Implementing Treat to Target (TTT) for Rheumatoid Arthritis (RA) During COVID: Results of a Virtual Learning Collaborative (LC) Program

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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POS0495 LARGE JOINT DISEASE IN RHEUMATOID ARTHRITIS AND THE ROLE OF RHEUMATOID FACTOR. RESULTS FROM THE EARLY RHEUMATOID ARTHRITIS STUDY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3626 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 480-480

Author(s):

S. S. Zhao ◽

E. Nikiphorou ◽

A. Young ◽

P. Kiely

Keyword(s):

Rheumatoid Arthritis ◽

Rheumatoid Factor ◽

Treatment Strategies ◽

Treat To Target ◽

Joint Involvement ◽

Aggressive Treatment ◽

Joint Surgery ◽

Large Joint ◽

Significant Difference ◽

Over Time

Background:Rheumatoid arthritis (RA) is classically described as a symmetric small joint polyarthritis with additional involvement of large joints. There is a paucity of information concerning the time course of damage in large joints, such as shoulder, elbow, hip, knee and ankle, from early to established RA, or of the influence of Rheumatoid Factor (RF) status. There is a historic perception that patients who do not have RF follow a milder less destructive course, which might promote less aggressive treatment strategies in RF-negative patients. The historic nature of the Ealy Rheumatoid Arthritis Study (ERAS) provides a unique opportunity to study RA in the context of less aggressive treatment strategies.Objectives:To examine the progression of large joint involvement from early to established RA in terms of range of movement (ROM) and time to joint surgery, according to the presence of RF.Methods:ERAS was a multi-centre inception cohort of newly diagnosed RA patients (<2 years disease duration, csDMARD naive), recruited from 1985-2001 with yearly follow-up for up to 25 (median 10) years. First line treatment was csDMARD monotherapy with/without steroids, favouring sulphasalazine for the majority. Outcome data was recorded at baseline, at 12 months and then once yearly. Patients were deemed RF negative if all repeated assessments were negative. ROM of individual shoulder, elbow, wrist, hip, knee, ankle and hindfeet joints was collected at 3, 5, 9 and 12-15 years. The rate of progression from normal to any loss of ROM, from years 3 to 14 was modelled using GEE, adjusting for confounders. Radiographs of wrists taken at years 0, 1, 2, 3, 5, 7, 9 were scored according to the Larsen method. Change in the Larsen wrist damage score was modelled using GEE as a continuous variable, while the erosion score was dichotomised into present/absent. Surgical procedure data were obtained by linking to Hospital Episodes Statistics and the National Joint Registry. Time to joint surgery was analysed using multivariable Cox models.Results:A total of 1458 patients from the ERAS cohort were included (66% female, mean age 55 years) and 74% were RF-positive. The prevalence of any loss of ROM, from year 3 through to 14 was highest in the wrist followed by ankle, knee, elbow and hip. The proportion of patients at year 9 with greater than 25% loss of ROM was: wrist 30%, ankle 12%, elbow 7%, knee 7% and hip 5%. Odds of loss of ROM increased over time in all joint regions, at around 7 to 13% per year from year 3 to 14. There was no significant difference between RF-positive and RF-negative patients (see Figure 1). Larsen erosion and damage scores at the wrists progressed in all patients; annual odds of developing any erosions were higher in RF-positives OR 1.28 (95%CI 1.24-1.32) than RF-negatives OR 1.17 (95%CI 1.09-1.26), p 0.013. Time to surgery was similar according to RF-status for the wrist and ankle, but RF-positive cases had a lower hazard of surgery at the elbow (HR 0.37, 0.15-0.90), hip (HR 0.69, 0.48-0.99) and after 10 years at the knee (HR 0.41, 0.25-0.68). Adjustment of the models for Lawrence assessed osteoarthritis of hand and feet radiographs did not influence these results.Figure 1.Odds of progression to any loss of ROM (from no loss of ROM) per year in the overall population and stratified by RF status.Conclusion:Large joints become progressively involved in RA, most frequently affecting the wrist followed by ankle, which is overlooked in some composite disease activity indices. We confirm a higher burden of erosions and damage at the wrists in RF-positive patients, but have not found RF-negative patients to have a better prognosis over time with respect to involvement of other large joints. In contrast RF-negative patients had more joint surgery at the elbow, hip, and knee after 10 years. There is no justification to adopt a less aggressive treatment strategy for RF-negative RA. High vigilance and treat-to-target approaches should be followed irrespective of RF status.Disclosure of Interests:None declared

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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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