as low risk. Traditionally anti-TNF therapy was contraindicated for patients with a history of a solid organ tumour within the previous five years. The British Society of Rheumatology (BSR) guidelines recommends that patients should be advised that there is no conclusive evidence for an increased risk of solid organ tumours but that on-going vigilance is required. A holistic patient-centred approach needs to be taken in these contexts, and consideration of cases on an individual basis is needed.
Inter-disciplinary and multi-speciality team input, with the effective use of a biologics MDT, is crucial. The patient was understandably reluctant to stop his treatment due to the significant impact this may have on his quality of life. On liaison with his urologist his prostate cancer was in the lowest risk category with 99% 5-year survival rates with low risk of disease progression or spread. Evidence in this field to date has been conflicting and studies have predominantly focused on the safety of anti-TNFs in rheumatoid arthritis patients. Recent large national registry data has been reassuring. Few studies have looked at the AS and psoriatic arthritis anti-TNF treated population; however, a meta-analysis of RCTs found no evidence of increased incidence of malignancy. Taking into account his low-risk cancer, the patient's wishes and clinical evidence in this field we have made to decision to continue anti-TNF treatment for now but with ongoing surveillance for any tumour progression. The patient will undergo urology follow up alongside regular PSA monitoring, and there will be a low threshold to stop or switch treatment in the future Case report -Key learning points: 1. Treatment with anti-TNF therapy in patients with concomitant inflammatory arthritis and malignancy pose a specific challenge that require close co-ordination of care between rheumatologists, Case report -Introduction: Rheumatoid Arthritis is associated with an increased risk of lymphoma. The relative contribution of cumulative disease activity versus immunosuppressive treatments, in particular anti-TNF, to the overall risk remains controversial. Awareness of this complication is important as most such lymphomas are highly treatment-sensitive when diagnosed early.
We report a case of orbital mucosa-associated lymphoid tissue (MALT) lymphoma in a patient with established rheumatoid arthritis with secondary Sjogren's syndrome with quiescent disease treated with methotrexate and etanercept for many years. We discuss the risk factors, clinical signs and rationale for subsequent treatment decisions, including consideration of rituximab to treat both conditions. Case report -Case description: A 72-year-old lady with longstanding rheumatoid arthritis and secondary Sjogren's reported a 1-year history of unilateral painless left watering eye and lid swelling. Vision was unaffected. There was no systemic upset or B-symptoms. Her rheumatoid arthritis was quiescent on methotrexate and etanercept. Past medical history consisted of asthma, hiatus hernia, subtalar arthrodesis and granuloma annulare. Other medications included folate, naproxen, lansoprazole, rosuvastatin and salbutamol and beclomethasone inhalers. She was a current smoker with a 40 pack-year history. On examination, there was a palpable mass on the nasal aspect of her left upper eyelid. Ocular examination was otherwise unremarkable and she had no lymphadenopathy. Inflammatory markers were normal: CRP 2 mg/L and ESR 28 mm/hr with unremarkable full blood count, urea and electrolytes and liver function tests. LDH of 252 IU/L was at the upper limit of normal. Gadolinium-enhanced MRI revealed a 38mm x 20mm x 8mm soft tissue mass within the extraconal compartment of the left orbit, raising the possibility of lymphoma. CT chest, abdomen and pelvis showed no distant metastases. Orbital biopsy revealed evidence of a kapparestricted low-grade B-cell lymphoma with morphology and immunophenotype in keeping with MALT lymphoma. The MDT decision was to actively monitor with interval re-imaging. Etanercept and low-dose methotrexate were continued. Follow-up MRI at 4 months revealed near complete resolution of the left orbital mass. Her ocular symptoms had also spontaneously resolved. Etanercept was stopped at this time due to concerns around recent malignancy, with a plan to switch to rituximab. Her joints flared after stopping etanercept, but the first cycle of rituximab was very effective in controlling her arthritis. The patient is now awaiting a second cycle after a flare 9 months later. She has had no recurrence of ocular symptoms and remains under close and active surveillance for lymphoma. Case report -Discussion: This case illustrates the increased risk of non-Hodgkin's lymphoma in rheumatic disease, which may relate to impaired T-cell function in chronically active disease. MALT lymphomas account for around 8% of these; they originate from B cells and can affect nearly any mucosal site. Both chronic inflammation and immunosuppressive treatment contributed to increased risk here. Tumours are usually low-grade with onset in the 60s and 70s, with localised symptoms but minimal constitutional upset. Orbital MALT lymphomas present with a range of ocular symptoms; however, pain is rare and vision is usually preserved. There are no specific treatment guidelines; management is patient-specific and can include active monitoring, treating infection, immunotherapy, radiotherapy and chemotherapy. Prognosis of lymphoma associated with rheumatic disease is similar to the general population (<5% mortality if detected early). Evidence is conflicting as to whether anti-TNF agents increase the risk of lymphoma. Determining a causal link has proven difficult, due to the rarity of lymphoma and confounding factors, but mechanisms such as decreased activation of natural killer cells, a key defence against lymphoma, have been proposed. This contributed to the decision to stop etanercept in our patient. However, interestingly the lymphoma spontaneously resolved whilst the patient was still taking etanercept, which perhaps argues against the drug being a driving pathogenic factor. Another consideration in the decision to switch treatment was the potential overlapping benefit of rituximab. Cells of MALT lymphomas express CD20 antigen on their surfaces, and indeed this was observed in our patient's immunostaining. Such tumours are exquisitely sensitive to rituximab, and consequently it is often used first-line particularly in areas such as the orbit where radiotherapy can be problematic. It was therefore decided that rituximab would be the best treatment to optimise both conditions, despite there being no immediate need for immunological treatment of the lymphoma itself.
Case report -Key learning points: This case highlights the need to be aware of the increased risk of lymphoma in autoimmune rheumatic diseases such as rheumatoid arthritis and Sjogren's syndrome. The risk is elevated further in patients over 60 and those with chronically active disease. One must be vigilant during clinical assessment as patients often present with localised symptoms only, which could be dismissed as non-significant. In our case, signs and symptoms were limited to the left eye. Certainly, if any suspicious clinical features are detected, we advise a low threshold for prompt imaging studies followed by biopsy. Most such lymphomas are low-grade with effective treatment options, but do carry a small risk of high-grade transformation. Therefore, early recognition and treatment is vital and can be lifesaving.
Use of anti-TNF agents is recommended in patients with risk factors for developing lymphoma, especially given that cumulative inflammatory disease activity itself may represent a greater risk. Nevertheless, a low threshold of suspicion should be maintained. Based on uncertainties in the evidence, current expert consensus is to avoid anti-TNF agents in patients with current malignancy or any prior melanoma, and to exercise caution with a history of malignancy in the last 5 years. The safest course of action after a diagnosis of lymphoma is to stop anti-TNF agents.
We suggest consideration of rituximab as a safe alternative biologic treatment, given its efficacy in both conditions. Here, it was rationalised that using rituximab to treat the patient's rheumatoid arthritis could have an added protective effect on her risk of lymphoma recurrence.
To investigate this theory further, an interesting opportunity for further work would be to observe a cohort of such patients and compare the lymphoma recurrence rates of those who continued anti-TNF treatment against those who switched to rituximab or stopped biologics altogether.

ORAL ABSTRACT PRESENTATIONSCANCER IN RHEUMATIC DISEASE O05 A CASE OF CANCER MIMICKING INFLAMMATORY ARTHRITIS
Qurat Ul Ain Amjad and Spencer Ellis Rheumatology, Lister Hospital, East and North Hertfordshire Trust, Stevenage, United Kingdom Case report -Introduction: Rheumatic disease occurring as a paraneoplastic manifestation such as dermatomyositis is well recognised, whilst the symptoms of cancer may frequently mimic the presentations of common rheumatic disorders. It is essential to recognise these differential diagnoses to avoid delay in the detection of malignancy.
We present an unusual case of rheumatoid arthritis where, conversely, the diagnosis of inflammatory arthritis was delayed due to the attribution of musculoskeletal symptoms to existing malignancy undergoing treatment. This case highlights the importance of careful history and examination. Cancer and inflammatory disorders may co-exist and delayed diagnosis of either condition can result in increased morbidity. Case report -Case description: A 65-year-old male presented to Ear, Nose and Throat (ENT) clinic with a facial lump in association with swelling in his throat, tongue and neck associated with a decrease in appetite and weight loss. He reported an active lifestyle, including mountain climbing until a month prior. He was a non-smoker with alcohol intake of less than 10units/week. Other medical history included osteoarthritis of his left knee which did not limit function. Imaging of the head and neck confirmed a mass in the oropharynx, tonsils, and tongue muscles. Subsequent biopsy revealed moderate to poorly differentiated squamous cell carcinoma (SCC) of the left tonsil. 11 months prior to this presentation, he had developed pain and swelling involving knees, shoulders, and small joints of hands. His mobility