Ann Rheum Dis Research Articles

PTH-074 The Presence of Total Anti-Drug Antibodies to Biologic Drugs Does not Adversely Affect Long-Term Outcomes in Crohn’s Disease Patients with Adequate Drugs Levels and Absent Free Anti-Drug Antibodies

Introduction The use of therapeutic drug monitoring (TDM) for anti-TNF drugs has become increasingly widespread over recent years. It is now used in many centres to guide clinical decisions regarding dose optimisation, the use of concomitant immunomodulators as well as switching or withdrawal of treatment. 1 TDM usually includes the measurement of serum trough levels of infliximab (IFX) or adalimumab (ADA) as well as anti-drug antibodies (ADAb). There are two different approaches to measuring ADAb; some techniques measure total ADAb (drug-ADAb complexes as well as free ADAb), whilst other measure only free ADAb. However, the clinical relevance of the differing data generated by these techniques is not yet fully understood. Methods A prospective evaluation of trough drug levels and ADAb was performed using our standard ELISA assay (LISA TRACKER, Theradiag) in 145 IBD patients on anti-TNF agents between January and May 2014. This technique measures only free ADAb. The samples were also anaylsed using an ELISA assay that measures total ADAb (IDKmonitor, Immundiagnostik). Long term outcomes were evaluated for 21 (17 IFX, 4 ADA) patients with Crohn’s disease (CD) who were found to have negative free ADAb but positive total ADAb. Outcome assessments were made by review of a prospectively maintained database, with a mean follow-up period of 22 months. Clinical outcome measures included; the need to escalate/switch/withdraw biologic treatment, infusion/injection-site reactions, documented clinical flare (HBI > 5) and need for steroid treatment. Biochemical outcome measures included; CRP > 5 mg/L and faecal calprotectin >150 ug/g. The subsequent development of positive free ADAb and subtherapeutic/undetectable drug levels were also collected as outcome measures. Results Anti-drug antibody (ADAb) detection: Of the 21 CD patients with positive total ADAb and negative free ADAb at the time of initial sampling, 3 (14%) went on to subsequently develop positive free ADAb during the follow-up period. Sixteen patients (75%) were taking concomitant immunomodulators, including all 3 patients who subsequently developed free ADAb. The mean IFX trough level in patients who went on to develop free ADAb was 1.05 ug/ml, compared to 4.04 ug/ml in those who did not. Outcomes: All 3 (100%) of the patients who developed positive free ADAb subsequently went on to have subtherapeutic or undetectable drug levels and required a switch in anti-TNF therapy. Two of the 3 (67%) had a flare in disease activity with an elevated faecal calprotectin. Two (67%) also developed significant infusion reactions. Of the remaining 18 patients who did not subsequently developed free ADAb, only one patient (6%) required a switch in anti-TNF, 4 (22%) developed clinical flares and 3 (17%) required steroid treatment. None of the 18 patients who remained free ADAb negative had undetectable drug levels during the follow-up period. Conclusion Long-term outcomes were not shown to be adversely affected by the presence of total ADAb, in the absence of free ADAb and adequate drug levels. However, patients who subsequently developed free ADAb and subtherapeutic or undetectable drug levels had unfavourable long-term outcomes. The presence of total ADAb does not appear to accurately predict the development of free ADAb. This data supports the use of ELISA techniques which measure free ADAb as well as drug levels. Our study and other similar work, 2 suggests that quantification of drug-ADAb complexes (total ADAb) appears to be less relevant to long-term clinical outcomes and therefore, less informative to clinical decision making. References 1 Ben-Horin S, Chowers Y. Tailoring anti-TNF therapy in IBD: drug levels and disease activity. Nature Reviews Gastroenterology & Hepatology 2014; 11 :243–255. 2 van schouwenburg, et al. Long-term measurement of anti-adalimumab using pH-shift-anti-idiotype antigen binding tests shows predictive value and transient antibody formation. Ann Rheum Dis . 2013; 72 :1680–6. Disclosure of Interest None Declared

Tocilizumab for systemic sclerosis: implications for future trials

Systemic sclerosis is a chronic autoimmune disease that causes high morbidity and increases mortality. Although treatments have become available for some manifestations such as pulmonary arterial hypertension, there is still no approved therapy for fibrotic manifestations and the overall course of disease. 1 Kowal-Bielecka O Landewe R Avouac J et al. EULAR recommendations for the treatment of systemic sclerosis: a report from the EULAR Scleroderma Trials and Research group (EUSTAR). Ann Rheum Dis. 2009; 68: 620-628 Crossref PubMed Scopus (500) Google Scholar However, following findings about the pathogenesis of fibrotic diseases, several new targeted therapies are being tested in clinical studies. 2 Distler O Cozzio A Systemic sclerosis and localized scleroderma-current concepts and novel targets for therapy. Semin Immunopathol. 2016; 38: 87-95 Crossref PubMed Scopus (72) Google Scholar , 3 Ramming A Dees C Distler JH From pathogenesis to therapy—perspective on treatment strategies in fibrotic diseases. Pharmacol Res. 2015; 100: 93-100 Crossref PubMed Scopus (15) Google Scholar Safety and efficacy of subcutaneous tocilizumab in adults with systemic sclerosis (faSScinate): a phase 2, randomised, controlled trialTocilizumab was not associated with a significant reduction in skin thickening. However, the difference was greater in the tocilizumab group than in the placebo group and we found some evidence of less decline in forced vital capacity. The efficacy and safety of tocilizumab should be investigated in a phase 3 trial before definitive conclusions can be made about its risks and benefits. Full-Text PDF

Loss of Peristaltic Reserve, Determined by Multiple Rapid Swallows, Is the Most Frequent Esophageal Motility Abnormality in Patients With Systemic Sclerosis.

We assessed peristaltic reserve using multiple rapid swallows (MRS) during esophageal high-resolution manometry (HRM) of 111 patients with systemic sclerosis (89 women; ages, 42-64 y). We performed a retrospective analysis of HRM studies that included MRS in patients with systemic sclerosis, performed at 2 tertiary referral centers, and compared data with those from 18 healthy volunteers (controls). HRM findings were analyzed according to the Chicago Classification to provide an esophageal motility diagnosis. Response to MRS was evaluated for the presence of contraction and for augmentation, defined as the distal contractile integral after MRS greater than the median distal contractile integral of 10 supine swallows. Esophageal motility diagnoses included 41% with absent contractility, 31% with normal motility, 23% with ineffective esophageal motility, and 5% that met the criteria for other esophageal motility disorders. Contraction (37%) and peristaltic augmentation (18%) after MRS were observed less frequently in patients with systemic sclerosis than in controls (83% and 100%, respectively). Impaired peristaltic reserve, as assessed with MRS during HRM, is therefore the most common esophageal motility finding among patients with systemic sclerosis.

Coexistence of Sarcoidosis and Sjögren's Syndrome: A Case-Report

SESSION TITLE: Diffuse Lung Disease Global Case Reports SESSION TYPE: Global Case Report Poster PRESENTED ON: Tuesday, October 27, 2015 at 01:30 PM - 02:30 PM INTRODUCTION: Sarcoidosis and Sjögren's syndrome (SS) are both multisystemic diseases of unknown etiology. Sarcoidosis is a multisystemic granulomatous disease of unknown etiology. Although, lungs and the tracheobronchial tree are the most common involvement sites in sarcoidosis it can rarely effect the salivary and lacrimal glands. On the other hand, SS mainly affects the exocrine glands, but it may also have systemic manifestations. Occasionally some features of sarcoidosis may mimic SS when parotid and/or lacrimal gland involvement is present. Although they are different clinical entities there are several reports suggestive of sarcoidosis and coexisting Sjögren's syndrome in the literature (1, 2). CASE PRESENTATION: A 58 years-old Caucasian female presented with dry cough, exertional dyspnea, progressive dry mouth and dry eyes. Physical examination was unremarkable except dryness of oral mucosa and bilateral basal crackles. Laboratory examinations revealed an increased erythrocyte sedimentation rate, C-reactive protein. Routine hematological laboratory and blood chemistry values were normal. Chest radiograph showed bilateral hilar lymphadenopathy and lower zone reticular infiltrates. Chest computed tomography revealed multiple mediastinal and bilateral hilar lymphadenopathies in addition to bilateral pulmonary nodules with peribronchovascular involvement. A mild restrictive ventilatoty defect and mild reduction in carbon monoxide diffusion capacity was observed on pulmonary function tests. She underwent bronchoscopy. A transbronchial fine needle aspiration biopsy from the right lower paratracheal station revealed non-caseating granulomatous inflammation. Serum angiotensin converting enzyme level was elevated. Antinuclear antibody and antibodies against SS-A / Ro were positive. Bilateral Shirmer's tear test yielded positive. Histopathological examination of minor salivary glands showed periductal lymphocytic infiltration. The patient was diagnosed with coexisting SS and sarcoidosis. Treatment with prednisolon and hidroxychloroquine were started. During a 2 year follow-up clinical symptoms and laboratory findings normalized. Radiographic findings regressed. Corticosteroids were tapered and stopped. Until now, the patient has been treated with hidroxychloroquine with no major symptoms and findings. DISCUSSION: Our patient was considered as sarcoidosis on the basis of compatible clinical, radiological findings and histopathological verification of noncaseating granulomas in mediastinal lymph node biopsy. Elevated serum angiotensin converting enzyme also supported sarcoidosis diagnosis. On the other hand, diagnosis of SS was based on dry eye and dry mouth sympthoms, positive bilateral Schirmer's test, the presence of characteristic autoantibody (anti-Ro/SS-A) in addition to evident lymphocytic sialoadenitis in salivary gland biopsy (3). Sarcoidosis and SS share similar immunologic and histopathological features. Making a differential diagnosis between these two diseases may be difficult in cases that present with common clinical features. On the other hand, it was shown that the frequency of sarcoidosis is higher in patients with SS than in the general population (2). Immunologic profile with a high ANA, RF and anti-Ro/SS-A was shown to have an important role in differentiating between sarcoidosis mimicry or coexistence with SS in addition to biopsy. CONCLUSIONS: We emphasize that both sarcoidosis and SS may coexist as illustrated in our case. Analysis of autoantibodies may be very helpful in making differential diagnosis or deciding their coexistence. Currently, the acceptance of sarcoidosis as an exclusion criteria for SS diagnosis may lead to under-diagnosis of SS in these cases. A revision for exclusion criteria of SS diagnosis might be necessary with this respect. Reference #1: Mansour MJ, et. al. Coexistence of Sjogren's syndrome and sarcoidosis: a report of five cases. J Oral Pathol Med 2007:36:337-341. Reference #2: Ramos-Casals M, et. al. Sarcoidosis or Sjogren Syndrome? Clues to defining mimicry or coexistence in 59 cases. Medicine 2004: 83: 85-95. Reference #3: Vitali C, et. al. Classification criteria for Sjogren's syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis 2002;61:554-558. DISCLOSURE: The following authors have nothing to disclose: Asli Gorek Dilektasli, Ezgi Demirdogen Cetinoglu, Eda Durmus, Esra Uzaslan, Ercument Ege, Mehmet Karadag No Product/Research Disclosure Information

The efficacy of a Mediterranean type diet on symptoms of osteoarthritis – a pilot study

Osteoarthritis (OA) is a group of chronic, painful, disabling conditions affecting synovial joints where the pathology includes damage and loss of articular cartilage, irregular remodelling and erosion of sub-articular bone, synovial distension and inflammation(1). Whilst current management strategies include exercise, weight loss and pharmacological therapies, there is evidence to suggest that particular food sources consistent with a Mediterranean type diet (e.g. rich in omega-3 fatty acid) may slow the pathogenesis of degenerative joint diseases(2) and moderate markers of inflammation(3). Consequently, following a diet which is plant based, favours olive oil over animal fats, and is high in fibre, vegetables, and fruits, combined with a low intake of foods which are associated with increased inflammation (e.g. meat, dairy, fat and sugar) may reduce joint degradation and inflammation associated with OA. The primary aim of the present pilot study was to assess whether following a Mediterranean type diet would moderate the physiological and perceptual symptoms of participants diagnosed with OA. Following full institutional ethical approval according to the guidelines laid down in the Declaration of Helsinki, 45 participants diagnosed with OA were randomly allocated to an experimental or control group to participate in either Part A or Part B of this 4 month study. In Part A (EXP = 19; CON = 6), participants completed the previously validated Arthritis Impact Measurement Scales Health Status Questionnaire (AIMS2) and a 1 week food frequency questionnaire on enrolment, halfway through the study (month 2) and at the end of the study (month 4). In Part B (EXP = 13; CON = 7), participants provided the same data but gave a venous blood sample on enrolment and at month 4 for analysis of serum cartilage oligomeric matrix protein (sCOMP) (a marker of cartilage degradation) instead of the AIMS2 questionnaires. The CON groups were asked to maintain their usual activities and dietary practices, whereas the EXP groups were asked to follow a dietary practice which was consistent with a Mediterranean type diet. Participants in the EXP group demonstrated lower levels of sCOMP from pre- to post-intervention (pre- = 14.1 ± 4.9 U/L; post- = 13.1 ± 5.2 U/L, Cohen's d = 0.413), although this was not significant (p > 0.05). Participants in the CON group experienced no change in sCOMP from pre- to post-intervention (pre- = 9.6 ± 1.4 U/L post- = 10.0 ± 2.4 U/L, Cohen's d = -0.154). None of the components of the AIMS2 questionnaire were changed over the 4-month study in the CON group, but the Affect component significantly decreased by 19% from pre- to post dietary intervention (p = 0.02) in the EXP group. The results of this pilot study indicate that a 4-month dietary intervention which prescribes a Mediterranean type diet for patients diagnosed with OA results in a significant improvement in the perceptual markers of OA and a moderate reduction in sCOMP – a marker of cartilage degradation. These findings suggest that simple modifications to diet may help patients with OA manage the progression of their disease and improve their quality of life. The findings of this study should be supported with an increased sample size to statistically confirm the observed meaningful effect sizes, and a greater range of biomarker analysis (both inflammatory and degradation markers) to assess the impact on the physiological progression of OA. 1. Hutton CW (1989) Ann Rheum Dis 48, 958–961 2. Knott, Avery NC, Hollander AP, et al. (2011) Osteoarthritis Cartilage 19, 1150-1157. 3. Dean E & Hansen RG (2012) Arthritis 2012, 1-28.

Maternal Genetics Variants in PTPN22, TNF and VDR Genes Increase the Risk of Pediatric Lupus Nephritis. A Pilot Study.

Maternal Genetics Variants in PTPN22, TNF and VDR Genes Increase the Risk of Pediatric Lupus Nephritis. A Pilot Study.

How Do We Classify Rheumatoid Arthritis in Established Disease — Can We Apply the 2010 American College of Rheumatology/European League Against Rheumatism Classification Criteria?

The creation of the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for rheumatoid arthritis (RA; Figure 1)1 sought to address some of the criticisms of the previous ACR criteria set published in 1987 (Figure 2)2 — namely that they were insensitive, particularly early in the disease course, and that this led to the exclusion of many patients with early disease from clinical trials and research studies3. As a result, there was an absence of evidence regarding the efficacy of new treatments in this group of patients, who may have had the potential to benefit the most4,5. Thus, 1 aim of the 2010 criteria was to identify those patients with early RA with the key purpose of rapid disease-modifying antirheumatic drug (DMARD) initiation. However, the ability to classify patients as having RA is important at all phases of the disease, early and late. A case definition is required as an entry criterion not only to clinical trials, but also a consensus for inclusion in longterm observational studies and the whole spectrum of research in RA. Numerous studies have tested the validity of the new criteria since their publication against various standards6, but they have generally been applied in patients with relatively short duration of symptoms, ranging from < 3 months to < 2 years. Thus, the question remains, can we extend these classification criteria to patients with established disease? Figure 1. 2010 ACR/EULAR Classification criteria for RA1. ACR: American College of Rheumatology; EULAR: European League Against Rheumatism; RF: rheumatoid factor; ACPA: anticitrullinated protein antibodies; CRP: C-reactive protein; ESR: erythrocyte sedimentation rate; RA: rheumatoid arthritis. From Aletaha, et al. Ann Rheum Dis 2010;69:1580–8; with permission. Figure 2. 1987 ACR Classification criteria for RA2. ACR: American … Address correspondence to Professor D.P.M. Symmons, Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, The University of Manchester, Manchester Academic Health Science Centre, UK. E-mail: deborah.symmons{at}manchester.ac.uk

SP0209 Technical Validity of MRI for Evaluating Joint Damage and Inflammation in Rheumatoid Arthritis

Magnetic resonance imaging (MRI) allows quantitative (volume or, for synovitis, early contrast enhancement after intravenous contrast injection) as well as less detailed (qualitative: presence/absence; semiquantitative: scoring) evaluation of synovitis, bone...

SP0063 Imaging Biomarkers in Undifferentiated Arthritis. Are Mri/Us Useful Tools?

Ultrasonography (US)In a systematic literature search up to 2009 [1], no US publications on pure undifferentiated populations and only 2 publications in mixed populations (not optimal) [2,3] were available. In...

SP0002 Pathogenic Mechanisms in Giant-Cell Arteritis

Giant-cell arteritis (GCA) is a chronic inflammatory disease of large vessels. The epidemiology of GCA suggests that genetic background play a role in pathogenesis. Several polymorphisms have been associated with...

SAT0078 The Need to Perform an Impact Study before Using Referral Models for Axial Spondyloarthritis in Daily Practice

BackgroundUnfortunately, only a small part of all published prediction models is used in daily practice, an explanation can be a lack of efficacy or practical feasibility. Therefore prediction modeling research...

AB1060 Are There Gender-Specific Differences in Patient Characteristics at Initiation of Biologic Treatment in Ankylosing Spondylitis and Psoriatic Arthritis?

BackgroundThe prevalence of ankylosing spondylitis (AS) is 2-3 times higher in men compared to women whereas psoriatic arthritis (PsA) is generally considered a disease affecting both genders equally. Recent studies...

THU0111 Ra Patients with Inadequate Response to Oral MTX Maintain Satisfactory Disease Control and Durable Long-Term Response When Switched to SC MTX Monotherapy

BackgroundMethotrexate (MTX) is the cornerstone of rheumatoid arthritis (RA) therapy, but many patients do not achieve adequate response to oral therapy for reasons of tolerability or efficacy.1,2 Subcutaneous (SC) MTX...

OP0274 Subclinical Diffuse Dermal Involvement is Detectable by High Frequency Ultrasound in Patients with Limited Cutaneous Systemic Sclerosis

BackgroundSkin manifestations are critical in the initial diagnosis of systemic sclerosis (SSc) and in the subsequent sub-classification into the different subsets of the disease (1). The modified Rodnan skin score...

AB0666 The Survival of the anti Tumor Necrosis Factor Alpha in Patients with Ankylosing Spondylitis as First Line Treatment in Slovenian Nationwide Registry

BackgroundAnkylosing spondylitis is potentially debilitating rheumatic disease. The introduction of biologics in treatment armamentarium made a radical change in prognosis. Anti tumor necrosis factor alpha (TNF-a) are the only biologics...

FRI0227 Analysis of Periarticular Bone Changes in Patients with Cutaneous Psoriasis without Associated Psoriatic Arthritis

BackgroundSkin disease predates the onset of psoriatic arthritis (PsA) in about 60% of cases [1]. The transition from skin disease to joint involvement is only partially characterized. Erosive changes and...

SAT0304 Correlation between Three Different Methods to Evaluate Dermal Thickness in Different Skin Areas of Systemic Sclerosis Patients

BackgroundSystemic sclerosis (SSc) is characterized by increased dermal thickness (DT) (1,2). The modified Rodnan skin score (mRSS) is a standard outcome measure used to evaluate the severity and extent of...

FRI0133 Loss of Anterior Concavity of 1St Sacrum in Assessment of the Modified Stoke Ankylosing Spondylitis Spinal Score: MR Correlation

BackgroundIn assessment of the modified Stokes Anklyosing Spondylitis Spinal Score (mSASSS), squaring is an important factor of scoring. However, the 1st sacrum (S1) is often underestimated in the assessment of...

AB0942 Comparison between Enthesopathy in Psoriasis and Psoriatic Arthritis. (Clinical and Ultrasonographic Study)

BackgroundMany studies revealed subclinical enthesitis in psoriasis patients without any rheumatic complain. Most of these studies utilize diagnostic high frequency ultrasound (US) in detection of abnormal changes at the enthesis1,2....

OP0217 Defining Disease Activity Sates and Minimal Clinically Important Improvement (MCII) with the EULAR Primary SjÖGren's Syndrome Disease Activity Index (ESSDAI)

ObjectivesTo determine disease activity levels and clinically important changes with the recently developed and validated [1] EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI), and to assess their relevance for conducting...