Conventional DMARDs Research Articles

Comparative effectiveness of antitumour necrosis factor agents, biologics with an alternative mode of action and tofacitinib in an observational cohort of patients with rheumatoid arthritis in Switzerland

BackgroundMultiple biologic and targeted synthetic disease-modifying rheumatic drugs (b/tsDMARDs) are approved for the management of rheumatoid arthritis (RA), including TNF inhibitors (TNFi), bDMARDs with other modes of action (bDMARD-OMA) and...

Effectiveness and safety of biologic and targeted synthetic disease-modifying anti-rheumatic drugs in elderly patients with rheumatoid arthritis: real-world data from the KOBIO Registry

We aimed to evaluate the clinical outcomes and safety of biologic and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) and to identify predictors of treatment responses to b/tsDMARDs in elderly patients with rheumatoid arthritis (RA). Data from the nationwide cohort of elderly (≥ 65 years) patients enrolled in the KOBIO Registry were analysed. Clinical outcomes were assessed, including changes in the Simplified Disease Activity Index, after treatment. Adverse events and reasons for drug discontinuation were assessed. Multivariable logistic regression analyses were performed to determine which baseline variables affected treatment responses and adverse events (AE). Elderly patients treated with b/tsDMARDs (n=355) or conventional synthetic DMARDs (csDMARDs) (n=104) were included. The median age was 70 years and 77% were female. After 1 year, 63% of patients in the b/tsDMARD group and 68% in the csDMARD group achieved remission or low disease activity (LDA). Overall, 27% of patients in the b/tsDMARDs group and 24% in the csDMARDs group experienced AE. A total of 43.4% of patients on b/tsDMARDs discontinued therapy due to lack of effectiveness (27%), AE (34%), or other reasons (35%). The estimated median retention of b/tsDMARDs was 2.5 years. Male sex and non-exposure to tobacco at baseline were independent factors associated with achieving remission or LDA after 1 year. Interstitial lung disease (ILD) was the most prominent comorbidity associated with AE. Treatment with b/tsDMARDs is effective and well tolerated in elderly patients with RA; nonetheless, ILD is a key comorbidity that should be monitored carefully.

Depression in Psoriatic Arthritis: Dimensional Aspects and Link with Systemic Inflammation.

Studying comorbidities in patients with psoriatic arthritis (PsA) provides a better understanding of the extended burden of the disease. Depression and anxiety are well recognized but understudied comorbidities in patients with PsA. The prevalence of depression is significantly higher in this patient population than in the general population, with far reaching consequences in terms of long-term quality of life. Over the past few years there has been an increasing interest in the link between inflammation and depression, with several novel studies being conducted. Recent evidence suggests a significant improvement of depression in PsA patients treated with biologic disease-modifying anti-rheumatic drugs (bDMARDs) as compared to conventional DMARDs. Depression in PsA is multidimensional, with recognized phenotypes, including cognitive disorder, alexithymia and anhedonia. The paucity of standardized, validated tools to screen these dimensional phenotypes remains an unmet need. Prevalence studies on depression in patients with PsA, mostly based on patient-reported outcomes, are only able to highlight the tip of the iceberg. A comprehensive, multi-disciplinary approach addressing the subdomains of depression is imperative for a better understanding of depression in PsA patients, as well as to find a way forward for improving their quality of life. In this scoping review, we explore existing evidence on the burden of depression in PsA patients, the link between inflammation and depression in these patients and the screening tools used to evaluate the subdomains of depression.

Rheumatic disease and COVID-19: initial data from the COVID-19 Global Rheumatology Alliance provider registries.

Author(s): Gianfrancesco, Milena A; Hyrich, Kimme L; Gossec, Laure; Strangfeld, Anja; Carmona, Loreto; Mateus, Elsa F; Sufka, Paul; Grainger, Rebecca; Wallace, Zachary; Bhana, Suleman; Sirotich, Emily; Liew, Jean; Hausmann, Jonathan S; Costello, Wendy; Robinson, Philip; Machado, Pedro M; Yazdany, Jinoos; COVID-19 Global Rheumatology Alliance Steering Committee

Similarities in clinical course and outcome between juvenile idiopathic arthritis (JIA)-associated and ANA-positive idiopathic anterior uveitis: data from a population-based nationwide study in Germany

BackgroundTo analyze whether ANA-positive idiopathic anterior uveitis differs from JIA-associated uveitis concerning clinical course, response to treatment, and disease outcome.MethodsProspective study of the National Paediatric Rheumatological Database (NPRD) including its uveitis add-on module from the years 2002 to 2016. Cross-sectional data from the years 2002 to 2016 were analyzed. Patients with JIA-associated uveitis and with ANA-positive idiopathic anterior uveitis were included and the disease manifestation investigated in terms of uveitis characteristics and disease course.ResultsOf the total cohort of 34,458 patients enrolled in the NPRD, including 3551 patients with uveitis, those with detailed uveitis documentation were taken into account: 62 ANA-positive patients with idiopathic anterior uveitis (group 1), 688 patients with initial uveitis diagnosis after JIA onset (group 2), and 61 JIA patients with initial uveitis diagnosis before arthritis onset (group 3). Anterior uveitis was documented in 100%, 94%, and 80% of patients and with insidious onset of uveitis flare in 50%, 70.9%, and 56.1% each in groups 1, 2, and 3, respectively. Use of topical or systemic corticosteroids and conventional synthetic or biological DMARDs did not significantly differ between the patient groups, either at the initial or the 2-year follow-up (2-FU) visits (mean 2 years, each p > 0.05). At 2-FU, uveitis inactivity was achieved in 64.7%, 55.8%, and 61.5% of patients in groups 1, 2, and 3 (p > 0.05). Uveitis-related complications were more frequent at the initial visit and at 2-FU in groups 1 and 3, as compared to group 2.ConclusionsANA-positive idiopathic uveitis and JIA-associated uveitis do not significantly differ concerning clinical course of uveitis, treatment, and response to corticosteroids and DMARDs.

Favorable retention rates and safety of conventional anti-rheumatic drugs in older patients with rheumatoid arthritis.

Physicians are challenged by the recognition and treatment of older patients with rheumatoid arthritis (RA). The aim of this case-control study was to evaluate the retention and safety of conventional disease-modifying anti-rheumatic drugs in older patients with RA.In this observational case-control study, we assessed older patients with RA (≥65 years) who were diagnosed in 3 different rheumatology centers from Turkey. Patients were divided as to those aged ≥65 years (elderly rheumatoid arthritis [ERA]) and those aged <65 years (young rheumatoid arthritis [YRA]) at the time of conventional DMARD treatment initiation. The Mann-Whitney U test was used for the comparison of 2 non-normally distributed groups. The Chi-square (χ2) test was used for categorical variables. Survival analysis were performed using the Kaplan-Meier method.Four hundred eighteen patients with RA (296 females [71%]) were included from January 2010 to January 2018. The age of treatment onset of 190 (47%) patients was in the elderly period and they were included in the ERA group. In the analysis of drug retention rates, there was no significant difference between the ERA and YRA groups for each conventional DMARD (methotrexate 71.2% in ERA, 62.7% in YRA, P = .817; hydroxychloroquine 82.9% in ERA, 78.8% in YRA, P = .899; leflunomide 81.4% in ERA, 84.4% in YRA, P = .205; sulfasalazine 37.5% in ERA, 40.9% in YRA, P = .380). The adverse event data were also similar in both groups.The drug retention and adverse effect rates in older patients with RA using conventional DMARDS are similar to the rates in young patients with RA.

EP43 Biologic retention in psoriatic arthritis: a real world study

Abstract Background Biologics have led to a sea change in the management of psoriatic arthritis (PsA) with unprecedented improvement in the signs, symptoms and radiographic damage, resulting in improvement in functionality and quality of life. However longitudinal data for their retention and tolerability is sparse. Our objective was to evaluate real-world biologic therapy duration and reasons for discontinuing treatment. Methods We conducted a retrospective analysis of our PsA electronic register from 1994 up to and including April 2019 at our university teaching hospital. We had access to full patient records including details on co-morbidities, drugs and disease management. Results 335 patients were identified with PsA. 58% were female with mean age 46 yr (13-81). 113 (33.7%) patients had been treated with a biologic with 105 (93%) continuing at the time of analysis. 60 individuals were prescribed combination therapy with DMARDs. Mean age was 43.3 (13-81) with 56% women. The biologics sample was ethnically diverse including 80% White Caucasian patients, 17% Asian and others (3%). Significant co-morbidities included cardiovascular disease (18.6%) and diabetes (4.4%). Eight different biologics were in use with adalimumab being the most prescribed (67%). 35 (30.9%) patients had stopped biologics at some point with 76 episodes of cessation. 6% of our sample had discontinued two or more biologic treatments. The mean duration before biologic therapy was discontinued was 18.2 months (8 days to 9.5 years), which was almost twice as long as the average period before discontinuing a DMARD (9.9 months). Main reasons for stopping treatment included 23% each due to GI symptoms, neurological causes, cutaneous symptoms and other side effects. The remaining 8% reported fatigue as the reason for stopping therapy. Conclusion To our knowledge this is the first dedicated retrospective review of a large real world PsA cohort comparing drug survival and tolerability of biologics against DMARDs. Biologic therapies are well tolerated in psoriatic arthritis. There is no significant difference amongst various modes of action. Over a quarter of the patients discontinue the drug owing to intolerance with mean drug survival of 18 months. In contrast nearly two-thirds were intolerant of DMARDs and stopped within ten months. Thus both the rate and duration of biologic retention is significantly better than conventional DMARDs. This has significant economic impact as NICE guidelines require an adequate trial of two DMARDs for six months prior to advanced therapy. However, this approach is unlikely to be cost effective as the disease progresses whilst patients struggle with DMARDs prescription and thus delay biologics which are more likely to be tolerated and retained longer. Hence there is an urgent need to review NICE guidelines to allow earlier employment of biologics in the treatment paradigm with significant benefits to both patients and the health economy. Disclosures: I. Jawad: None. M.K. Nisar: None.

P204 Effect of baricitinib on functional impairment in RA patients with moderate disease activity and an inadequate response to conventional DMARDs

Abstract Background In RA, disease activity correlates with physical function and there is a link between joint damage and functional disability. In many countries, RA patients with inadequate response (IR) to MTX or other conventional DMARDs (cDMARDs) are not eligible for potentially more effective treatments, such as biologic or targeted synthetic DMARDs (tsDMARDs), unless they have high disease activity (HDA). Thus, managing RA patients with persistent moderate disease activity (MDA) despite cDMARD treatment poses a problem. Baricitinib (BARI) is a tsDMARD approved for the treatment of moderate to severe RA in adults. This post-hoc analysis assessed if RA patients with MDA benefit from improved physical function with BARI treatment to the same extent as patients with HDA. Methods Patients analysed were from the modified intention-to-treat populations in the BARI phase 3 studies RA-BEAM (MTX-IR) and RA-BUILD (cDMARD-IR) with moderate to severe disability (HAQ-Disability Index [HAQ-DI] score ≥1), MDA (Simplified Disease Activity Index [SDAI] score 11.1-26.0) or HDA (SDAI score&amp;gt;26.0) and non-missing SDAI data at baseline. All patients fulfilled ACR criteria for RA. Patients from RA-BEAM received BARI 4 mg + MTX once daily (n = 396), adalimumab 40 mg every 2 weeks + MTX (n = 270) or placebo (PBO) + MTX (n = 390); patients from RA-BUILD received BARI 4 mg (n = 189) or 2 mg (n = 186) or PBO (n = 185). Multivariable linear regression (MLR) models were used to estimate mean HAQ-DI scores at baseline and week 24 (W24) for the treatment arms stratified by baseline disease activity (MDA or HDA SDAI). Age, RA duration, BMI, high-sensitivity CRP, baseline SDAI disease activity (MDA/HDA), treatment and treatment-by-baseline SDAI interaction were included as covariates. The MLR model for HAQ-DI at (W24) was further adjusted by baseline HAQ-DI. Results In patients from RA-BEAM with MDA at baseline, the mean adjusted HAQ-DI score at W24 was greater in PBO (1.314) than in BARI 4 mg (0.843) patients (Δ = 0.472; p = 0.001). A similar pattern of improved physical function with BARI was seen in RA-BUILD, but the adjusted mean difference in HAQ-DI score between PBO (1.376) and BARI 4 mg (1.113) was not statistically significant (Δ = 0.263; p = 0.109). In patients with HDA at baseline, the W24 mean adjusted HAQ-DI score was 0.443 points greater (p &amp;lt; 0.001) with PBO (1.387) than with BARI 4 mg (0.944) in RA-BEAM, and 0.257 points greater (p &amp;lt; 0.001) in RA-BUILD. Conclusion MTX-IR and/or cDMARD-IR RA patients with MDA and moderate to severe disability at baseline treated with BARI showed a similar pattern of improvement in physical function vs. PBO-treated patients to that seen in patients with HDA, supporting early use of BARI in MDA patients. As for those with HDA, patients with persistent MDA despite MTX and/or other cDMARD treatment could benefit from access to biologic and tsDMARDs to prevent disability progression. Disclosures B. Kirkham: Consultancies; AbbVie, Eli Lilly, Gilead, Janssen, Novartis, Pfizer. Grants/research support; Eli Lilly, Novartis. E. Nikiphorou: Honoraria; Pfizer, Sanofi, Gilead, Celltrion, Eli Lilly. P. López-Romero: Shareholder/stock ownership; Eli Lilly. Other; Full time employee of Eli Lilly. I. Kouris: Shareholder/stock ownership; Eli Lilly. Other; Full time employee of Eli Lilly. T. Holzkaemper: Shareholder/stock ownership; Eli Lilly. Other; Full time employee of Eli Lilly. L. Zaremba-Pechmann: Other; contractor for Eli Lilly and Company. I. de la Torre: Shareholder/stock ownership; Eli Lilly. Other; Full time employee of Eli Lilly. P.C. Taylor: Consultancies; AbbVie, Biogen, Galapagos, Gilead, GlaxoSmithKline, Janssen, Eli Lilly, Pfizer, Roche, Sanofi, Nordic Pharma, Fresenius, UCB. Grants/research support; Celgene, Galapagos, Janssen, Eli Lilly.

P209 Safety profile of upadacitinib in rheumatoid arthritis: integrated analysis from the select Phase 3 clinical programme

Abstract Background Upadacitinib (UPA), a JAK1-selective inhibitor, significantly improved clinical signs and symptoms of rheumatoid arthritis (RA) in patients naïve to methotrexate (MTX) and with an inadequate response to conventional synthetic DMARDs (csDMARD-IR) or biologic DMARDs (bDMARD-IR). The objective was to assess the safety of UPA as monotherapy (mono) and as combination therapy with background csDMARDs in patients with moderately to severely active RA from the safety database of the Phase 3 clinical programme. Methods Treatment-emergent adverse events (TEAEs) from 5 pivotal, randomised, double-blind, controlled Phase 3 trials of UPA 15 mg or 30 mg QD in RA patients were analysed using integrated short-term (ST), individual studies with long-term (LT) active comparator and integrated LT (all Phase 3 exposure; E/100PY) analyses sets. Results Across the Phase 3 trials, 3834 patients received ∼1 dose of UPA 15 mg (n = 2630) or 30 mg QD (n = 1204) »4020.1 PY of UPA exposure with no option to switch doses. The ST frequencies of overall SAEs and AEs leading to discontinuation were low, but higher on both UPA doses vs PBO. LT event rates were similar on UPA 15 mg vs ADA and slightly higher on UPA vs MTX mono. Deaths occurred in all treatment groups. Serious infection (SIEs) frequencies were higher on both UPA doses vs PBO. SIE rates on both UPA doses were higher vs MTX, but similar on UPA 15 mg vs ADA. Herpes zoster (HZ) frequencies and rates were higher on both UPA doses vs PBO, and vs MTX, ADA, respectively. The rates of SIE and HZ were higher on UPA 30 vs 15 mg. Adjudicated MACE were reported in all treatment groups including PBO. LT MACE rates were similar on UPA 15 mg and ADA and on UPA 15 mg and MTX mono, but higher on UPA 30 mg mono (low number of events, 2-4 per set). Adjudicated VTEs occurred at comparable frequencies on UPA vs PBO and at comparable rates on UPA vs active comparators. Malignancy (excluding non-melanoma skin cancer [NMSC]) rates were similar on UPA vs MTX, UPA 15 mg vs ADA, and 15 vs 30 mg. The NMSC rates on UPA 15 mg and ADA were similar; the rate on 30 mg was higher than 15 mg, but both UPA NMSC rates were in the range reported for RA patients treated with DMARDS. The standardised incidence ratio (95% CI) for malignancy (15 mg: 0.98 [0.61, 1.49], 30 mg: 1.49 [0.85, 2.42]) was not elevated vs the general population. Conclusion Treatment with UPA increased the risk of SIE and HZ, but not those of VTE, MACE, and malignancy vs comparators. These data support that UPA has an acceptable safety profile in the treatment of moderately to severely active RA. Disclosures S.B. Cohen: Grants/research support; Received grants and personal fees from Amgen, Abbvie, Boehringer Ingelheim, Pfizer and Sandoz. R. van Vollenhoven: Consultancies; AbbVie, AstraZeneca, Biotest, Bristol-Myers Squibb, Celgene, GSK, Janssen, Lilly, Medac, Merck, Novartis, Pfizer, Roche, and UCB. Grants/research support; Received grants from AbbVie, Arthrogen, Bristol-Myers Squibb, GlaxoSmithKline (GSK), Lilly, Pfizer, and UCB. K. Winthrop: Consultancies; Received consulting fees and research grants from UCB Pharma, Pfizer, Bristol-Myers Squibb, Eli Lilly, AbbVie, and Roche. C. Zerbini: Consultancies; Merck, Pfizer, Sanofi-Aventis and Pfizer. Grants/research support; Received research grants from Amgen, GSK, Lilly, Merck, Novartis, Pfizer, Sanofi-Aventis, Servier and Roche. Y. Tanaka: Honoraria; Daiichi-Sankyo, Astellas, Eli Lilly, Chugai, Sanofi, Abbvie, Pfizer, YL Biologics, Bristol-Myers, Glaxo-Smithkline, UCB, Mitsubishi-Tanabe, Novartis, Eisai, Takeda, Janssen, Asahi-kasei. Grants/research support; Mitsubishi-Tanabe, Bristol-Myers, Eisai, Chugai, Takeda, Abbvie, Astellas, Daiichi-Sankyo, Ono, MSD, Taisho-Toyama. L. Bessette: Grants/research support; Speaking fees, consulting fees, and research grants from Amgen, BMS, Janssen, Roche, UCB Pharma, AbbVie Inc, Pfizer, Merck, Celgene, Sanofi, Eli Lilly, and Novartis. Y. Zhang: Corporate appointments; Employee of AbbVie. N. Khan: Corporate appointments; Employee of AbbVie. B. Hendrickson: Corporate appointments; Employee of AbbVie. J.V. Enejosa: Corporate appointments; Employee of AbbVie. G. Burmester: Honoraria; Received speaking or consulting fees from AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma.

P216 Effects of filgotinib on anaemia, thrombocytopoenia and leukopoenia: results from a Phase 3 study in patients with active RA and prior inadequate response or intolerance to bDMARDs

Abstract Background Cytopoenias are common in patients treated for rheumatoid arthritis (RA) with non-janus kinase 1 (JAK1)-selective inhibitors, possibly due to JAK2-mediated haematopoietic growth factor inhibition. We investigated the extent of cytopoenia in patients with active RA, despite prior treatment with biological disease-modifying antirheumatic drugs (bDMARDs), treated with the JAK1-selective inhibitor filgotinib (FIL), in a Phase 3 trial (FINCH2; NCT02873936). Methods In the double-blind, Phase 3 FINCH2 trial, patients were randomised 1:1:1 to receive oral FIL 200mg, 100mg, or placebo (PBO) once daily for 24 weeks (W) + conventional synthetic DMARDs. We assessed shifts from baseline at 12 and 24 weeks in haemoglobin, platelets, neutrophils and lymphocytes. Results 448 patients were treated: FIL 200mg, n = 147; FIL 100mg, n = 153; PBO, n = 148. Overall, haemoglobin, platelet, lymphocyte and neutrophil levels remained consistent throughout the study. At baseline, 129 (28.8%), 4 (0.9%), 10 (2.2%) and 26 (5.8%) patients had mild-moderate low levels of haemoglobin, platelets, neutrophils and lymphocytes, respectively, and 5 (1.1%) had severely low levels of lymphocytes. Of the patients with mild-moderate low haemoglobin levels at baseline, 10-13% achieved normal levels by W24 vs 8% receiving PBO (Table). Of those with normal baseline haemoglobin levels, 6-10% had mild low levels at W24. All patients with baseline mild-moderate low platelets and neutrophils had normal levels at W24, except one patient with mild neutropoenia receiving FIL 100mg. Of the patients with normal platelet and neutrophil levels at baseline, &amp;gt;94% maintained these at W24 in all treatment groups. By W24, 3.2%, 5.2% and 2.2% of patients treated with FIL 200mg, FIL 100mg and PBO, respectively in the baseline mild-moderate subgroup and 1.7% in the severe subgroup treated with FIL 100mg had normal lymphocyte counts. Conclusion In this study, most patients in the baseline normal cell count subgroups maintained this status over 24 weeks of FIL treatment. Of the patients with mild-to-moderately low haemoglobin at baseline, &amp;gt;9% shifted towards haemoglobin normalisation. Similar patterns of improvement from baseline were observed for platelet, lymphocyte and neutrophil counts. FIL appears not to increase the incidence of cytopenias in patients with active RA despite prior biologic therapies. Disclosures D. Walker: Other; Received support from Lilly, Pfizer, Novartis, Roche. M.C. Genovese: Other; Received support from Gilead Sciences Inc., Galapagos NV, AbbVie Inc. Eli Lilly and Company, Pfizer. K. Kalunian: Grants/research support; Grand support from Gilead. J. Gottenberg: None. B. Bartok: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. Y. Tan: Corporate appointments; Employee of Gilead Sciences, Inc... Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. Y. Guo: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. C. Tasset: Other; Employee of Galapagos. J.S. Sundy: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. K. de Vlam: None. T. Takeuchi: None.

P261 Continuing versus withdrawing ixekizumab in patients with PsA who achieved sustained minimal disease activity: results from the SPIRIT-P3 study

Abstract Background This study evaluated efficacy and safety of continuing vs. withdrawing ixekizumab (IXE), an IL-17A antagonist, in psoriatic arthritis (PsA) patients who achieved sustained minimal disease activity (MDA) on IXE and re-treating with IXE if required. Methods SPIRIT-P3 (NCT02584855) was a multicentre phase 3b study enrolling biologic-naïve patients with active PsA (diagnosis for ≥6 months, meeting classification criteria for psoriatic arthritis, ≥3/68 tender joints, ≥3/66 swollen joints) and previous inadequate response to conventional synthetic DMARDs (csDMARDs). Patients entered a 36-week, open-label (OL) treatment period with IXE every 2 weeks. Between Weeks 36-64, patients were randomised 1:1 to IXE or placebo (PBO) at the visit for which randomisation criteria were met (sustained MDA for at least 4 visits over 3 consecutive months) and evaluated up to Week 104. Patients not meeting randomisation criteria by Week 64 continued IXE up to Week 104. Maintenance of treatment response was measured by time to loss of sustained MDA (relapse) during randomised withdrawal (RW) period. The proportion of patients who relapsed during the first 40 weeks of RW period and time to regain MDA after re-treatment with IXE in relapsed patients were assessed. The Kaplan-Meier product limit method was used to estimate survival curves for time-to variables. Treatment comparisons were performed using a log-rank test adjusting for geographic region and csDMARD use as factors. Cumulative proportion of relapse was analysed using a logistic regression model with treatment, geographic region, and csDMARD use as factors. Safety data were summarised for the entire study period for patients who received ≥1 dose of IXE. Results In total, 394 patients entered the OL treatment period; 158 (40%) achieved sustained MDA criteria and were randomised to IXE (N = 79) or PBO (N = 79). Baseline characteristics were similar between groups. Time to relapse on PBO was significantly shorter than for IXE (p &amp;lt; 0.001) during RW period, with a median time to relapse of 22.3 weeks in the PBO group. The cumulative relapse rate during the first 40 weeks of RW period was 73% for PBO vs. 34% for IXE (p &amp;lt; 0.001). Of those who relapsed on PBO, 96% regained MDA following re-treatment with IXE. The median time to regain MDA was 4.1 weeks (95%CI 4.14-4.29) for PBO and 4.7 weeks (95%CI 4.14-8.29) for IXE. Safety data were consistent with previous IXE PsA studies with no unexpected safety signals. Conclusion Continued IXE therapy was superior to PBO in maintaining MDA in biologic-naïve PsA pts who achieved sustained MDA on initial IXE treatment. A vast majority of patients who lost MDA after IXE withdrawal regained MDA with IXE re-treatment. Continuous IXE treatment is optimal for maintaining MDA; however, patients can regain MDA after re-treatment with IXE in case of treatment interruption. Disclosures L.C. Coates: Corporate appointments; L. Coates is a consultant for: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly and Company, Janssen, MSD, Novartis, Pfizer, Prothena, Sun Pharma, and UCB. Consultancies: L. Coates is a consultant for: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly and Company, Janssen, MSD, Novartis, Pfizer, Prothena, Sun Pharma, and UCB. S.G. Pillai: Corporate appointments; S.G.P. is an employee and shareholder of Eli Lilly and Company. L. Zhang: Corporate appointments; Employee and shareholder of Eli Lilly and Company. D. Adams: Corporate appointments; Employee and shareholder of Eli Lilly and Company. L. Kerr: Corporate appointments; Employee and shareholder of Eli Lilly and Company. M. Hojnik: Corporate appointments; Employee and shareholder of Eli Lilly and Company. G. Gallo: Corporate appointments; Employee and shareholder of Eli Lilly and Company. I. Valter: None. H. Tahir: Grants/research support; H. Tahir has received grants/research support from: AbbVie, Celgene, Eli Lilly and Company, Janssen, and Novartis. V. Chandran: Grants/research support; V. Chandran has received grant/research support from AbbVie, is a consultant for: AbbVie, Amgen, Celgene, Eli Lilly and Company, Janssen, Novartis, Pfizer, and UCB. P. Mease: Consultancies; P. J. Mease is a consultant for and has received grant/research support from: AbbVie, Amgen, BMS, Celgene, Crescendo, Eli Lilly and Company, Genentech, Janssen, Merck, Novartis, Pfizer, UCB, is on the. A. Kavanaugh: Consultancies; A. Kavanaugh is a consultant for Eli Lilly and Company.

P62 Assessing the effect of increased body mass on response to DMARD treatment in rheumatoid arthritis: results from the METEOR database

Abstract Background Worldwide, &amp;gt;60% patients with rheumatoid arthritis (RA) are overweight/obese (body mass index, BMI≥25kg/m2). Studies demonstrate poorer disease outcomes and health-related quality of life in these patients. However, little is known about the effect of increased BMI on drug choice, dosing, or treatment response. Objective: To explore the effect of increased BMI on DMARD-prescribing, methotrexate (MTX)-dose, and disease activity over 12 months. Methods Participants registered on METEOR (international database of RA patients) were stratified into early (&amp;lt;1year post-diagnosis, eRA), and established RA (estRA). EULAR response and DAS28 remission (including components), and treatment regimens were recorded at baseline, 6, and 12 months. Increased BMI (defined overweight and obese) were explored in 1) eRA and 2) estRA, as predictors of good EULAR response, DAS28 remission, number of DMARDs prescribed, and MTX-dose. Logistic and linear regression models (controlling for age, gender, smoking, and baseline outcome values), subgroup analyses (by drug exposure), and sensitivity analyses, were performed. Results 1,313 patients (1056 female) were included, 582 eRA. In eRA, increased BMI was not significantly associated with remission outcomes. In estRA, obese patients on monotherapy were statistically significantly less likely to achieve good EULAR response [OR 0.4 (95%CI 0.23-0.7)] or DAS28 remission [OR 0.47 (95%CI 0.24-0.88)] at 6 months, compared to those of normal weight. A similar trend observed at 12 months did not reach significance. Obese estRA patients were more likely to be treated with combination conventional synthetic DMARDs (csDMARD) than monotherapy, compared with those of normal weight, significant at 6 months [OR 1.59 (95%CI 1.03-2.45)]. In early and established disease, no significant difference in remission outcomes was demonstrated for combination compared to monotherapy. However, overweight/obese individuals were less likely to achieve remission overall (non-significant). Regarding components of remission, tender joint count and ESR in estRA were higher in overweight/obese individuals at 6 months [β 1.05 (95%CI 0.05-2.06)] and 12 months [β 6.58 (95%CI 0.16-12.99)] respectively, compared to those of normal weight. Sensitivity analyses showed no difference in the above results. MTX-dose was available for 613 patients at sequential visits. Within this subgroup, overweight/obese patients with both eRA and estRA were exposed to higher doses of MTX (mono- and combination-therapy) at any time-point, compared to those of normal weight. eRA: overweight: β 5.33, 95%CI 3.10-7.56; obese: β 6.01, 95%CI 3.57-8.46. estRA: overweight: β 4.87, 95%CI 3.79-5.95; obese: β 2.69, 95%CI 1.56-3.83. An average weekly dose of 20mg was prescribed in overweight/obese patients, compared to 15mg in those of normal weight. Conclusion We observed that overweight/obese individuals require more intense csDMARD therapy to achieve the same treatment targets as those of normal weight. Awareness of this is particularly important given the increasing obesity prevalence in RA. Disclosures M. Dey None. S.S. Zhao None. E. Psarelli None. R.J. Moots None. R. Landewe Other; Member of METEOR board. N.J. Goodson None.

P07 Improving patient care in psoriatic arthritis through quality improvement and audit against the National Institute for Health and Care Excellence NG65 guidelines

Abstract Background NICE guidelines (NG65) for diagnosis and management of spondyloarthritis (SpA) in over 16s provide evidence-based recommendations for provision of care and services for patients, with an aim to improving quality of care. There often appears to be misdiagnosis/under diagnosis of psoriatic arthritis (PsA), as well as unmet needs of achieving treatment to target and low disease activity. Our objective was to audit our PsA service against the guidelines to benchmark current service provision compared to the National recommendations, highlighting potential key areas to improve quality of SpA and PsA patient care and enable service development including our new electronic patient pathway. Methods The NICE baseline assessment tool was used to audit 100 patients diagnosed with PsA, attending the outpatient rheumatology clinic between 2017-2019. The mean age was 54, with a 3:2 female to male ratio. 30% of patients included were on a biologic disease modifying anti-rheumatic drug (bDMARD). Data was collected from clinic letters/medical/physiotherapy records. Data was collated to identify areas of compliance of our service against the guidelines, with the key outcomes scrutinised being assessment and diagnosis, imaging, information and support, pharmacological management and long-term condition management. Results 78% of patients with PsA had documentation of meeting the CASPAR or peripheral ASAS Criteria. 83% of patients who had symptomatic hands/feet obtained X-rays, and 82% had imaging of other peripheral or axial sites. 58% of patients with PsA had documented evidence of having received information on PsA. Out of 100% of patients that were started on a conventional synthetic DMARD (csDMARD), 83% that were on monotherapy were escalated to either an additional csDMARD or a bDMARD. Largely by month 3 the csDMARD was switched or the patient started combination therapy, in comparison to those that started a bDMARD which occurred largely around month 6. 100% of patients had access to flare management advice and flare clinic, but only 30% had documented discussions about cardiovascular (CV) and skin cancer risks on anti-TNF therapy. Subsequent action plans for service improvement included: a best practice pathway developed on the electronic patient records (EPR), including the CASPAR and ASAS criteria, the Group for Research and Assessment of Psoriasis (GRAPPA) 6 domains of PsA, CV and skin cancer risk. All patients are seen in the Nurse/therapist led education sessions for information on the disease. Conclusion Performing an audit of patients against the NG65 guidelines ensured that we were using real-world data to benchmark our service, enabling robust action plans to be developed to address low compliance areas. Consequently, the audit allowed us to justify changing and developing the service for improved patient care. Disclosures E.J. Papadopoulos: Other; Paid work with Novartis Pharmaceuticals. A. Chan: Member of speakers’ bureau; Novartis, Celgene, Janssen, Sanofi. Other; Advisory Board for: Novartis, Celgene, Lilly. K. Rigler: Other; aid work for Novartis Pharmaceuticals. A. Kachwaha: None. J. Gunn: None. N. Zabbey: None. E. Walsh: None.

P272 How well are conventional DMARDs tolerated in PsA: a real-world study

Abstract Background NICE guidelines recommend the first line use of DMARDs in psoriatic arthritis (PsA). However, studies show that many conventional treatments like methotrexate are poorly tolerated. There is hitherto no published real-world data addressing the tolerability of DMARDs in PsA. Our objective was therefore to assess the drug management in PsA with focus on tolerability and the reasons for therapy cessation. Methods We conducted a retrospective analysis of all PsA patients enrolled in electronic database up to April 2019 at our university teaching hospital. We had access to full patient records including details on co-morbidities, drugs and disease management. Results 335 patients were identified with a formal diagnosis of PsA. Mean age of the cohort was 46 years (13-81) and 58% were female. 9% of the individuals had diabetes and 18% had concurrent cardiovascular disease. 1/10th reported to be current smokers and 8% had a diagnosis of depression. 48% of the group had clinically active disease. Same percentage were taking a single DMARD. 10% had trialled 3 or more drugs. 62% of patients had discontinued one or more DMARDs prior. The mean duration before discontinuing a DMARD was 9.9 months. Methotrexate was the best tolerated and on average discontinued after 13.4 months (range: 4 days to 10.9 years). Sulfasalazine and hydroxychloroquine were discontinued after an average of 8.4 (11 days to 4.27 years) and 12.5 months (1.3 months to 2.88 years) respectively. Leflunomide was the least tolerated DMARD and stopped after an average of 5.5 months (7 days to 2.53 years). The main reason for stopping a medication was gastro-intestinal symptoms which accounted for 42% of all the reported side effects. This applied to both methotrexate (43%) and sulfasalazine (46%) discontinuation. The leading reasons for discontinuing hydroxychloroquine were jointly GI symptoms and other side effects at 43% each. Leflunomide was stopped in 50% of cases due to neurological symptoms. Conclusion To our knowledge, this is the first report confirming poor retention rate of oral DMARDs in a real world PsA cohort managed over 20 years. In the context of chronic disease, the median duration of treatment is short. Our analysis did not include patients who suffer from side effects but continue therapy thereby impacting treatment adherence and hence the true scale of the issue is likely higher. Though NICE guidelines stipulate the need of an adequate trial of minimum two DMARDs prior to therapy escalation, these drugs are not well tolerated and thus pose a challenge to clinicians. One potential solution is earlier adoption of biological therapies, which are increasingly cost effective and have been shown to be better tolerated. Disclosures I. Jawad None. M.K. Nisar None.

P32 Should we continue to test for latent tuberculosis infection in patients treated with biologics?

Abstract Background Timely diagnosis of tuberculosis (TB) infection is important in patients receiving biologics. Current BSR guidelines on biologic safety in inflammatory arthritis (2018) advise to screen all patients for TB before starting treatment. Due to limitations of tuberculin skin test (TST), IFN-γ release assay (IGRA) is frequently used in addition to clinical examination, risk assessment and chest x-ray (CXR). There are no clear guidelines whether IGRA should be part of follow up assessments. The Royal College of Nursing suggest patients on biologics should have repeat CXR in 3 months after starting biologics and then annually. The American College of Rheumatology suggest an annual TST or IGRA for high-risk individuals receiving biologics. Centers for disease control and prevention guidelines allows to use TST and IGRA for surveillance in selected population. Methods We present two cases in which patients developed TB after starting biologics. Both patients had negative IGRA, normal CXR and low risk of developing TB on prebiologic screening. Results First patient was a 64-year-old female with rheumatoid arthritis diagnosed in 2001. She failed multiple conventional DMARDs and was started on Certolizumab in 2014. Prebiologic screen showed a negative IGRA (T Spot) and CXR was clear. She was a smoker and her mother had pulmonary TB when she was a child. After 4 years she presented with weight loss and cough. CXR showed 1.4 cm round opacity in right upper lobe. She underwent surgical resection and histology showed acid fast bacilli on ZN stain with superimposed aspergilloma. She was started on quadruple therapy and we switched Certolizumab to Etanercept due to its shorter half-life. Second patient was a 27-year-old man with ankylosing spondylitis diagnosed in 2015. He was a smoker and had no past medical history. He was started on Adalimumab in 2016. T Spot was negative and CXR was clear. There were no risk factors for TB. Two years later he presented with multiple tender subcutaneous nodules over thighs and lower abdomen. Skin biopsy after dermatology assessment showed superficial and deep perivascular inflammation with lymphocytes and small number of eosinophils. Differential were granulomatous infection or panniculitis due to injection site reaction. TB cultures came back negative but repeat T Spot was positive. He was treated as latent TB infection for 3 months and Adalimumab was restarted without any problems. Conclusion Current BSR guidelines advise to monitor patient clinically for any signs of TB while receiving biologics. We suggest that there is a need to review whether TST or IGRA should be done annually on high risk patients along with CXR. Disclosures A.A. Sidhu None. A. Nandagudi None.

O10 Combining clinical and ultrasound assessment to taper biologic therapies in patients with RA in routine clinical practice

Abstract Background There is growing evidence for tapering biologic therapies in patients with rheumatoid arthritis in sustained clinical remission to avoid overtreatment and minimise side-effects. Ultrasound assessment for subclinical synovitis adds to clinical assessment of patients with rheumatoid arthritis suitable for tapering biologic therapies. Our primary objective was to combine clinical and ultrasound assessment to select patients with rheumatoid arthritis for tapering biologic therapies in routine clinical practice. The secondary objectives were to identify predictors for successful tapering and assess the cost savings to the local health economy by optimising the use of high cost drugs. Methods All patients with rheumatoid arthritis on a biologic therapy for 2 years and in sustained clinical remission (DAS28≤2.6) over the previous year were seen in the remission clinic. They had an Ultrasound scan of the small joints of the hands, wrists and other symptomatic joints. Patients with no activity on Power Doppler were advised to lengthen the interval of their biologic therapy gradually and were followed once every 3 months. Patients were not on oral steroids but continued conventional DMARDs. Patients had a dedicated helpline if they had a flare. Results Ninety-three of the 120 patients with rheumatoid arthritis on biologic therapy seen in the biologic remission clinic between January and October 2019 were eligible and all but one agreed to taper. They were 70% female with a mean age of 62.8 years and mean duration of disease 14.6 years. Their mean duration of biologic therapy was 6.3 years; mean baseline DAS28 was 6.3 pre-biologic therapy and 1.7 before tapering. Fifty-seven of the patients were on a TNF inhibitor and 35 were on other biologic therapies. Forty of the ninety-two patients were co-prescribed DMARDs. Screening failure was due to clinical activity in 13 patients, Ultrasound Power Doppler activity in 23 patients, interstitial lung disease in 2 patients and shoulder surgery in one. Only two of the 40 patients who had completed 6 months had a flare and reverted to the baseline frequency. Of the remaining 52 patients, 22 patients had completed 3 months at the tapered dose and 3 patients who were in the initial 3 months had a flare and reverted to the baseline frequency. Initial drug-cost savings at 6 months was approximately £45,000. Conclusion Tapering of biologic therapies in patients with rheumatoid arthritis is feasible in routine clinical practice. Ultrasound is helpful to stratify patients for biologic tapering and has enabled a higher proportion of patients to remain in remission after tapering. Disclosures H. Pillai: None. N. Nolkha: None. A. Yau: None. S. Matthews: None. A. Hall: None. G. Hirsch: None. S. Venkatachalam: None.

P29 Use of novel biologic therapies for arthropathy affecting common variable immunodeficiency patients

Abstract Background CVID is the most common adult immunodeficiency with an incidence of 1:25000. It is characterised by hypogammaglobulinaemia and recurrent bacterial infections. Patients also develop granulomatous interstitial lung disease and are at increased risk of lymphoma. Autoimmune disease, most commonly AIHA, ITP and thyroiditis, occurs at a rate of 25%. Previous studies suggested that 3% of patients have inflammatory arthritis, but from our experience a higher proportion complain of chronic arthralgias. Treating arthropathy in CVID is challenging; examination and inflammatory markers may be normal and there is concern about the risk of infections if using methotrexate or biologics. Methods We present a series of 7 patients with arthropathy in CVID. We chose DMARDs based on the individual case, tailor-made to the patients clinical and immunologic status. Results Patients had longstanding symptoms, with a median duration of 11 years. All patients had disabling joint pain, in three it was the most prominent symptom of their illness. All patients had pain/swelling in a typical symmetrical small joint polyarthritis distribution. Fatigue was also prominent. On examination three patients had clear evidence of synovitis, one had tenderness but no swelling, and three had no evidence of synovitis; there was no deformity. No patient had positive autoantibodies. Three had chronically raised CRP/ESR, one had raised inflammatory markers during flares, but the other three had normal markers. Prednisolone (10-15 mg) controlled arthritic symptoms. There was little response to conventional DMARDS or rituximab. Two patients treated with abatacept showed improvement in symptoms, but one died from PJP pneumonia. Two patients treated with baricitinib showed improvement in symptoms but one relapsed after 5 months (Table 1). Conclusion Arthopathy is a common, and probably under-diagnosed, feature of CVID. It is difficult to treat, with a poor response seen to most DMARDs. We have seen promising results with Baricitinib and propose using it first line in patients with disabling rheumatic symptoms. There may be a role for abatacept in co-existent severe joint and lung disease. A striking proportion, 4/7 (versus 10% in general CVID population), of patients had a causal genetic mutation identified. Arthropathy may, therefore, push immunologists towards genetic testing. Disclosures R. Henneberry None. S. Burns None. R. Stratton None. D.M. Lowe None.

The safety of baricitinib in patients with rheumatoid arthritis

ABSTRACTIntroduction: Despite improvement in disease outcomes and prognosis, a substantial number of patients with rheumatoid arthritis (RA) still require a novel agent for effective treatment. Baricitinib is a targeted synthetic disease-modifying antirheumatic drug (tsDMARDs) that selectively inhibits Janus kinase (JAK1/JAK2), an important enzyme in the pathogenesis of RA.Areas covered: This paper aimed to evaluate the pharmacodynamics and pharmacokinetics of baricitinib while reviewing its safety and efficacy in the treatment of RA.Expert opinion: Randomized controlled trials of baricitinib showed its efficacy and safety in patients with active RA who were methotrexate (MTX)-naïve or were not adequately responsive to MTX, conventional synthetic DMARDs, or tumor necrosis factor inhibitors. Baricitinib may be suitable in patients who prefer oral therapy and do not have a history of severe renal impairment, recent history of malignancy, or risk factors for adverse events (AEs) such as venous thromboembolism, opportunistic infection, and diverticulitis. Dose adjustment of baricitinib, based on the assessment of patient conditions including their renal function and disease activity, is an important strategy for successful and safe treatment. However, long-term post-marketing surveillance studies with a larger sample size are required to evaluate the overall safety and AEs with low incidence rates in clinical settings.

Biologicals and small molecules for rheumatoid arthritis

In recent years tremendous progress has been made in the therapeutic management of rheumatoid arthritis. Rheumatologists now have alarge armamentarium of highly efficient drugs with different mechanisms of action at their disposal. These new drugs consist of biologicals (biological disease-modifying antirheumatic drugs, bDMARDs) as well as targeted synthetic DMARDs (tsDMARD). A common feature of these new drugs for treatment of rheumatoid arthritis is that the molecular target of the drug is known, which is not the case for conventional DMARDs. With the help of the new drugs, the therapeutic goal of inducing remission in patients with rheumatoid arthritis has become reality for many patients. Nevertheless, there is still asignificant proportion of patients who do not adequately respond to all available drugs, leaving room for still further improvement. This review gives ashort overview on the currently available and effective substances for the treatment of rheumatoid arthritis.

Primary Sjögren's Syndrome - News on Diagnostics and Therapy

Primary Sjögren's Syndrome - News on Diagnostics and Therapy Abstract. Primary Sjögren's syndrome is an autoimmune disease that affects primarily the exocrine glands and is mainly characterized by sicca symptoms of the eyes and mouth, but also nose, throat, vagina and skin can be affected. Fatigue and pain are also very characteristic. Systemic manifestations can occur, e.g. in joints, muscles, lungs, kidneys, skin or the nervous system. A feared complication is the development of a lymphoma, the risk being especially high in case of positive anti-SSA-(Ro) antibodies, but also in case of a high ESSDAI score, hypocomplementemia, cytopenia or evidence of ectopic germinal centers in salivary gland biopsies. Diagnosis is principally made by verification of sicca symptoms (e.g. Schirmer's test) and detection of typical antibodies or a typical gland biopsy. Sicca symptoms are primarily treated symptomatically (e.g. artificial tears or saliva). In case of systemic manifestations glucocorticoids, conventional DMARDs or biologics (mostly rituximab) are treatment options. In severe cases, intravenous immunoglobulins or plasma exchange may be required.