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Objectives Subjective loss of response immediately prior to routine TNFi therapy can occur in axial spondyloarthritis (axSpA). We investigated clinical outcomes in patients taking the first three licenced TNFis and correlated this with recurrence of MRI bone marrow oedema (MRI-BMO). Methods Proof-of-concept study including axSpA patients established on etanercept (ETA), adalimumab (ADA) or infliximab (IFX) reporting symptom deterioration prior to next dose. MRI/clinical data were collected prior to scheduled dose (v1), 4 days post-dose (v2) and at the time of patient-reported symptom return (v3). MRI spine/sacroiliac joints utilizing 3 T were scored using the semi-quantitative Leeds MRI scoring system. Results A total of 113 clinical assessments and MRIs were performed in 38 participants (ADA = 16, ETA = 12, IFX = 10), mean age 42.1 years ± 24.4(2SD, n = 38), 71.1% male (n = 27/38), 69.7% HLA-B27 positive (n = 23/33). At v1, all patients had high disease activity [ASDAS-CRP = 3 (2.7–3.7)] and 57.9% had MRI-BMO (number of MRI-BMO: ETA = 26, ADA = 59, IFX = 28). Improved clinical responses were seen at v2 [ASDAS-CRP −0.41(−0.81 − 0.30), P =0.018; BASDAI −0.58(−2.2 − 0.52), P =0.024]. Despite just a 4-day interval between v1 and v2, a numerical reduction in MRI-BMO lesions between v1/v2 was observed (ETA = −6, ADA = −10, IFX = −3). By v3, comparatively fewer new BMO lesions were detected in the ETA and ADA groups compared with IFX (ETA = −1, ADA = +3, IFX = +8), although the numbers were too small to enable testing for statistical significance. Conclusions Short-lived fluctuations in MRI-BMO were commoner with longer-acting agents and corresponded with subjective loss of clinical response before next scheduled TNFi dose. Larger studies are needed to confirm the possible pathogenic implications of this phenomenon.

Objective To evaluate the relationship between clinical examination/US synovitis in DMARD-naïve early PsA. Methods Eligible patients underwent matched clinical/US 44-joint assessment for tender and/or swollen joints (TJ/SJ) and US synovitis [grey scale (GS) ≥ 2 or power Doppler (PD) ≥ 1]. Statistical agreement between TJ/SJ, GS ≥ 2 and PD ≥ 1 was calculated by prevalence-adjusted and bias-adjusted κ (PABAK). To derive probabilities of GS ≥ 2/PD ≥ 1, mixed-effects logistic regression-modelled odds of US synovitis in TJ/SJ were conducted. Results In 155 patients, 5616 joints underwent clinical/US examination. Of these joints, 1039 of 5616 (18.5%) were tender, 550 of 5616 (9.8%) were swollen, 1144 of 5616 (20.4%) had GS ≥ 2, and 292 of 5616 (5.2%) had PD ≥ 1. GS ≥ 2 was most prevalent in concomitantly tender and swollen joints [205 of 462 (44%)], followed by swollen non-tender joints [32 of 88 (36.4%)], tender non-swollen joints [148 of 577 (25.7%)] and non-tender non-swollen joints (subclinical synovitis) [759 of 4489 (16.9%)]. Agreement between SJ/PD ≥ 1 was high at the individual joint level (82.6–96.3%, PABAK 0.65–0.93) and for total joints combined (89.9%, PABAK 0.80). SJ/GS ≥ 2 agreement was greater than between TJ/GS ≥ 2 [73.5–92.6% vs 51.0–87.4% (PABAK 0.47–0.85 vs PABAK 0.35–0.75), respectively]. Swelling was independently associated with higher odds of GS ≥ 2 [odds ratio (OR) (95% CI); 4.37 (2.62, 7.29); P < 0.001] but not tenderness [OR = 1.33 (0.87, 2.06); P = 0.192]. Swelling [OR = 8.78 (3.92, 19.66); P < 0.001] or tenderness [OR = 3.38 (1.53, 7.50); P = 0.003] was independently associated with higher odds of PD ≥ 1. Conclusion Synovitis (GS ≥ 2 and/or PD ≥ 1) was more likely in swollen joints than in tender joints in DMARD-naïve, early PsA. Agreement indicated that swollen joints were the better proxy for synovitis, adding to greater understanding between clinical and US assessments.

Background Up to 20% of inflammatory bowel diseases (IBD) cases may have an associated form of Spondyloarthropathy (SpA). Axial disease in SpA may vary from sporadic back pain to advanced spinal fusion, undistinguishable from Ankylosing Spondylitis (AS). Magnetic resonance imaging (MRI) is well established in the assessment of spinal disease in SpA, but axial MRI data in IBD are still sparse. In AS and axial Psoriatic Arthritis (PsA), it has previously been shown that the extent and severity of inflammatory changes of bone marrow oedema (BMO) on MRI is related to HLA-B27. Objectives The aims of this study were to describe the prevalence and extent of BMO lesions and their relationship with HLA-B27 status in IBD-related SpA with axial symptoms. Methods Consecutive MRI scans [thoracic spine (TS), lumbar spine (LS) and sacroiliac joints (SIJs)], from patients attending the Leeds Combined Rheumatology and Gastroenterology service between 2005–2015, were assessed retrospectively. Scans had been performed as part of clinical assessment for inflammatory back pain. All subjects had histological diagnosis of IBD and fulfilled ASAS classification criteria for SpA, HLA-B27 status and demographics were also collected. MRI scans were scored by consensus by two expert readers, blinded to the clinical characteristics of the patients. We used the semiquantitative (0–3) Leeds MRI Scoring System for BMO lesions representative of inflammation in the spine and SIJs, whereby a lesion graded as moderate (grade 2) is considered clinically significant. Concordant data from the two readers were used to report on definite lesions. Results MRI scans from 43 patients were available for analysis; mean age 43.4 yrs (SD 13.2, range 18.1–80.9), 25 were females (58.1%). Mean age at SpA diagnosis was 37.1 yrs (SD 11.9, range 17.1–63). HLA-B27 was positive in 15 subjects (34.9%) and was associated with younger age at SpA diagnosis (p=0.015). The median MRI score and number of BMO lesions were 2 (IQR 0–7 and 0–5, respectively), 13 patients (30.2%) scored zero, 14 subjects (32.6%) showed at least 1 clinically relevant lesion (grade ≥2). Gender, current age or age at MRI scan were not associated with HLA-B27. MRI total (whole axial skeleton) and partial (TS, LS and SIJs single analysis) score, number of BMO lesions and severe lesions (total axial skeleton and TS-LS-SIJs single analysis) were not different according to HLA B27 status. Conclusions Although the majority of IBD-related SpA do not carry HLA B27, diagnosis at a younger age was related to HLA-B27 status. Axial BMO lesions in IBD disease showed the whole spectrum of changes noted in AS. Unlike AS and axial PsA, no association was found between the extent and severity of MRI-determined axial disease and HLA-B27. Disclosure of Interest None declared

Background Tumour necrosis factor inhibitors (TNFi) are highly efficacious in axial spondyloarthritis (axSpA) with significant clinical responses mirrored in resolution of MRI determined bone marrow oedema (BMO) lesions representative of active inflammation in the sacroiliac joints (SIJ) and spine. However, symptom flare suggesting loss of response is common with many patients reporting deterioration days or weeks prior to the next dose. We hypothesised that intermittent suppression of inflammation with longer acting TNFis such as adalimumab or infliximab may be associated with a greater likelihood of recurrence of MRI determined BMO lesions than shorter acting agents such as etanercept. Objectives To explore the relationship between symptom flare immediately prior to next treatment dose and recurrence of MRI determined BMO lesions with different TNFi in axSpA. Methods Proof-of-concept, single centre study. Eligible participants were adults with axSpA established on adalimumab, etanercept or infliximab describing loss of response immediately prior to next treatment dose. Loss of response was defined as subjective “flare” or “wearing off” of drug effect before the expected duration of treatment effect. Participants attended at three points: Baseline: first day of treatment cycle (day of drug dose); Endpoint 1: 3–4 days after dose; and Endpoint 2: within 48 hours of next dose. ASDAS-CRP and whole spine and SIJ MR imaging utilising 3T MRI scanner were performed at each visit. Images were scored according to the semi-quantitative Leeds MRI scoring system by two observers blinded to participant identity and date of scan. Results 38 participants (16 adalimumab; 12 etanercept; 10 infliximab) with a total 113 MRI scans were analysed. 71% (n=27) male; 60% (n=23) HLA-B27+ with no differences between the groups; 73.7% (n=28) fulfilled mNYC for AS; the remainder were classified as nr-axSpA. 58% (n=22) had at least 1 Grade 1 BMO lesion at baseline with lesions more commonly seen with longer acting drugs (5/12 in etanercept group; 9/16 in adalimumab group; 8/10 in infliximab group) and 11 (50%) had at least 1 Grade ≥2 lesion (Table 2). There was a trend towards number and severity of BMO lesions fluctuating through the treatment cycle (Figure 1) mimicking subjective loss of response, also reflected on the ASDAS-CRP (Table 1) but this did not reach statistical significance. Conclusions This small proof-of-concept study shows subtle fluctuations on MRI changes of BMO and ASDAS-CRP corresponding to time of subjective “flare” before next scheduled TNFi dose in subjects with axSpA. Although these changes may be more common with the longer acting TNFi our data are not confirmatory. Larger studies are required to explore this concept further as these observations are potentially relevant for disease progression since cycles of inflammation and its subsequent suppression could theoretically increase the risk of new bone formation. Acknowledgements This study was sponsored by Pfizer. Disclosure of Interest R. Ansell Grant/research support from: Pfizer, H. Mathieson: None declared, M. Merashli: None declared, N. Busquets-Perez: None declared, D. McGonagle Grant/research support from: Celgene, Janssen & Pfizer, Consultant for: AbbVie, Celgene, Janssen, Novartis, UCB, Speakers bureau: Abbvie, Celgene, Janssen, UCB., H. Marzo-Ortega Grant/research support from: Janssen & Pfizer., Consultant for: AbbVie, Celgene, Janssen, Novartis, UCB. S, Speakers bureau: Abbvie, Celgene, Janssen, UCB.