Introduction: Cellular senescence is the irreversible growth arrest subsequent to oncogenic mutations, DNA damage, or metabolic insult. Senescence is associated with ageing and chronic age associated diseases such as cardiovascular disease and diabetes. The involvement of cellular senescence in acute kidney injury (AKI) and chronic kidney disease (CKD) is not fully understood. However, recent studies suggest that such patients have a higher-than-normal level of cellular senescence and accelerated ageing. Methods: This study aimed to discover key biomarkers of senescence in AKI and CKD patients compared to other chronic ageing diseases in controls using OLINK proteomics. Results: We show that senescence proteins CKAP4 (p-value < 0.0001) and PTX3 (p-value < 0.0001) are upregulated in AKI and CKD patients compared with controls with chronic diseases, suggesting the proteins may play a role in overall kidney disease development. Conclusions: CKAP4 was found to be differentially expressed in both AKI and CKD when compared to UHCs; hence, this biomarker could be a prognostic senescence biomarker of both AKI and CKD.
Abstract Background/Aims Since the COVID-19 outbreak the rheumatology community have been concerned about the risk of SARS-CoV-2 infection in patients prescribed immunosuppressing medications. Data suggests that patients receiving Rrtuximab are at increased risk of developing severe outcomes from COVID-19 (1). In our unit all patients receiving rituximab were selected to receive a targeted vaccination and booster programme with all patients receiving at least 2 vaccinations and up to 3 booster vaccinations. We studied the efficacy of the COVID-19 vaccines in rituximab patients, by checking the the Roche Elecsys Anti-SARS-CoV-2-S (Spike) IgG/IgM total antibody levels post vaccination. Our aim was to assess the vaccination response in patients receiving rituximab and to offer advice on continued shielding or alternatively passive immunization with tixagevimab/cilgavimab in those patients who did not mount a response. Methods Taking 39 patients currently on rituximab therapy, we measured Anti-SARS-CoV-2-S (Spike) antibody levels post vaccination. We recorded whether the test was positive or negative, and the numerical result. We recorded rituximab dates of administration and dates of vaccines. We also recorded diagnosis, co-prescribed DMARDs, immunoglobulin levels, white cell and lymphocyte counts. We took record of whether or not the patient subsequently contracted COVID-19, required a hospital admission, ICU or died. Results Of our 39 patients, 21 had Anti-SARS-CoV-2-S (Spike) antibody levels checked. Of these patients, 7 (33%) had a negative spike protein result. Of the patients with a positive result, 8 (38%) had an antibody level between 0-250U/ML, and only 6 (28.6%) had a level >250U/ML (The manufacturer advises that a level above 0.8U/ML is a positive result). Of patients with a negative result, 1 patient had received 3 vaccines, 5 patients had received 4, and 1 patient had 5. All of the patients had received a vaccine >4 weeks prior to receiving the drug. Two patients were co-prescribed Belimumab, 3 were co-prescribed low-dose methotrexate and 2 were not on additional disease modifying agents. The diagnoses of these patients were, 2 patients with SLE, 4 with SPRA, and 1 MPO Vasculitis. There were no significant findings in lymphocyte count, white cell count or immunoglobulin levels. Conclusion These findings suggest that our current COVID-19 vaccination and booster programme may not provide adequate response in patients receiving rituximab therapy. Despite this being a small cohort, these results show that 33% of patients have not mounted a vaccine response and this is concerning. We suggest that vaccine response should be checked in all patients receiving rituximab therapy and those patients who do not mount a vaccine response should be offered passive immunity and advised of possible additional risks regarding COVID-19 exposure. Disclosure S.K. Stewart: None. A. Pendleton: None.
Introduction: Enthesitis is a hallmark of psoriatic disease, but its clinical assessment is problematic in terms of diagnostic sensitivity and overlap with other comorbid conditions. Ultrasound is a useful tool that can give a more detailed assessment of enthesitis. Research demonstrates that those with persistent ultrasound entheseal disease are at risk of progressive articular damage. With limited data to guide choice between biologic therapy for psoriatic arthritis (PsA) patients, we wanted to assess the response of ultrasound-confirmed enthesitis to different forms of biologic therapies and study its utility in making more informed decisions. Methods: This was an open label observational study including patients aged ⩾18 years, who fulfil the classification criteria for PSA (CASPAR) and were due to commence on their first biologic therapy. The primary outcome was the change in MAdrid Sonographic Enthesitis Index (MASEI) score at 16 weeks of treatment. The MASEI score was also modified to assess the active elementary lesions (ActiveMASEI). Results: In all, 80 PsA patients were enrolled with 75 patients completing the study [secukinumab n = 23 and tumour necrosis factor inhibitor (TNFi) n = 52]. The mean reduction in MASEI score after 16 weeks of treatment was 3.42 with TNFi versus 1.74 with secukinumab ( p = 0.097). There was a significant difference in the change in the MASEIActive score for TNFi versus secukinumab (4.37 versus 2.26; p = 0.030) and this difference was more pronounced when only power Doppler signal within 2 mm of the enthesis insertion was included (4.37 versus 2.00; p = 0.007). Clinical outcomes were similar for both classes of biologic apart from a significant reduction in regards to the Dermatology Life Quality Index and Psoriasis Area and Severity Index score with secukinumab versus TNFi. Conclusions: We have for the first time compared the effect of ultrasound-confirmed enthesitis between different forms of biologic therapies for PsA. We have seen an overall improvement in entheseal scores for both classes of medications and demonstrated a larger reduction in active entheseal disease for TNFi versus secukinumab that merits further exploration. Keywords biologic therapy , enthesitis , psoriasis , psoriatic arthritis , ultrasound
Background The presence of enthesitis in PsA may provide clues to disease pathogenesis, aid diagnosis and contribute to poor prognosis. Ultrasound is an invaluable tool in assessing entheseal disease, but it requires training and is time consuming. We investigated whether enthesitis may be measured by changes in serum proteins and as such allow us to better understand, diagnose and treat the condition. Objectives To use mass spectrometry (MS) based proteomics to identify protein biomarkers that may be associated with those PsA patients who suffer from enthesitis. Methods Serum was collected as part of a prospective observational study from PsA patients who fulfilled the CASPAR criteria and were ≥ 18 yrs. All patients were biologic naive and due to commence biologic treatment. We utilised the MAdrid Sonographic Enthesitis Index (MASEI) to assess US confirmed enthesitis with a score of ≥ 18 suggesting significant enthesitis and <18 determined to be non-significant. The samples were analysed using targeted MS multiple reaction monitoring (MRM) analysis with > 200 candidate proteins. The MRM data was analysed in 3 ways: 1) Raw with no normalisation 2) Normalisation to 7 stable isotopically labelled peptide spike-ins (SIL7) correcting for fluctuations in sample injections/mass spectrometry loading; and, 3) Normalisation to a set of endogenous peptides that represent total serum protein abundance (TSPA) correcting for different amounts of total serum across samples. Univariate analyses and multivariate machine learning Random Forest (RF) modelling were performed. Results 80 samples were analysed. 29 patients had a MASEI score of < 18 [36.25%] and 51 had a score > 18 [63.75%]. We identified 35 candidate proteins from all data sets that are included in Figure 1. RF multivariate analysis of all data revealed a set of peptide signatures with the ability to differentiate between MASEI scores < 18 vs ≥ 18. RF models generated from the peptide data had a testing and training AUC of 0.789 [95% CI 0.65, 0.93] 0.953 [95% CI 0.92, 0.98] (Raw), 0.83 [CI 0.74, 0.94], 0.972 [95% CI 0.96, 0.99] (TSPA7) and 0.845 [95% CI 0.72, 0.97]0.966 [95% CI 0.94, 0.99] (SIL7) respectively. Conclusion We have identified serum proteins, within this small cohort, which are associated with enthesitis in PsA. Verification of these findings in a larger, independent dataset is the next required step.Proteins related to peptide sequences for univariate + multivariate analysis.Blue (all data sets) Green (all univariate data sets and at least one multivariate) Yellow (all multivariate data sets and at least one univariate) Grey (all multivariate data sets) Red (all Univariate data sets) Pink (2 Multivariate data sets) ANT3: Adenine nucleotide translocase 3 AGT:Angiotensinogen A2HSGP: Alpha 2 HS glycoprotein ALAI: Apolipoprotein A-I ARP3: Angiopoietin related protein 3 AT3: Antithrombin III CNCC: Carboxypeptidase N catalytic chain CBG:Corticosteroid binding globulin GP3: Glutathione peroxidase 3 HSPB: Heat Shock Protein HSP 90-beta HRG: Histidine rich glycoprotein IGFBPC Insulin-like growth factor-binding protein complex acid labile subunit PEDF: Pigment epithelium derived factor SHBG: Sex hormone binding globulin PGSPD: Phosphatidylinositol-glycan-specific phospholipase D TX: Tenascin-X VDBP Vitamin D binding protein. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests None Declared.RAWTSPA7SIL7UnivariateMultivariateUnivariateMultivariateUnivariateMultivariateSHBGSHBGSHBGSHBGSHBGSHBGAGTAGTAGTAGTAT3AT3AT3AT3VDBPVDBPVDBPVDBPVDBPCBGCBGCBGCBGCalumeninCalumeninCalumeninCalumeninARP3ARP3ARP3DmX-like proteinARP3GP3GP3GP3GP3PEDFPEDFPEDFPEDFPGSPDANT3PGSPDThyroid hormone recepter betaPGSPDANT3IGFBPCHRGIGFBPCAgglutinin like proteinIGFBPCHRGA2HSGPA2HSGPPleckstrin homology like domainA2HSGPALAIALAIBeta 2 microglobulin antigenALAICNCCCNCCComplement factor BCNCCTXTXComplement component 4 binding protein alphaTXHSPBHSPBImmunoglobulin J chainHSPBProtein S100-A8Complement factor HAlpha 1-antichymotrypsinCRPImmunoglobulin heavy variable 3-7Heparin cofactor 2ProthrombinSerum amyloid P componentCadherin 13
Introduction:Enthesitis is a hallmark of psoriatic disease, but its clinical assessment is problematic in terms of diagnostic sensitivity and overlap with other comorbid conditions. Ultrasound is a useful tool that can give a more detailed assessment of enthesitis. Research demonstrates that those with persistent ultrasound entheseal disease are at risk of progressive articular damage. With limited data to guide choice between biologic therapy for psoriatic arthritis (PsA) patients, we wanted to assess the response of ultrasound-confirmed enthesitis to different forms of biologic therapies and study its utility in making more informed decisions. Methods:This was an open label observational study including patients aged ⩾18 years, who fulfil the classification criteria for PSA (CASPAR) and were due to commence on their first biologic therapy. The primary outcome was the change in MAdrid Sonographic Enthesitis Index (MASEI) score at 16 weeks of treatment. The MASEI score was also modified to assess the active elementary lesions (ActiveMASEI). Results:In all, 80 PsA patients were enrolled with 75 patients completing the study [secukinumab n = 23 and tumour necrosis factor inhibitor (TNFi) n = 52]. The mean reduction in MASEI score after 16 weeks of treatment was 3.42 with TNFi versus 1.74 with secukinumab (p = 0.097). There was a significant difference in the change in the MASEIActive score for TNFi versus secukinumab (4.37 versus 2.26; p = 0.030) and this difference was more pronounced when only power Doppler signal within 2 mm of the enthesis insertion was included (4.37 versus 2.00; p = 0.007). Clinical outcomes were similar for both classes of biologic apart from a significant reduction in regards to the Dermatology Life Quality Index and Psoriasis Area and Severity Index score with secukinumab versus TNFi. Conclusions:We have for the first time compared the effect of ultrasound-confirmed enthesitis between different forms of biologic therapies for PsA. We have seen an overall improvement in entheseal scores for both classes of medications and demonstrated a larger reduction in active entheseal disease for TNFi versus secukinumab that merits further exploration.
Rheumatoid arthritis (RA) is a chronic autoimmune condition, characterised by joint pain, damage and disability, which can be addressed in a high proportion of patients by timely use of targeted biologic treatments. However, the patients, non-responsive to the treatments often suffer from refractoriness of the disease, leading to poor quality of life. Additionally, the biologic treatments are expensive. We obtained plasma samples from N = 144 participants with RA, who were about to commence anti-tumour necrosis factor (anti-TNF) therapy. These samples were sent to Olink Proteomics, Uppsala, Sweden, where proximity extension assays of 4 panels, containing 92 proteins each, were performed. A total of n = 89 samples of patients passed the quality control of anti-TNF treatment response data. The preliminary analysis of plasma protein expression values suggested that the RA population could be divided into two distinct molecular sub-groups (endotypes). However, these broad groups did not predict response to anti-TNF treatment, but were significantly different in terms of gender and their disease activity. We then labelled these patients as responders (n = 60) and non-responders (n = 29) based on the change in disease activity score (DAS) after 6 months of anti-TNF treatment and applied machine learning (ML) with a rigorous 5-fold nested cross-validation scheme to filter 17 proteins that were significantly associated with the treatment response. We have developed a ML based classifier ATRPred (anti-TNF treatment response predictor), which can predict anti-TNF treatment response in RA patients with 81% accuracy, 75% sensitivity and 86% specificity. ATRPred may aid clinicians to direct anti-TNF therapy to patients most likely to receive benefit, thus save cost as well as prevent non-responsive patients from refractory consequences. ATRPred is implemented in R.
OBJECTIVES Predicting response to anti-tumour necrosis factor alpha (anti-TNFα) drugs at baseline remains an elusive goal in rheumatoid arthritis (RA) management. The purpose of this study was to determine if baseline genetic variants of PTPRC, AFF3, myD228, CHUK, MTHFR1, MTHFR2, CD226 and a number of KIR and HLA alleles could predict response to anti-TNF-α in rheumatoid arthritis patients. METHODS Peripheral blood samples were collected from 238 RA patients treated with anti-TNFα drugs. Genotyping was performed using biochip array technology by Randox Laboratories Ltd. and sequence specific polymerase chain reaction. Linear regression analysis was performed to investigate the role of these genotypes in predicting response to treatment, as defined by European League Against Rheumatism (EULAR) response classification and absolute change in disease activity score (DAS28). RESULTS Of 238 RA patients analysed, 50.4% received adalimumab, 29.7% received etanercept, 14.8% received infliximab, 3.4% certoluzimab and 1.7% golimumab. The MTHFR1 variant rs1801133 was significantly associated with the EULAR response, p=0.044. Patients with the HLA-DRB1*0404 allele displayed a significantly larger reduction in DAS28 compared to non-carriers (mean -2.22, -1.67 respectively, p=0.033). CD226 rs763361 was the only SNP variant significantly associated with ΔDAS28 (p=0.029). CONCLUSIONS This study has investigated individual allele associations with reductions in DAS28 across a range of anti-TNFα treatments. A combined predictive model indicates that patients with the HLA-DRB1*0404 allele and without the CD226 rs763361 polymorphism exhibit the largest reduction in DAS28 after anti-TNF-α treatment.
Abstract Objective Psoriatic nail disease is more common in PsA than in isolated skin psoriasis (PsO). The nail is closely integrated to the DIP joint entheses. US data have shown that those patients with nail disease in PsO are more likely to have systemic enthesitis. We examined whether there was a relationship between nail disease, DIP enthesitis and systemic enthesitis in established PsA. Methods Forty-six PsA participants with nail disease underwent US scanning of the nail unit and the DIP entheses along with peripheral entheseal sites according to the Madrid sonographic enthesitis index (MASEI). Results At the finger level, there was a mild to moderate correlation between nail US changes and both clinical nail disease and DIP enthesis changes (DIP US) [Spearman correlation (rS) = 0.30, P < 0.001 and rS = 0.16, P < 0.001, respectively]. At the patient level, there was a moderate correlation between the nail US score and nail psoriasis severity index score and DIP US (rS = 0.33, P = 0.024 and rS = 0.43, P = 0.003, respectively). At the patient level, there was also a positive correlation between a higher nail US score and the active peripheral enthesitis score (MASEI-active) (rS = 0.35, P = 0.018). When power Doppler was part of nail US score, similar results were demonstrated at both the finger and patient levels. Conclusion This study has demonstrated the utility of nail US imaging and the close relationship, on scanning, between the DIP entheses and the nail unit. In PsA, we have seen a correlation between active US changes at the nail and peripheral enthesitis, which requires further analysis. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov, NCT03955861.
BackgroundRadiation synovectomy with Yttrium 90Y is indicated for refractory arthritis of various aetiologies e.g. inflammatory joint diseases such as rheumatoid arthritis, seronegative arthritidies such as psoriatic arthritis and reactive arthritis, Haemophilic arthritis, Calcium pyrophosphate dihydrate (CPPD) arthritis and pigmented villonodular synovitis (PVNS)1. Treatment of inflammatory arthritis has improved due to more effective therapy and earlier treatment therefore Yttrium therapy is less commonly used.ObjectivesTo assess the response to Yttrium 90Y synovectomy in patients with Psoriatic arthritis or seronegative arthritis with synovitis affecting the knee joint in a cohort of patients who had failed conventional DMARDs, biological DMARDs or intra-articular steroid injections. To identify any possible predictors of good or poor response. To develop a standard operating procedure to improve consistency and also allow service to be potentially expanded.MethodsRetrospective chart and electronic care record review of all patients receiving Yttrium therapy in Northern Ireland from March 2016 to April 2018. Patient demographics, MRI findings, conventional and biological DMARD use, previous intra-articular steroid use were recorded. Patients were reviewed approximately six months following treatment. The medical notes were reviewed to decide whether there had been a good or poor response to treatment and data analyzed to look for factors that may predict response. The process was evaluated and we developed a standard operating procedure to improve consistency and safety going forward.Results17 patients in total received Yttrium therapy, 9 males. Age range was 18-75 with a mean 41. 10 patients were diagnosed with seronegative arthritis and 7 with psoriatic arthritis. All patients had an MRI of the affected joint(s) which confirmed synovitis in all cases. 9 MRIs showed no significant degenerative changes, 5 showed mild degenerative changes and 3 moderate/severe. All patients had previously received intra-articular steroid injection. 12 patients also were receiving or had failed treatment with a conventional or biological DMARD. Each knee received a dose of 180MBq Yttrium under direct ultrasound guidance in addition to Triamcinolone 40mg and using Lidocaine 1% local anaesthesia. 3 patients received treatment for both knees. Reviewing all patients 71% (12/17) reported good efficacy. 78% (7/9) of patients reported good efficacy in group with no osteoarthritis on MRI, 60% (3/5) in the mild osteoarthritis group and 67% (2/3) in the moderate to severe osteoarthritis group. BMI, Age, sex or underlying diagnosis did not appear to predict response in this group. There were no adverse events reportedConclusionYttrium therapy is not widely used with only one unit in Northern Ireland performing the procedure. The use of effective DMARDs and biological therapy has improved management of psoriatic and rheumatoid arthritis. In spite of this some patients still have refractory disease. We have shown in this observational study that in patients with knee synovitis despite treatment with DMARDs, biologics and intra-articular steroids, Yttrium synovectomy shows good efficacy, is a relatively low cost and generally safe treatment option for these patients. Going forward this study and our standard operating procedure will allow us to develop criteria to help select patients for Yttrium therapy and standardize our treatment.References[1] Clunie G, Fischer M (2003) EANM procedure guidelines for radiosynovectomy. Eur J Nucl Med30:BP12–BP16Disclosure of InterestsNone declared
Background Carpal tunnel syndrome (CTS) is the commonest nerve entrapment disorder of the upper limb. Diagnosis is often clinical, based on a suggestive history and physical examination. Neurophysiological studies correlate closely with clinical evaluation. The use of ultrasound has been evaluated, and a feature which consistently supports a clinical diagnosis of CTS is increased cross sectional area (CSA) of the median nerve within the carpal tunnel. Local injection with corticosteroid is generally accepted as the next step in those who remain symptomatic after conservative treatment with splinting and nonsteroidal anti-inflammatory drugs. If this is unsuccessful referral for consideration of surgery should be considered. Objectives To evaluate the utility of ultrasound in the assessment of CTS and identify predictors of response to injection. Methods Patients were recruited via primary care referrals to the rheumatology department. Inclusion criteria were age over 18 years, appropriate symptoms in the distribution of the median nerve for at least 3 months, and positive nerve conduction studies (NCS). Patients with evidence of thenar atrophy were excluded. At initial review a full symptom and medical history was taken. A Boston Carpal Tunnel Questionnaire was completed, along with visual analog scale (VAS). Ultrasound assessment was carried out by a rheumatology physician who was blinded to the above information. CSA of the median nerve was measured at the level of the proximal third of the pronator quadratus muscle and the largest CSA within the carpal tunnel. The presence or absence of tenosynovitis, Doppler signal and a bifid median nerve were noted. Steroid injection was carried out under indirect ultrasound guidance with 20mg depomedrone. Follow-up assessment was carried out 12 weeks post-injection. Repeat ultrasound scan was performed to measure the CSA of the median nerve, as before. Repeat Boston Questionnaire and VAS were recorded. After the second assessment those who had not responded adequately were referred on for consideration of surgical release. Results 52 patients attended for initial assessment, with 47 patients reattending for follow up. 53% of patients were discharged at follow up; the remainder were referred for consideration of surgery. 78.9% of patients met the criteria for defining CTS with a median nerve CSA 0.1cm2, with 77% meeting this at the entrance to the carpal tunnel, and 55.8% at the level of the pronator quadratus muscle. A bifid nerve was noted in 12 patients. There was no statistically significant relationship between the initial size of the median nerve on ultrasound and the change in Boston score. There was a statistically significant correlation between a decrease in the size of the median nerve at the entrance to the carpal tunnel and an improvement in the Boston score (r=0.42, p-value 0.003). There was no correlation between change in median nerve measurement and final outcome (discharged or referred to surgery). There was no relationship between the degree of entrapment on NCS and pre-test Boston score. There was a significant change in the Boston score of 0.944 post-injection (95% CI 0.41-1.48, p-value 0.001). There was a statistically significant change in the VAS score of 9.87 post-injection (95% CI 0.78-18.95, p-value 0.03). No patients demonstrated evidence of surrounding tenosynovitis or positive power doppler signal. Conclusion There is an overall improvement in symptoms of CTS, based on the Boston questionnaire, following corticosteroid injection. There is a clear role for the use of ultrasound to confirm diagnosis of CTS in symptomatic patients by measuring the CSA of the median nerve at the entrance to the carpal tunnel. There are no definite ultrasound or clinical prognostic indicators of response to injection. References: Disclosure of Interests: Cathy Donaghy: None declared, Ashley Elliott Speakers bureau: Novartis, Adrian Pendleton: None declared, Claire Benson: None declared, Kerry Aston: None declared, Aidan O’Neill: None declared, Roger Stewart: None declared, Mark Leith: None declared, Colette Beattie: None declared
Background:Guidelines from the Royal College of Opthalmologists in February 2018 were developed for retinal screening for patients on hydroxychloroquine, as recent evidence suggests the risk of retinal toxicity is higher than previously reported. The prevalence of retinal toxicity in long term use appears to be 7.5% and depending on dose and duration of therapy can increase to 20-50% after 20 years of therapy. Risk is increased for patients taking more than 5mg per kg per day of hydroxychloroquine, patients on Tamoxifen and those with renal impairment. The guidelines recommend the use of a standardised referral proforma to help identify patients who are high risk.Objectives:1. Audit of Hydroxychloroquine use and retinal screening in the Belfast Health and Social Care Trust (BHSCT) 2. Develop a regional referral proforma and screening service for retinal toxicityMethods:Patients who were treated with hydroxychloroquine, under the care of a consultant rheumatologist were identified on the database. A proforma was used to aid data collection and patients’ electronic records were reviewed. We audited the use of hydroxychloroquine and retinal screening against current Royal College of Ophthalmology (RCO) guidelines. We designed a standardised referral proforma and regional screening strategy in conjunction with ophthalmology colleagues.Results:There were 151 patients identified on hydroxychloroquine on the database. 40 of these patients had stopped hydroxychloroquine, 2 of which had retinal toxicity. Therefore the rate of retinal toxicity in this sample was 1.3% (2/151). There were 111 patients who remained on hydroxychloroquine treatment with a female: male ratio of 9:1. Age range was from 22 to 84, with a mean age of 55. There were 44% of patients on hydroxychloroquine for rheumatoid arthritis, 25% had systemic lupus erythematosus, 8% had Sjogrens syndrome, 6% had pallindromic rheumatoid arthritis and 13% had other connective tissue diseases. The majority (79%) of patients were on 200mg hydroxychloroquine daily and 19% were on 400mg daily. 6% of patients had an eGFR<60. No patients were on tamoxifen. 73% of patients were on hydroxychloroquine treatment for over 5 years. Retinal screening was overdue in 64% of patients.Conclusion:In this sample, only 1.3% of patients had evidence of retinal toxicity, although 64% of patients were overdue retinal screening. We developed a referral proforma and a regional screening strategy in line with RCO guidelines. In order to meet the RCO guidelines, we recognise the need for substantial investment in regional ophthalmology services.References:[1] Royal College of Ophthalmologists. (2018) Clinical Guidelines. Hydroxychloroquine and Chloroquine Retinopathy:Recommendations on Screening.Disclosure of Interests:None declared
Background: Biologic drug initiation, follow up and biosimilar switching can be complex but are protocol driven.Clinical commissioning groups (CCGs) mandate six-monthly reviews of biologic treated patients.We have 518 biologic treated patients, which equates to 1,036 clinic appointment per year.We report the successful implementation of a biologics pharmacist to aid in the assessment and follow up of biologic patients in a district general hospital with no rheumatology trainees and limited budget.The aim of the clinic was to provide a pharmacist led biologic clinic to improve patient experience and drug management.Methods: The role developed as an expansion from the holder's role as rheumatology ward pharmacist.A weekly clinic was set up and guidelines for appropriate patient referral from consultant and nurse specialist clinics were made.Eligible patients included biologic naive patients requiring assessment, education and enrolment, stable follow up patients and patients requiring biosimilar switch.The pharmacist ensures funding is approved (via blueteq) and the patient is registered with the relevant homecare company or booked in for their infusion.Training in disease activity assessment was given, and the clinic is situated near an on-going consultant led clinic, though real time support is rarely required.The post is cost neutral as it has been incorporated into an existing job plan.Results: So far 75 patients have been seen in the clinic; 44 RA, 12 AS, 18 PsA and one Behc ¸et's disease.Seeing 36 biologic initiation and 39 biologic follow up patients in total equates to saving an estimated 37.5 hours of consultant or nurse time.95% switch rate to biosimilar versions of infliximab and etanercept patients were achieved.A biologic database capturing key patient information to improve therapy management has been set up and a 30-minute weekly biologic multidisciplinary team meeting has been introduced to discuss complex patients.Capture of patient disease activity scores has been improved to monitor on-going response to therapy.Pre-biologic screening and monitoring requirements following biologic initiation are now clearly documented on clinic letters.Conclusion: Introduction of the specialist biologics clinic has enabled rapid initiation of biologic treatment in the most severely affected patients and assessment of continued response to therapy to satisfy CCG requirements.Enhanced medicines reconciliation and implementation of new audit processes and tools have rationalised the prescribing of biologics.The clinic provides the opportunity for biologic education and gives patients time to voice concerns and queries.It provides an opportunity to enhance pharmacy clinical experience and frees consultant time.Improved structure and realignment of clinical responsibilities have a significant impact on the workforce and patient management.The biologic pharmacist is now the point of contact for biologic drug queries and an essential member of the rheumatology team.
Anti-TNF response rates in radiographic and non-radiographic axial spondyloarthropathy With recent evolution of classification systems for axial spondyloarthropathy to include non-radiographic disease, there has been an increasing emphasis to treat inflammatory back pain early, potentially aiming to halt disease progression and prevent chronic damage.Current National Institute of Health and Care Excellence (NICE) criteria for commencement of anti-tumour necrosis factor (TNF) therapy in spondyloarthropathy are based on the modified New York criteria of 1984.As such, this requires radiographic changes based on plain film X-ray rather than allowing for the more sensitive modality of MRI.This criterion, therefore, excludes a group of patients that may potentially benefit from biological therapy.Published studies by Song et al (ESTHER 1 ) and Sieper et al (ABILITY-1 2 ) as well as meta-analysis by Callhoff et al 3 have shown similar response rates to anti-TNF in both radiographic and non-radiographic groups.We sought to assess whether the trial data mentioned above were similar to the clinical setting by retrospectively looking at a local biological database of patients with ankylosing spondylitis on anti-TNF therapy.Fifty-nine patients were divided into three groups: group A (N=29)-sacroiliitis on X-ray (ie, radiographic group); group B (N=23)-sacroiliitis on MRI with normal X-ray (ie, non-radiographic group) and group C (N=7)-sacroiliitis on MRI but have no record of plain film X-ray.After 3 months, the number of patients achieving an adequate response to anti-TNF, according to NICE criteria, was group A=14 (48%), group B=11 (48%) and group C=4 (57%).In those achieving adequate responses according to NICE, the percentage improvements in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), visual analogue scale (VAS) for pain and Bath Ankylosing Spondylitis Functional Index (BASFI) were similar.Average improvements in BASDAI were group A=3.96 (55%), group B=4.46 (56%) and group C=4.45 (57%).Average improvements in VAS were group A=4.47 (55%), group B=4.6 (56%) and group C=5 (57%).Average improvements in BASFI were group A=4.2 (56%), group B=2.93 (44%) and group C=2.66 (46%).In summary, this clinical review appears to show similar response rates between both radiographic and non-radiographic spondyloarthropathy groups after 3-month therapy with anti-TNF and poses the question should current guidelines for use of these medications be modified to include non-radiographic disease.
Conclusion: Annual review was appropriate as patients fulfilled NICE criteria.However, the Health, Anxiety and Depression (HADs) questionnaire was time consuming, although we didn't measure the exact time it took for each patient to complete but therefore to reduce the time it was decided to change the HADs to the PHQ9.According to NICE all patients with RA should be offered annual review and the clinic slots are 15 minutes longer to take account of the extra assessments but we are now looking at how we can implement this across all rheumatology clinics using specifically designed proformas to capture the information.