Introduction Research into novel therapies for rare, immune-mediated inflammatory diseases (IMIDs) faces significant challenges, including small patient populations, complex clinical trial design and difficulties in patient recruitment. Patients with Behçet’s disease (BD), idiopathic inflammatory myopathies (IIM) and IgG4-related disease (IgG4-RD) typically undergo treatment involving prolonged administration of high-dose glucocorticoids and immunosuppressants. Both are associated with an increased risk of infection. Additionally, glucocorticoids carry long-term toxicity risks. Thus, there is an urgent need to develop more targeted and effective anti-inflammatory treatments. Given the activation of the type 1 interferon pathway in BD, IIM and IgG4-RD, inhibition of the Janus kinase (JAK) STAT pathway emerges as a promising therapeutic strategy. The Drug Rediscovery in IMIDs (DRIMID) consortium aims to conduct a prospective pilot basket trial to investigate the effects of filgotinib, a JAK1 preferential inhibitor approved for ulcerative colitis and rheumatoid arthritis, on disease activity, quality of life and safety in patients with refractory BD, IIM and IgG4-RD.Methods and analysis In this investigator-initiated, multicentre, open-label phase 2 study, up to 60 patients with rare IMIDs will be enrolled for a 26-week treatment period with filgotinib 200 mg once daily. The trial consists of two stages, each involving a consecutively treated cohort of up to 20 patients per disease. An interim analysis is conducted between these stages, where the trial will proceed only in diseases showing potential effectiveness. Baseline, 3-month and 6-month assessments will include data on quality of life, disease activity, corticosteroid toxicity and biomarkers. The coprimary endpoints are disease activity and quality of life across and within each disease.Ethics and dissemination The study received approval from the Medical Research Ethics Committee in Utrecht, Netherlands. A Data Safety Monitoring Board has been established to monitor the trial’s safety and progress.Trial registration number NCT06285539.

Objective Combination therapy with rituximab and belimumab is a novel treatment strategy for severe SLE and lupus nephritis. Phase II studies have shown promising results, although long-term data are currently lacking. To address this, we analysed outcomes of patients with severe treatment-refractory SLE who previously participated in the phase II Synbiose Study, with a particular focus on immunological parameters.Methods Eight patients continued belimumab treatment beyond the 2-year duration of the original trial. We conducted a descriptive study to evaluate the course of treatment and immunological parameters over an extended follow-up. Our analyses include blood cell counts, immunoglobulins, autoantibodies, complement markers and clinical disease activity parameters. Additionally, we examined long-term effects on the B cell compartment employing high-sensitivity flow cytometry.Results Over a median follow-up period of 6.8 years, six out of eight previously treatment-refractory patients maintained long-term clinical remission, while two experienced a major flare. Among those in remission, two patients achieved immunosuppression-free remission, and four continued belimumab. Long-term effects on humoral (auto-)immunity were a persistent decrease in IgM levels, while IgG normalised. Most patients maintained low autoantibody titres, and complement markers remained normal. On the cellular level, belimumab treatment after rituximab prevented B cell repopulation. Notably, patients exhibited a stable reduction of double-negative (DN) B cells, irrespective of continuing or stopping belimumab.Conclusions Long-lasting remission was observed in patients with SLE following combination treatment with rituximab and belimumab. We observed no significant hypogammaglobulinaemia and, notably, persistent reduction of DN B cells.

BackgroundRecurrence risk of systemic lupus erythematosus (SLE)-associated venous thromboembolism (VTE) is unclear. AimTo determine the recurrence risk of SLE-associated VTE overall and by presence of provoking factors and SLE flares. MethodsA multicenter, retrospective cohort study was conducted among patients with first SLE-associated VTE who discontinued anticoagulation. SLE flares were defined as Systemic Lupus Erythematosus Disease Activity Index 2000 greater than 4. The primary outcome was recurrent VTE. Incidence rates and cumulative incidences were calculated by presence of provoking factors and antiphospholipid syndrome (APS) at index VTE. The hazard ratio (HR) for recurrence after SLE flare-associated index VTE was estimated with Cox regression, adjusted for provoking factor presence and APS. ResultsEighty patients were included with 21 recurrent VTEs in median 8 years. For provoked index VTE, the recurrence rate in patients without APS was 1.1 per 100 person-years (PY; 95% confidence interval [CI], 0.1-3.1) and in the presence of APS 3.5 per 100 PY (95% CI, 0.9-8.9), yielding cumulative incidences of 7.5% (95% CI, 1.2%-21.7%) and 31.4% (95% CI, 6.3%-61.6%) respectively. For unprovoked index VTE, these analogous rates were 3.8 per 100 PY (95% CI, 1.2-9.0) and 16.7 per 100 PY (95% CI, 4.5-42.7), with cumulative incidences of 33.7% (95% CI, 10.7%-58.9%) and 54.2% (95% CI, 10.7%-84.5%), respectively. Forty-six index VTEs were flare associated, and the adjusted HR for recurrence was 0.4 (95% CI, 0.1-1.8) compared to those without flares at their index VTE. ConclusionAntiphospholipid syndrome is the main determinant for recurrence risk of SLE-associated VTE irrespective of presence of a provoking factor. Future research should attempt to confirm that flare-associated VTE has a lower recurrence risk.

OBJECTIVES:To evaluate the success rate of glucocorticoid discontinuation and to study which factors are associated with successful discontinuation. METHODS:Data from two treat-to-target studies, BeSt (target Disease Activity Score (DAS) ≤2.4) and IMPROVED (target DAS <1.6), were evaluated for all patients initially treated with a tapered high dose of prednisone with conventional synthetic disease-modifying antirheumatic drugs. Prednisone was discontinued when DAS ≤2.4 was maintained for 28 weeks in BeSt and as soon as DAS was <1.6 in IMPROVED. Discontinuation was considered successful if the target was maintained at the next visit. Logistic regression analyses were performed to identify predictors of successful discontinuation. A mixed effects logistic regression model was used to assess whether primary versus secondary discontinuation was as successful. RESULTS:In the BeSt study, 40% (47 of 93) of patients flared after primary prednisone discontinuation, and of the other 60% (56 of 93), 38% had to restart later. Of those who restarted (secondary discontinuation), 47% (17 of 35) again flared. In IMPROVED, after primary discontinuation 39% (158 of 400) flared, and of the other 61% (242 of 400), 40% had to restart later. After secondary discontinuation 49% (68 of 139) flared. Only in IMPROVED a secondary attempt was less successful (BeSt OR 0.71, p=0.45; IMPROVED OR 0.60, p=0.01). A lower DAS both at baseline and stop visit and male gender (in IMPROVED) were associated with successful primary discontinuation. CONCLUSION:Primary glucocorticoid discontinuation resulted in direct loss of disease control in approximately 40% and secondary in 50% of patients. 'Standard' baseline characteristics seem insufficient to personalise the duration of temporary glucocorticoid bridging, but the DAS at the time of discontinuation might provide guidance.

Background Since the start of the COVID-19 pandemic, a hyperinflammatory syndrome has appeared which develops weeks after a SARS-CoV-2 infection. This multisystem inflammatory syndrome has been described mainly in children (MIS-C), but lately has also been found in adults (MIS-A). Case description We present a case of a woman with MIS-A. She had fever, diarrhoea, hypotension, laboratory abnormalities with high inflammatory markers, coagulation parameters, troponin-T, N-terminal pro-brain natriuretic peptide (NT-proBNP). Her electrocardiogram had marked diffuse ST-depressions. She was diagnosed in an early stage of MIS-A and treated successfully with immune suppression, antiaggregants and anticoagulants. Conclusion MIS-A and MIS-C are similar, potentially life-threatening inflammatory syndromes which can lead to severe cardiac dysfunction and cardiovascular failure. For effective treatment and prevention of complications, timely recognition is essential. Clinicians should therefore be mindful of this multisystem inflammatory syndrome, not just in children but also in adults.

Background: The effect of inflammatory arthritis (IA) on fertility has been mainly studied in women. Multiple factors associated with lower fertility rate in women can also be present in male patients with IA (1). The fertility rate in men with IA, however, has never been studied. Objectives: To describe the fertility rate (number of biological children per individual) of men with IA. Methods: We performed a multicenter cross-sectional retrospective study conducted in eight Dutch hospitals. Men with IA (Rheumatoid Arthritis (RA), Juvenile Idiopathic Arthritis (JIA) and Spondyloarthritis (SpA)) who were over 40 years old and indicated that their family size was complete were invited to participate. Men who were still planning on having biological children were excluded. Participants completed a digital questionnaire that included fertility-related questions and questions regarding their demographic and clinical information. To analyze the impact of IA on male fertility rate, patients were divided into groups according to the age at the time of their diagnosis: age<30 years, age 31-40 years and age>41 years. Results: In total 628 participants diagnosed with IA were included. The response rate 34.87%. Information regarding their age, age at diagnosis, clinical diagnosis and number of children is presented per group in Table 1. Regarding the total number of children per man, there was a statistically significant difference between the three groups (p=<0.005). The mean total number of children was significantly lower in men diagnosed at age<30 years (1.39 {SD 1.41}) and at age 31-40 years (1.60 {SD 1.35}) compared to those diagnosed after at age>41 years (1.88 {SD 1.14}). Compared to men from the general population of the Netherlands, the total number of children of men diagnosed at age>41 years was not statistically different (1.88 vs 1.80, respectively). Table 1. Participants’ basic demographic and clinical characteristics, including the number of biological children per men. All patients IA diagnosed at age <30 years IA diagnosed at age 31-40 years IA diagnosed at age >41 years Total, n (%) 628 137 (21.82) 149 (23.73) 342 (54.46) Age, mean (SD) 57.17 (9.98) 53.01 (9.96) 52.76 (7.35) 61.06 (9.47) Diagnosis, n (%) •iRA 297 (47.29) 42 (30.66) 67 (44.97) 188 (55.32) •AJIA 10 (1.59) 10 (6.25) 0 (0) 0 (0) •ISpA (incl. PsA) 320 (50.96) 90 (65.69) 83 (55.70) 147 (42.98) Age at diagnosis, mean (SD) 41.29 (13.08) 26.27 (9.15) 36.99 (5.66) 49.98 (9.70) Disease duration, mean (SD) 15.89 (11.88) 26.48 (12.57) 15.70 (8.52) 11.30 (9.87) Number of biological children, mean (95% CI) 1.71 (1.60-1.81) 1.39 (1.15-1.63 ) a,b 1.60 (1.38-1.82 ) a 1.88 (1.75 -2.01) a p< 0.05 compared to those diagnosed age >41 years b p< 0.05 compared to those diagnosed age >31-40 years Conclusion: This is the largest study ever conducted to evaluate the impact of IA on male fertility. We demonstrated that men diagnosed with IA before and during their reproductive years have a lower fertility rate than those men diagnosed with IA after their reproductive years. Multiple mechanisms (biological and non-biological) can be responsible for this association. More research is needed to identify the causes of these lower fertility rates in men with IA. References: [1]Perez-Garcia LF, Te Winkel B, Carrizales JP, Bramer W, Vorstenbosch S, van Puijenbroek E, et al. Sexual function and reproduction can be impaired in men with rheumatic diseases: A systematic review. Semin Arthritis Rheum. 2020;50(3):557-73. Figure 1. Total number of biological children (mean and SD) per group. Acknowledgements: The authors would like to acknowledge Ron Buijs, data manager of the Department of Rheumatology of the Erasmus MC, for his technical support with regards to data collection. Disclosure of Interests: Luis Fernando Perez-Garcia Consultant of: Galapagos, Esther Röder: None declared, Robbert Goekoop: None declared, Johanna Hazes: None declared, Marc R Kok Consultant of: Novartis, Grant/research support from: Novartis, Petra Kok: None declared, Hieronymus TW Smeele: None declared, Ilja Tchetverikov: None declared, J.H. van der Kaap: None declared, Annette van der Helm - van Mil: None declared, Bouwe Krijthe: None declared, Radboud Dolhain Speakers bureau: UCB, Roche, Abbvie, Genzyme, Novartis, Consultant of: Galapagos, Grant/research support from: UCB

Objectives The impact of inflammatory arthritis (IA) on male fertility remains unexplored. Our objective was to evaluate the impact of IA on several male fertility outcomes; fertility rate (number of biological children per man), family planning, childlessness and fertility problems. Methods We performed a multicentre cross-sectional study (iFAME-Fertility). Men with IA 40 years or older who indicated that their family size was complete were invited to participate. Participants completed a questionnaire that included demographic, medical and fertility-related questions. To analyse the impact of IA on fertility rate, patients were divided into groups according to the age at the time of their diagnosis: ≤30 years (before the peak of reproductive age), between 31 and 40 years (during the peak) and ≥41 years (after the peak). Results In total 628 participants diagnosed with IA were included. Men diagnosed ≤30 years had a lower mean number of children (1.32 (SD 1.14)) than men diagnosed between 31 and 40 years (1.60 (SD 1.35)) and men diagnosed ≥41 years (1.88 (SD 1.14)).This was statistically significant (p=0.0004).The percentages of men diagnosed ≤30 and 31–40 years who were involuntary childless (12.03% vs 10.34% vs 3.98%, p=0.001) and who reported having received medical evaluations for fertility problems (20.61%, 20.69% and 11.36%, p=0.027) were statistically significant higher than men diagnosed ≥41 years. Conclusions This is the first study that shows that IA can impair male fertility. Men diagnosed with IA before and during the peak of reproductive age had a lower fertility rate, higher childlessness rate and more fertility problems. Increased awareness and more research into the causes behind this association are urgently needed.

Objectives To develop a prediction model to guide annual assessment of systemic sclerosis (SSc) patients tailored in accordance to disease activity.Methods A machine learning approach was used to develop a model that can identify patients without disease progression. SSc patients included in the prospective Leiden SSc cohort and fulfilling the ACR/EULAR 2013 criteria were included. Disease progression was defined as progression in ≥1 organ system, and/or start of immunosuppression or death. Using elastic-net-regularisation, and including 90 independent clinical variables (100% complete), we trained the model on 75% and validated it on 25% of the patients, optimising on negative predictive value (NPV) to minimise the likelihood of missing progression. Probability cutoffs were identified for low and high risk for disease progression by expert assessment.Results Of the 492 SSc patients (follow-up range: 2–10 years), disease progression during follow-up was observed in 52% (median time 4.9 years). Performance of the model in the test set showed an AUC-ROC of 0.66. Probability score cutoffs were defined: low risk for disease progression (<0.197, NPV:1.0; 29% of patients), intermediate risk (0.197–0.223, NPV:0.82; 27%) and high risk (>0.223, NPV:0.78; 44%). The relevant variables for the model were: previous use of cyclophosphamide or corticosteroids, start with immunosuppressive drugs, previous gastrointestinal progression, previous cardiovascular event, pulmonary arterial hypertension, modified Rodnan Skin Score, creatine kinase and diffusing capacity for carbon monoxide.Conclusion Our machine-learning-assisted model for progression enabled us to classify 29% of SSc patients as ‘low risk’. In this group, annual assessment programmes could be less extensive than indicated by international guidelines.

Background: Disease course in Systemic Sclerosis (SSc) ranges from mild, to severe with progressive organ involvement within months. Guidelines for follow-up are mainly based on expert consensus, and advocate annual assessment. So far, no data driven guidelines exist that describe tailormade systematic assessments for individual patients in line with individual disease course. Objectives: To develop a prediction model to guide annual assessment of SSc patients tailored in accordance to disease activity. Methods: A machine learning approach was used to develop a model that can identify patients without disease progression. SSc patients included in the prospective Leiden SSc cohort and fulfilling the ACR/EULAR 2013 criteria were included. The primary endpoint in the prediction model was disease progression which was defined as progression in ≥1 organ system, and/or start of immunosuppression or death between the two most recent visits. Using elastic-net-regularization, and including 90 independent clinical variables (100% complete), we trained the model on 75% and validated it on 25% of the patients in order to perform internal validation of the final model. We optimized the model on negative predictive value (NPV) to minimize the likelihood of missing progression. By expert assessment of the test characteristics, including swarm plots of the probability scores, cut-offs were identified for low, intermediate and high risk for disease progression. Results: Of the 492 SSc patients (range of follow-up: 2-10yrs), disease progression during follow-up was observed in 52% (median time 4.9yrs), including myocardial progression in 29%, lung progression in 23%, skin progression in 16%, and death in 12%. Performance of the model in the test set showed an AUC-ROC of 0.66. Probability score cutoffs were defined: low risk for disease progression (<0.197, NPV:1.0; 29% of patients), intermediate risk (0.197-0.223, NPV:0.82; 27%) and high risk (>0.223, NPV:0.78; 44%). The predictive variables included in the model were: previous use of cyclophosphamide or corticosteroids, start with immunosuppressive drugs, previous gastrointestinal progression, previous cardiovascular event, pulmonary arterial hypertension, modified Rodnan Skin Score, creatinine kinase, and diffusing capacity for carbon monoxide. Conclusion: Our machine-learning-assisted model for disease progression enabled us to classify 29% of SSc patients as ‘low risk’. In this group annual assessment programs could be less extensive than indicated by international guidelines. Baseline characteristics Total n=492 Non-Progressors N=235 Progressors N=257 Demographics Female, n (%) 389 (79) 193 (82) 196 (76) Age, mean (SD) 55 (14) 55 (15) 55 (13) Disease duration nonRP, median (IQR) 3.2 (0.9-10.3) 3.5 (0.8-10.5) 3.6 (1.1-9.3) Organ involvement DcSSc, n (%) 118 (24) 34 (15 ) 84 (33 ) DLCO% of pred, mean (SD) 66 (18) 69 (18) 64 (17) FVC% of pred, mean (SD) 98 (23) 96 (24) 97 (21) ILD on HRCT, n (%) 183 (37) 66 (28 ) 117 (46 ) PAH, n (%) 26 (5) 10 (4) 16 (6) GAVE, n (%) 9 (2) 4 (2) 5 (2) Cardiac involvement, n (%) 28 (6) 14 (6) 14 (5) Myositis, n (%) 8 (2) 6 (3) 2 (1) Renal crisis, n (%) 14 (3) 6 (3) 8 (3) Autoantibodies Anti-centromere, n (%) 194 (39) 118 (50 ) 76 (30 ) Anti-topoisomerase, n (%) 116 (24) 42 (18 ) 74 (29 ) RP=raynaud phenomenon, dcSSc= diffuse cutaneous systemic sclerosis, mRSS=modified rodnan skin score, DU=digital ulcera, DLCO= single-breath diffusing capacity for carbon monoxide, FVC= forced vital capacity, ILD=interstitial lung disease, HRCT= high resolution computed tomography, PAH= pulmonary arterial hypertension, GAVE= gastric antral vascular extasia. Disclosure of Interests: None declared

Objective To investigate whether calprotectin (S100A8/A9 or MRP8/14), an inflammatory complex released by monocytes, could indicate residual subclinical inflammation in rheumatoid arthritis (RA) patients who are in stable remission on disease-modifying anti-rheumatic drugs (DMARDs) and serve as a marker for disease flare after DMARD tapering. Methods We used data from two trials. Patients from the IMPROVED study had early (< 2 years) RA, and when they achieved disease activity score remission (DAS44 < 1.6), they stopped methotrexate to attempt drug-free remission. Patients from the RETRO study had established RA in stable remission (DAS28 < 2.6) and either tapered by 50% or stopped (biological or conventional) DMARDs. Circulating calprotectin at the tapering time point was determined by ELISA, and its predictive value for flare (loss of remission) within 12 months of DMARD tapering/stopping was determined. Results In both IMPROVED ( n = 104) and RETRO ( n = 57), patients that flared within 12 months had higher calprotectin at the moment of DMARD tapering/stopping. Twofold higher calprotectin at the moment of DMARD tapering/stopping was associated with an increased risk (odds ratio) of flare of 1.07 (95% CI 0.98–1.18, p = 0.14) in the IMPROVED and 3.62 (95% CI 1.76–7.46, p < 0.001) in the RETRO. Correcting for clinical predictors of flare (DAS at study inclusion, anti-CCP2 positivity, gender) did not change these estimates. The area under the receiver operating curve of calprotectin levels for predicting flare within 12 months was 0.63 (95% CIs 0.51–0.76) in the IMPROVED study and 0.80 (95% CIs 0.69 to 0.92) in the RETRO study. Conclusion Circulating calprotectin levels in RA patients in remission on DMARDs are higher in patients that will flare upon DMARD tapering/stopping. Since the differences between the cohorts precluded definitive conclusions, more research is needed to determine whether calprotectin has prognostic value in predicting flare after attempting drug tapering in RA. Trial registration IMPROVED, ISRCTN11916566 . RETRO, 2009-015740-42 .

Introduction The autoantibody profile of seropositive rheumatoid arthritis (RA) is very diverse and consists of various isotypes and antibodies to multiple post-translational modifications. It is yet unknown whether this varying breadth of the autoantibody profile is clinically relevant and associates with treatment outcomes. Objectives To investigate whether the composition of the autoantibody profile in RA, as a marker of the underlying immunopathology, influences initial and long-term treatment outcomes. Methods In sera of 399 seropositive RA patients in the IMPROVED study1 drawn at baseline and at the moment of drug tapering, we measured IgG, IgM, and IgA isotypes for anti-cyclic citrullinated peptide-2 and anti-carbamylated protein antibodies, IgM and IgA rheumatoid factor, and reactivity against 4 citrullinated and 2 acetylated peptides (anti-modified protein antibodies (AMPAs)). We investigated the effect of the breadth of the autoantibody profile on; change in disease activity score (DAS)–44 between 0 and 4 months, initial drug–free remission (DFR: drug–free DAS44<1.6) achieved between 1 and 2 years of follow–up, and long–term sustained DFR until last follow–up. Results Corrected for age, gender, smoking, BMI, and baseline Health Assessment Questionnaire score, patients with a broad autoantibody profile at baseline had a significantly better early treatment response: ΔDAS 0–4 months of 1–2, 3–4, and 5–6 vs 7–8 isotypes: −1.5 [p<0.001], −1.7 [p=0.003], and −1.8 [p=0.001] vs −2.2. Similar results were observed for AMPA-number; ΔDAS 0–4 months of 1–2, 3–4, and 5–6 vs 7–8 AMPAs, respectively: −1.7 [p=0.016], −1.5 [p<0.001], and −1.9 [p=0.22] vs −2.1. However, patients with a broad baseline autoantibody profile achieved less initial DFR. For long-term sustained DFR there was no longer an association with the breadth of the autoantibody response. When assessing autoantibodies at the moment of tapering, similar results were observed. Conclusions A broad baseline autoantibody profile is associated with a better early treatment response and a worse chance of achieving DFR at early stages, but not later in the treatment regimen, suggesting that the relevance of the autoantibody profile for treatment outcomes diminishes over time. The breadth of the baseline autoantibody profile, reflecting a break in tolerance against several different autoantigens and extensive isotype switching, may indicate a more active humoral autoimmunity which could make the underlying disease processes initially more suppressible by medication. Reference . Heimans. AR&T2016;18:23. Disclosure of interest None declared

ObjectivesTo determine the 5-year outcomes of early remission induction therapy followed by targeted treatment aimed at drug-free remission (DFR) in patients with early arthritis.MethodsIn 12 hospitals, 610 patients with early (<2 years) rheumatoid arthritis (RA) or undifferentiated arthritis (UA) started on methotrexate (MTX) 25 mg/week and prednisone (60 mg/day tapered to 7.5 mg/day). Patients not in early remission (Disease Activity Score <1.6 after 4 months) were randomised (single blind) to arm 1, adding hydroxychloroquine 400 mg/day and sulfasalazine 2000 mg/day, or arm 2, switching to MTX plus adalimumab 40 mg/2 weeks. Treatment adjustments over time aimed at DFR. Outcomes were remission percentages, functional ability, toxicity and radiological damage progression after 5 years.ResultsAfter 4 months, 387 patients were in early remission, 83 were randomised to arm 1 and 78 to arm 2. After 5 years, 295/610 (48%) patients were in remission, 26% in sustained DFR (SDFR) (≥1 year) (220/387 (57%) remission and 135/387 (35%) SDFR in the early remission group, 50% remission, 11% SDFR in the randomisation arms without differences between the arms). More patients with UA (37% vs 23% RA, p=0.001) and more anticitrullinated protein antibody (ACPA)-negative patients (37% vs 18% ACPA-positive, p<0.001) achieved SDFR.Overall, mean Health Assessment Questionnaire was 0.6 (0.5), and median (IQR) damage progression was 0.5 (0–2.7) Sharp/van der Heijde points, with only five patients showing progression >25 points in 5 years.ConclusionsFive years of DFR-steered treatment in patients with early RA resulted in almost normal functional ability without clinically relevant joint damage across treatment groups. Patients who achieved early remission had the best clinical outcomes. There were no differences between the randomisation arms. SDFR is a realistic treatment goal.

OBJECTIVES:To compare outcomes of targeted treatment aimed at either low disease activity or remission in patients with early active rheumatoid arthritis (RA).METHODS:Five-year outcomes were compared in 133 patients with early active RA (1987), starting with methotrexate, sulfasalazine and tapered high dose of prednisone (arm 3 of the BehandelStrategieën (Treatment Strategies for Rheumatoid Arthritis) (BeSt) study), targeted at Disease Activity Score (DAS) ≤2.4 (low disease activity), and 175 patients with early RA, starting methotrexate and tapered high dose of prednisone, targeted at DAS <1.6 (selected from IMPROVED study who would have fulfilled inclusion criteria of the BeSt study). Association of treatment target with outcomes DAS <1.6, Boolean remission at year 1 and drug-free DAS remission (DFR) at year 5 were analysed by logistic regression analysis.RESULTS:At baseline, DAS <1.6 steered patients had a milder disease than DAS ≤2.4 steered patients (mean DAS 4.1±SD 0.7vs4.4±0.9, p=0.012) and less radiological damage. DAS decrease, functional ability and radiological damage progression over time were similar in both patient groups. DAS ≤2.4 was achieved in similar percentages in both patient groups, but more DAS <1.6 steered patients achieved DAS <1.6 and DFR. DAS <1.6 steered treatment was associated with achieving DAS <1.6 (OR 3.04 (95% CI 1.64 to 5.62)) and Boolean remission (3.03 (1.45 to 6.33)) at year 1 and DFR at year 5 (3.77 (1.51 to 9.43)).CONCLUSIONS:In patients with early active RA who start with comparable disease-modifying antirheumatic drug+prednisone combination therapy, subsequent DAS <1.6 steered treatment is associated with similar clinical and radiological outcomes over time as DAS ≤2.4 steered treatment; however, in the DAS <1.6 steered group, more patients achieved remission and drug-free remission.

Background Foot problems developing during the disease course of rheumatoid arthritis (RA) patients can cause decreased mobility and quality of life. Orthopedic shoes may help to reduce pain and increase activity participation in RA patients. Objectives To investigate if foot damage due to RA can predict if patients will wear orthopedic shoes within 10 years after treatment start. Methods In the four treatment arms of the BeSt study, 508 patients with recent onset RA were treated to target (disease activity score (DAS) ≤2.4). After 10 years, patients were asked if they used orthopedic shoes. Univariable binary logistic regression was performed with orthopedic shoe use as outcome variable and baseline total Sharp/van der Heijde score (SHS), foot erosions and foot joint space narrowing (JSN) as continuous and binary variables (score >0.5 yes/no) as potential predictors. Next, rheumatoid factor (RF), smoking (yes/no), anti-citrullinated protein antibodies (ACPA), DAS and age were simultaneously added as predictors in a multivariable model, in combination with the statistically significant predictors (p<0.1) from the univariable regression. Only predictors with statistically significant contribution were kept in the final model. Interaction of each predictor with treatment arm was tested. Results Of 285/508 patients (56.1%) information was available regarding orthopedic shoe use. Responders were younger than non-responders [age mean (SD) 51.3 (12.0) vs 58.4 (14.8) years, p<0.001], but did not differ statistically significant in gender, smoking status, DAS, SHS, JSN or erosions (all at baseline). Twenty percent (57/273) of the patients reported orthopedic shoes use after 10 years [68.4% female, mean (SD) age 50.3 (11.0) years, DAS 4.6 (0.9), SHS 4.7 (5.3), erosions 1.0 (2.3), JSN 1.0 (1.9), ACPA+ 83.3%, RF+ 77.2%, all at baseline]. Orthopedic shoe users were more often ACPA+ (77.2% vs. 65.8%) and had more erosions [mean (SD) 1.25 (2.43) vs. 0.48 (2.48), all p<0.05]. No predictor had a significant interaction with allocated treatment group. Univariable logistic regression showed that only foot erosions had a significant contribution to the model as binary variable (OR 1.95), but not as continuous variable (OR 1.06). Neither total SHS nor foot-JSN (binary or continuous) contributed significantly to the model (OR 1.61 and 1.03 for SHS; 1.59 and 1.08 for foot-JSN, respectively). Multivariable logistic regression showed that baseline presence of foot erosions (binary; OR 1.85), ACPA+ (OR 4.88) and DAS (OR 1.72) were independent predictors of orthopedic shoe use after 10 years. Combining foot erosions (binary; OR 1.87), ACPA (OR 4.46) and DAS (OR 1.73) resulted in the best model (see table 1). Conclusions Despite 10 years of DAS ≤2.4 targeted treatment, 20% of recent onset RA patients with available data after 10 year used orthopedic shoes. Presence of foot erosions at treatment start predicts the use of orthopedic shoes after 10 years. The risk of orthopedic shoe use increases for ACPA+ patients and to a lesser extent for patients with higher baseline DAS. Disclosure of Interest S. Bergstra: None declared, R. van den Berg: None declared, C. Bijkerk: None declared, A. Gerards: None declared, R. Goekoop: None declared, P. Kerstens: None declared, W. Lems: None declared, T. Huizinga: None declared, R. Landewé: None declared, C. Allaart Grant/research support from: The study was designed by the investigators and supported by a government grant from the Dutch Insurance Companies, with additional funding from Schering-Plough B.V. and Janssen B.V. Data collection, trial management, data analysis and preparation of the manuscript were performed by the authors.

Background In patients with established RA, radiological progression is preceded by metacarpal bone mineral density (mBMD) loss. Objectives To assess whether in early (rheumatoid) arthritis patients, mBMD loss after 4 months is an independent predictor for radiological progression after 1 year of antirheumatic treatment. Methods mBMD was measured in metacarpals 2-4 by digital X-ray radiogrammetry (DXR) in patients participating in the IMPROVED study, a single blind multicenter study in 479(79%) RA (2010 ACR/EULAR criteria, symptom duration < 2 years) and 122(20%) UA (arthritis >1 joint, at risk for developing RA by rheumatologists estimation but not fulfilling the 2010 criteria) patients. All patients started treatment with 4 months of methotrexate (MTX) and a tapered high dose of prednisone, followed by tapering or adjusting treatment aiming at DAS <1.6. We performed univariable logistic regression with radiologic progression (increase in total Sharp-van der Heijde Score (tSHS) ≥0.5 after 1 year) as dependent variable and mBMD loss after 4 months and other known predictors as covariates. For power reasons, we selected those two univariable predictive variables (p-value ≤0.10) with the lowest p-value for multivariate regression. Results Of 237 patients (43(18%) UA, 192(81%) RA, 2 missing classification) mBMD measurements at baseline and 4 months and radiological progression data after 1 year were available. Median mBMD loss after 4 months (4mo-mBMD loss, mg/cm2 unless indicated otherwise) was 2.3(-1.7 to 6.8) (corresponding to 0.6(-0.4 to 1.7) mg/cm2/month). Seventeen (7%) patients had radiological progression after 1 year and 220(93%) had not. Patients with radiological progression had a median (IQR) 4mo-mBMD loss of 5.5(2.7 to 13.6) compared to 2.0(-2.0 to 6.6) in patients without progression (corresponding to 1.4(0.7 to 3.4) and 0.5(-0.5 to 1.6) mg/cm2/month), (p=0.002). Univariable predictors for progression (OR (95%CI) were age (1.0(1.0-1.1)), fulfilling the 2010 criteria for RA (6.4(0.9-48)), postmenopausal status (6.2(1.4-27)), ESR (1.0(0.999-1.0)), tSHS (1.1(0.996-1.1)), presence of erosions (4.4(2.0-10.0)) and presence of ACPA (3.5(1.3-9.4)), all at baseline, and 4mo-mBMD loss (mg/cm2/months) (1.5(1.2-1.9)). Female gender, RF positivity, symptom duration, baseline swollen and tender joint counts were not predictive. Independent predictors for progression after 1 year were presence of baseline erosions (5.2(1.7-16)) and 4mo-mBMD loss (mg/cm2/month) (1.5(1.1-2.0)). In 203(86%) patients who had no erosions at baseline, 4mo-mBMD loss (mg/cm2/month) was the only independent predictor for progression after 1 year (1.8(1.3-2.7), adjusted for age). Conclusions In early (rheumatoid) arthritis patients, mBMD loss after 4 months of MTX and prednisone is an independent predictor for radiological joint damage progression, despite the fact that radiological progression was only present in 7% of patients after 1 year of a remission steered treatment strategy. In particular in patients who are non-erosive at baseline, mBMD loss after 4 months may help to steer treatment decisions as predictor of damage progression. Disclosure of Interest None Declared