THU0172 Improvement of disease activity in a 5-year cohort of rheumatoid arthritis patients treated under treat to target recommendations and a multispeciality care model receiving conventional dmard therapy

Background:The principles of treat to target (T2T) include defining an appropriate treatment target, assessed at pre-defined intervals, with a commitment to changing therapeutic approach if the target is not met (1). T2T is recommended as a key strategy for the treatment of rheumatoid arthritis (RA).Objectives:To explore attitudes towards T2T, its implementation and stated treatment goals among physicians and their patients with RA.Methods:The Adelphi RA Disease Specific Programme™ was a large, quantitative, point-in-time survey conducted amongst rheumatologists (n=296) and their consulting patients with RA (n=3042) in Europe (France, Germany, Italy, Spain, UK) between Q4 2019–Q3 2020. Physicians were recruited via publicly available lists, completing an online survey and medical record extraction for their next 10–12 consecutive patients. The same patients were invited to voluntarily complete a self-report questionnaire (n=1098, 36% response), collecting data on attitudes towards T2T and treatment goals.Results:Physicians reported that 76% of patients were in remission (DAS28: <2.6) or had low disease activity (DAS28: 2.6 – 3.2), and 24% had moderate-high disease activity (DAS28: >3.2). Patient mean age was 53.0 years (SD 14.0), mean time since diagnosis was 7.2 years (SD 7.2). The proportion of patients currently receiving an advanced therapy (AT; defined as biologic or targeted synthetic DMARD) was 68%, of whom 70% were on a first line AT. No difference was observed between disease activity groups.In the physician survey, 86% of physicians stated they followed T2T principals in at least some of their RA patients, and would utilize a T2T approach in RA patients with moderate-high disease activity (61%), the most uncontrolled patients (37%) and those who do not respond well to initial therapy (34%). In this sample of real-world RA patients, 66% were reported by physicians to be on a T2T plan at the time of data collection. The most common physician-reported targets were remission (DAS28: <2.6) (75%), improvement of quality of life (QoL) (41%) and reduction of pain (31%), with 85% of physicians perceiving these treatment goals were fully or partially met. The most stated reasons for not implementing T2T was physician preference not to adjust current treatment (34%), patient preference not to adjust current treatment (23%), and there are no achievable goals for this patient (16%).Overall, 29% of patients reported they were involved in setting their T2T goals, while 34% stated their T2T goals were set by their physicians only, and 29% perceived no T2T goal had been set (n=620). The most common overall T2T goals from the patient perspective were remission (61%), controlling symptoms (41%), and reducing impact on QoL (34%). Of those patients who acknowledged a T2T goal had been set (n=407), 77% reported their T2T goal was fully or partially achieved.Of 719 patients who had moderate-high disease activity, 57% were on a T2T plan, with 46% of physicians perceiving these treatment goals were fully or partially met. The most common physician-stated reason for not implementing T2T was a lack of achievable targets (29%).Conclusion:Rheumatologists in this study reported a strong belief in T2T. The most common physician-set T2T goals were remission, improvement of QoL and reduction of pain, corresponding with T2T goals as reported by patients. However, a third of patients in this cohort were not aware of a defined T2T objective in their management, which may be a result of a perceived lack of achievable goals by physicians. It may be desirable to promote more patient involvement in defining achievable targets amongst those with moderate-high disease activity who despite best efforts may not reach a clinical state of remission. Further research is needed to identify and understand goals important to RA patients.References:[1]van Vollenhoven R. Treat-to-target in rheumatoid arthritis - are we there yet? Nat Rev Rheumatol. 2019;15(3):180-6.Acknowledgements:This study was funded by Galapagos NV, Belgium.Medical writing support was provided by Gary Sidgwick, PhD (Adelphi Real World, Bollington, UK) and editorial support was provided by Debbie Sherwood, BSc, CMPP (Aspire Scientific, Bollington, UK), both funded by Galapagos NV.Disclosure of Interests:Bruno Fautrel Consultant of: AbbVie, Amgen, Biogen, BMS, Celgene, Celltrion, Fresenius Kabi, Gilead, Janssen, Lilly, Medac, MSD, Mylan, NORDIC Pharma, Novartis, Pfizer, Roche, Sandoz, Sanofi-Genzyme, SOBI, UCB, Grant/research support from: AbbVie, Lilly, MSD, Pfizer, Roberto Caporali Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Celltrion, Galapagos, Gilead, Lilly, Pfizer, Roche, UCB, Sanofi, Fresenius Kabi, Samsung Bioepis, MSD, Consultant of: Galapagos, Gilead, Lilly, Janssen, MSD, Elizabeth Holdsworth Employee of: Adelphi Real World, Bethany Donaghy Employee of: Adelphi Real World, Mona Khalid Shareholder of: Galapagos, Employee of: Galapagos, Mark Moore Shareholder of: Gilead Sciences, Speakers bureau: Gilead Sciences (only as employee), Paid instructor for: Gilead Sciences (only as employee), Consultant of: Gilead Sciences (only as employee), Grant/research support from: Gilead Sciences (only as employee), Employee of: Gilead Sciences, and previously Sanofi and AstraZeneca, Katrien Van Beneden Shareholder of: Galapagos, Employee of: Galapagos, Yves Piette Consultant of: AbbVie, Amgen, Galapagos, Grünenthal and Sandoz, Grant/research support from: Amgen, Mylan and UCB, Susana Romero-Yuste Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Grunenthal, Kern Pharma, Lilly, Roche, Sandoz, Sanofi, UCB, Janssen, Consultant of: AbbVie, Biogen, Fresenius, Galapagos, Gebro, Janssen, Lilly, Grant/research support from: Bristol Myers Squibb, MSD, Novartis, Pfizer, Jasper Broen Shareholder of: Pharming Group, Consultant of: Galapagos, Gilead, Novartis, Peter C. Taylor Consultant of: AbbVie, Biogen, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, Pfizer, Roche, Sanofi, Nordic Pharma, Fresenius, UCB, Grant/research support from: Celgene, Galapagos, Gilead, Lilly

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POS0492 A MOLECULAR SIGNATURE RESPONSE CLASSIFIER PREDICTS THE LIKELIHOOD OF EULAR NON-RESPONSE TO TNF INHIBITOR THERAPIES IN RA: RESULTS FROM A RETROSPECTIVE COHORT ANALYSIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3396 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 478.2-479

Author(s):

L. Zhang ◽

C. van der Tog ◽

A. den Broeder ◽

T. Mellors ◽

E. Connolly-Strong ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Predictive Value ◽

Molecular Signature ◽

Response Criteria ◽

Treat To Target ◽

Inadequate Response ◽

Tnf Inhibitor ◽

Target Setting ◽

The Impact

Background:Following RA treatment recommendations, most people with rheumatoid arthritis (RA) begin targeted therapy with TNF inhibitors (TNFi), even though inadequate response to TNFi therapies is widespread. Treatment changes from one medication to the next are currently fueled by disease-activity measures and eventually result in disease control for most patients; however, this “trial-and-error” approach wastes precious time on ineffective treatments. A delay in reaching treat-to-target goals has a negative effect on patient burden and, possibly, disease progression.1 Useful predictors for TNFi response have been challenging to identify but a specific molecular signature response classifier (MSRC) test was shown to be predictive for inadequate response to TNFi therapies.2 The impact of such identification has the potential to result in improved patient outcomes, but further validation would be welcome, especially for response criteria other than ACR50, and in a stringent treat-to-target setting with lower baseline disease activity.Objectives:To validate the predictive value of the MSRC test in identifying those patients who do not meet EULAR good response criteria after 6 months of TNFi treatment.Methods:Data from a prospective cohort study conducted in the Sint Maartenskliniek (Nijmegen, the Netherlands) of RA patients who started adalimumab or etanercept TNFi as their first biologic were included.3 Baseline RNA samples and clinical assessments were used to identify patients who had a molecular signature1 of non-response to TNFi therapy. Outcomes were calculated at six months using DAS28-CRP-based EULAR good response, and high and low confidence responders and non-responders were identified using Monte Carlo simulation with 2,000 repeats and 70% precision cut off. Outcome measurements were blinded for test results. Treatment switch before 6 months was imputed as non-response. Odds ratios and area under the ROC curve (AUC) assessments were used to evaluate the ability of the MSRC test to predict inadequate response at 6 months against EULAR good response criteria.Results:A total of 68 out of 88 RA patients were identified to have a high-confidence response status and were included in analyses (Table 1). EULAR good response was observed in 45.5% (31/68) of patients. Patients were stratified according to detection of a molecular signature of non-response with an AUC of 0.61. The odds that a patient with the molecular signature of non-response at baseline failed to achieve a EULAR good response at 6 months was four times greater than that of a patient lacking the molecular signature (odds ratio 4.0, 95% confidence interval 1.2-13.3).Table 1.Patient demographicsCharacteristicRA patients (N = 68)Age, median (SD)57 (11)Female, n (%)43 (63.2)CCP positive, n (%)34 (50.0)RF positive, n (%)38 (55.9)Prescribed adalimumab at baseline, n (%)11 (16.2)Prescribed etanercept at baseline, n (%)57 (83.8)Conclusion:In this validation study, the molecular signature of non-response identified patients who did not fulfill the EULAR good response criteria to TNFi therapies. The patient selection process for this study had limitations; additional analysis in an alternative cohort would further verify the performance of the MSRC test. Nevertheless, the test, previously validated for ACR50, now has been validated using EULAR good response in a treat-to-target setting.References:[1]Schipper LG et al, Time to achieve remission determines time to be in remission. Arthritis Res Ther 201[2]Mellors T, et al. Clinical Validation of a Blood-Based Predictive Test for Stratification of Response to Tumor Necrosis Factor Inhibitor Therapies in Rheumatoid Arthritis Patients. Network and Systems Medicine 2020[3]Tweehuysen L et al. Predictive value of ex-vivo drug-inhibited cytokine production for clinical response to biologic DMARD therapy in rheumatoid arthritis. Clin Exp Rheumatol 2019Disclosure of Interests:Lixia Zhang Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Celeste van der Tog: None declared, Alfons den Broeder Consultant of: Abbvie, Amgen, Cellgene, Roche, Biogen, Lilly, Novartis, Celltrion Sanofi, Gilead., Grant/research support from: Abbvie, Amgen, Cellgene, Roche, Biogen, Lilly, Novartis, Celltrion Sanofi, Gilead., Ted Mellors Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Erin Connolly-Strong Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Johanna Withers Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Alex Jones Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Viatcheslav Akmaev Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation

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AB0302 USE OF TNF-INHIBITORS BEFORE, DURING AND THE FIRST YEAR AFTER PREGNANCY AMONG WOMEN WITH RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.3622 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1450.2-1450

Author(s):

H. Bjørngaard ◽

H. Koksvik ◽

B. Jakobsen ◽

M. Wallenius

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Post Partum ◽

Tnf Inhibitors ◽

Treat To Target ◽

Inflammatory Rheumatic Diseases ◽

Tnf Inhibitor ◽

Rheumatic Arthritis ◽

Quality Register ◽

In Pregnancy

Background:Treat to target is a goal, also in pregnant women with Rheumatoid arthritis (1). There is increasing evidence on safe use with TNF inhibitors during pregnancy. Adjusted use of TNF inhibitors preconception and throughout pregnancy may stabilize disease activity and prevent flares (2). Low disease activity is also beneficial for the fetus.Objectives:To study the use of TNF-inhibitors among women with Rheumatic arthritis during and after pregnancy.Methods:RevNatus is a Norwegian, nationwide quality register that monitors treatment of inflammatory rheumatic diseases before, during and after pregnancy. Data from RevNatus in the period October 2017 to October 2019 was used to map the use of all types of TNF inhibitors among 208 women with rheumatoid arthritis, diagnosed by the ACR/EULAR criteria. The use of medication was reported at the time of visit in outpatient clinic. The frequency of use of TNF inhibitors registered at seven timepoints from pre-pregnancy to twelve months after delivery.Results:The use of medication was reported at each visit for all the women with rheumatoid arthritis. Most of the women were not using TNF inhibitors before and beyond conception. Most of the women continuing TNF inhibitors beyond conception used certolizumab or etanercept. Adalimumab and infliximab were used in pregnancy (tabell 1).Tabell 1.certoliz-umabetane-rceptadalim-umabgolim-umabinflixi-mabNo TNF-inhibitorBefore pregnancyn=10521% (22)9% (10)3% (3)1% (1)66% (69)1.trimestern=8119% (15)10% (8)71% (58)2.trimestern=8810% (9)10% (9)80% (70)3.trimestern=9111% (10)5% (5)83% (76)6 weeks post partum n=9622% (21)13% (13)1% (1)1% (1)63% (60)6 months post partum n=8824% (21)18% (16)4% (4)1% (1)53% (46)12 months post partum n=8421% (18)17% (15)7% (6)2% (2)53% (43)Conclusion:Most of the women with rheumatic arthritis were not treated with TNF inhibitors before or in pregnancy. Women with rheumatic arthritis that continuing treatment with TNF inhibitors through pregnancy were using certilozumab and etanercept.References:[1]Gotestam Skorpen C, Hoeltzenbein M, Tincani A, Fischer-Betz R, Elefant E, Chambers C, et al. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. 2016;75(5):795-810.[2]van den Brandt S, Zbinden A, Baeten D, Villiger PM, Ostensen M, Forger F. Risk factors for flare and treatment of disease flares during pregnancy in rheumatoid arthritis and axial spondyloarthritis patients. Arthritis Res Ther. 2017;19(1):64.Disclosure of Interests:None declared

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POS0455 EFFECT OF ANTI-Ro/SSA ANTIBODIES FOR TREATMENT RESPONSE TO METHOTREXATE IN RHEUMATOID ARTHRITIS: A RETROSPECTIVE MULTICENTER OBSERVATIONAL STUDY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.1485 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 458.1-458

Author(s):

R. Yokochi ◽

H. Tamai ◽

T. Kido ◽

Y. Yagyu ◽

D. Waki ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Logistic Regression ◽

Regression Analysis ◽

Disease Activity ◽

Clinical Response ◽

Logistic Regression Analysis ◽

Age At Onset ◽

Treat To Target ◽

Low Disease Activity ◽

Target Strategy

Background:Several previous observational studies have suggested that patients with anti-Ro/SSA antibody-positive rheumatoid arthritis (RA) may respond poorly to treatment, including tumor necrosis factor inhibitors1. However, its influence on methotrexate (MTX) treatment, which is the anchor drug of treat-to-target strategy in RA treatment, remains unclear.Objectives:We compared the clinical response to MTX in both anti-Ro/SSA antibody-positive and -negative patients with MTX-naiive RA and investigated the reasons for the difference in response.Methods:We recruited 210 consecutive patients with RA who were newly started on MTX in this retrospective cohort study. The effect of the presence of anti-Ro/SSA antibodies on achieving low disease activity (LDA) of DAS28-CRP at six months after initiating MTX was investigated by using logistic regression analysis. CDAI, SDAI, concomitant using DMARDs and painkillers, patient’s and evaluator’s VAS, tender joint counts, and swollen joint counts at six months were also compared between the anti-Ro/SSA-positive patients and -negative patients. Missing data were imputed by using multiple imputations before multivariate analysis.Results:32 anti-Ro/SSA antibody-positive patients and 178 anti-Ro/SSA antibody-negative patients were included. The rate of achieving DAS28-LDA at six months was significantly lower in the anti-Ro/SSA antibody-positive patients than those in the anti-Ro/SSA antibody-negative patients (56.2% versus 75.8%, P=0.03). in the logistic regression analysis, the presence of anti-Ro/SSA antibodies was an independent negative predictor for achieving DAS-28-LDA at six months (OR:0.431, 95%CI: 0.190-0.978, P=0.044) (Table1). Anti-Ro/SSA antibody-positive patients had significantly higher patient’s VAS at six months (median [IQR]: 22 [15-41] vs 19 [5-30], P=0.038), and prescribed NSAIDs (37.5% vs 18.0%, P=0.018). CDAI and SDAI after six months were not significantly different between the group.Conclusion:The presence of anti-Ro/SSA antibodies might be one of the predictive factors for the insufficient response to treat to target strategy in RA treatment. Residual pain was suspected as one of the mechanisms contributing to the lesser clinical response of MTX in anti-Ro antibody-positive RA.References:[1]Ran Matsudaira wt al. J Rheumatol 2011;38(11):2346-54Table 1.Logistic regression analysis for the rate of achieving DAS28 low disease activity at six months.Risk factor Odds ratio95%CIP valueAge at onset0.9930.968-1.0180.586Sex (woman)0.6430.300-1.3840.258RF-positive1.9620.853-4.5110.112ACPA-positive0.5520.225-1.3510.192Anti-Ro/SSA antibody-positive0.4310.190-0.9780.044Disclosure of Interests:None declared

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Monitoring of rheumatoid arthritis disease activity in individual patients: still a hurdle when implementing the treat-to-target principle in daily clinical practice

Rheumatology ◽

10.1093/rheumatology/keu334 ◽

2014 ◽

Vol 54 (6) ◽

pp. 959-961 ◽

Cited By ~ 9

Author(s):

J. W. G. Jacobs ◽

D. F. Ten Cate ◽

J. M. van Laar

Keyword(s):

Rheumatoid Arthritis ◽

Clinical Practice ◽

Disease Activity ◽

Daily Clinical Practice ◽

Treat To Target ◽

Rheumatoid Arthritis Disease Activity ◽

Rheumatoid Arthritis Disease

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SAT0089 Initiating tofacitinib in a treat to target strategy for rheumatoid arthritis leads to blunted multi-biomarker disease activity scores as compared to anti-tumour necrosis factor agents

10.1136/annrheumdis-2018-eular.3995 ◽

2018 ◽

Author(s):

C. Wiesenhutter

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Tumour Necrosis Factor ◽

Tumour Necrosis ◽

Treat To Target ◽

Target Strategy ◽

Necrosis Factor

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Do Poor Prognostic Factors in Rheumatoid Arthritis Affect Treatment Choices and Outcomes? Analysis of a US Rheumatoid Arthritis Registry

The Journal of Rheumatology ◽

10.3899/jrheum.171050 ◽

2018 ◽

Vol 45 (10) ◽

pp. 1353-1360 ◽

Cited By ~ 3

Author(s):

Evo Alemao ◽

Heather J. Litman ◽

Sean E. Connolly ◽

Sheila Kelly ◽

Winnie Hua ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Prognostic Factors ◽

Disease Activity ◽

Clinical Outcomes ◽

Activity Index ◽

Functional Limitation ◽

Disease Activity Index ◽

Treat To Target ◽

Work Status ◽

Logistic Regression Models

Objective.To characterize patients with rheumatoid arthritis (RA) by number of poor prognostic factors (PPF: functional limitation, extraarticular disease, seropositivity, erosions) and evaluate treatment acceleration, clinical outcomes, and work status over 12 months by number of PPF.Methods.Using the Corrona RA registry (January 2005–December 2015), biologic-naive patients with diagnosed RA having 12-month (± 3 mos) followup were identified and categorized by PPF (0–1, 2, ≥ 3). Changes in medication, Clinical Disease Activity Index (CDAI), and work status (baseline–12 mos) were evaluated using linear and logistic regression models.Results.There were 3458 patients who met the selection criteria: 1489 (43.1%), 1214 (35.1%), and 755 (21.8%) had 0–1, 2, or ≥ 3 PPF, respectively. At baseline, patients with ≥ 3 PPF were older, and had longer RA duration and higher CDAI versus those with 0–1 PPF. In 0–1, 2, and ≥ 3 PPF groups, respectively, 20.9%, 23.2%, and 26.5% of patients received ≥ 1 biologic (p = 0.011). Biologic/targeted synthetic disease-modifying antirheumatic drug (tsDMARD) use was similar in patients with/without PPF (p = 0.57). After adjusting for baseline CDAI, mean (standard error) change in CDAI was −4.95 (0.24), −4.53 (0.27), and −2.52 (0.34) for 0–1, 2, and ≥ 3 PPF groups, respectively. More patients were working at baseline but not at 12-month followup in 2 (13.9%) and ≥ 3 (12.5%) versus 0–1 (7.3%) PPF group.Conclusion.Despite high disease activity and worse clinical outcomes, number of PPF did not significantly predict biologic/tsDMARD use. This may warrant reconsideration of the importance of PPF in treat-to-target approaches.

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