Sustained Low Disease Activity Research Articles

Patient-reported outcomes and radiographic progression in patients with rheumatoid arthritis in sustained remission versus low disease activity

ObjectiveTo compare clinical and patient-reported outcomes (PROs) over 5 years between patients with rheumatoid arthritis (RA) in sustained remission (sREM), sustained low disease activity (sLDA) or active disease (AD) in...

Moderate and high disease activity levels increase the risk of subclinical atherosclerosis progression in early rheumatoid arthritis: a 5-year prospective study

ObjectivesTo elucidate the association between different disease activity levels over time on long-term vascular outcomes in patients with early rheumatoid arthritis (ERA).MethodsThis was a 5-year prospective study. Patients with consecutive...

Ten-year radiographic and functional outcomes in rheumatoid arthritis patients in remission compared to patients in low disease activity

BackgroundTo compare the 10-year structural and functional prognosis between patients in sustained remission versus patients in sustained low disease activity (LDA) in early rheumatoid arthritis (RA).MethodsWe included 256 patients from the ESPOIR cohort who fulfilled the 2010 ACR/EULAR criteria for RA and who were in sustained remission using the Simple Disease Activity Index (SDAI) score (n = 48), in sustained LDA (n = 139) or in sustained moderate to high disease activity (MDA or HDA, n = 69) over 10 years. The mTSSs progression over 10 years and the 10-year HAQ-DI scores were compared between the 3 groups. A longitudinal latent process mixed model was used to assess the independent effect of SDAI status over time on 10-year mTSS progression and HAQ-DI at 10 years.ResultsPatients in sustained remission group were younger, had lower baseline HAQ-DI and mTSS scores and were less exposed to glucocorticoids, methotrexate or biologic disease-modifying anti-rheumatic drugs over 10 years. Patients in sustained remission had lower 10-year structural progression (variation of mTSS in the remission group: 4.06 (± 4.75) versus 14.59 (± 19.76) in the LDA group and 21.04 (± 24.08), p < 0.001 in the MDA or HDA groups) and lower 10-year HAQ-DI scores (10-year HAQ-DI in the remission group: 0.14 (± 0.33) versus 0.53 (± 0.49) in the LDA group and 1.20 (± 0.62) in the MDA or HDA groups, p < 0.001). The incidence of serious adverse events over 10 years was low, about 3.34/100 patient years, without any difference between the three groups.ConclusionRA patients in sustained SDAI remission have better long-term structural and functional outcomes in comparison to patients in sustained LDA.

A real-world 2-year prospective study of medication tapering in patients with well-controlled rheumatoid arthritis within the rheumatoid arthritis medication tapering (RHEUMTAP) cohort.

This study had two aims: (i) to investigate outcomes of medication tapering in stable RA patients on biologic or targeted synthetic disease-modifying anti-rheumatic drugs (bDMARDs/tsDMARDs) and conventional synthetic DMARDs (csDMARDs) in a real-world prospective cohort; and (ii) to evaluate possible predictors of flare with medication taper. A prospective cohort of patients with RA in sustained remission or low disease activity while on stable bDMARD/tsDMARDs +/- csDMARDs for at least 6 months underwent medication tapering/stopping and was tracked for 2 years. Patients were evaluated for flares in four groups: no taper, only bDMARD/tsDMARD taper, only csDMARD taper and both csDMARD and bDMARD/tsDMARD taper. The RHEUMTAP cohort included 131 patients that met eligibility criteria, of which 52 patients underwent a medication taper. Flare was experienced by 15 patients in the taper and twoin the no-taper groups. Patients undergoing any taper/stop overall were 10 times more likely to experience a flare compared with those not tapered (HR 10.43, 95% CI 2.98-36.53, P = 0.0002). The group tapering bDMARD/tsDMARD had 31 times higher risk of flare (HR 31.43, 95% CI 6.35-155.55, P<0.0001) than the no-taper group. Patients tapering both csDMARDs and bDMARD/tsDMARDs had 18 times higher risk of flare than the no-taper group (HR 18.45, 95% CI 2.55-133.37, P = 0.0039). The only csDMARD taper group had a 91% lower risk of flare than the bDMARD/tsDMARD taper group (HR 0.09, 95% CI 0.01-0.69, P = 0.0213). In our real-world prospective RHEUMTAP cohort study on the outcomes of different medication tapering groups in well-controlled RA, patients who tapered or stopped bDMARDs/tsDMARDs with or without background therapy were more likely to experience a flare than patients that did not taper any medications and those that tapered only csDMARDs.

Secukinumab improves physical function and quality of life and inhibits structural damage in patients with PsA with sustained remission or low disease activity: results from the 2-year phase 3 FUTURE 5 study

ObjectiveTo investigate the impact of sustained low disease activity (LDA)/remission (REM) on physical function, quality of life (QoL) and structural outcomes in secukinumab-treated psoriatic arthritis (PsA) patients from the FUTURE...

Sustained remission following the discontinuation of tofacitinib in patients with rheumatoid arthritis (XANADU study): an open-label randomised study

ObjectiveTo investigate sustained remission following the discontinuation of tofacitinib in patients with rheumatoid arthritis.MethodsPatients who had an inadequate response to methotrexate (MTX) with or without biological disease-modifying antirheumatic drugs were...

Continuation, reduction, or withdrawal of tofacitinib in patients with rheumatoid arthritis achieving sustained disease control: a multicenter, open-label, randomized controlled trial.

Rheumatoid arthritis (RA), a chronic systemic autoimmune disease, is characterized by synovitis and progressive damage to the bone and cartilage of the joints, leading to disability and reduced quality of life. This study was a randomized clinical trial comparing the outcomes between withdrawal and dose reduction of tofacitinib in patients with RA who achieved sustained disease control. The study was designed as a multicenter, open-label, randomized controlled trial. Eligible patients who were taking tofacitinib (5 mg twice daily) and had achieved sustained RA remission or low disease activity (disease activity score in 28 joints [DAS28] ≤3.2) for at least 3 months were enrolled at six centers in Shanghai, China. Patients were randomly assigned (1:1:1) to one of three treatment groups: continuation of tofacitinib (5 mg twice daily); reduction in tofacitinib dose (5 mg daily); and withdrawal of tofacitinib. Efficacy and safety were assessed up to 6 months. Overall, 122 eligible patients were enrolled, with 41 in the continuation group, 42 in the dose-reduction group, and 39 in the withdrawal group. After 6 months, the percentage of patients with a DAS28-erythrocyte sedimentation rate (ESR) of <3.2 was significantly lower in the withdrawal group than that in the reduction and continuation groups (20.5%, 64.3%, and 95.1%, respectively; P < 0.0001 for both comparisons). The average flare-free time was 5.8 months for the continuation group, 4.7 months for the dose reduction group, and 2.4 months for the withdrawal group. Withdrawal of tofacitinib in patients with RA with stable disease control resulted in a rapid and significant loss of efficacy, while standard or reduced doses of tofacitinib maintained a favorable state. Chictr.org, ChiCTR2000039799.

Canadian Rheumatology Association Living Guidelines for the Pharmacological Management of Rheumatoid Arthritis With Disease-Modifying Antirheumatic Drugs.

To provide the initial installment of a living guideline that will provide up-to-date guidance on the pharmacological management of patients with rheumatoid arthritis (RA) in Canada. The Canadian Rheumatology Association (CRA) formed a multidisciplinary panel composed of rheumatologists, researchers, methodologists, and patients. In this first installment of our living guideline, the panel developed a recommendation for the tapering of biologic and targeted synthetic disease-modifying antirheumatic drug (b/ts DMARD) therapy in patients in sustained remission using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach, including a health equity framework developed for the Canadian RA population. The recommendation was adapted from a living guideline of the Australia &amp; New Zealand Musculoskeletal Clinical Trials Network. In people with RA who are in sustained low disease activity or remission for at least 6 months, we suggest offering stepwise reduction in the dose of b/tsDMARD without discontinuation, in the context of a shared decision, provided patients are able to rapidly access rheumatology care and reestablish their medications if needed. In patients where rapid access to care or reestablishing access to medications is challenging, we conditionally recommend against tapering. A patient decision aid was developed to complement the recommendation. This living guideline will provide contemporary RA management recommendations for Canadian practice. New recommendations will be added over time and updated, with the latest recommendation, evidence summaries, and Evidence to Decision summaries available through the CRA website (www.rheum.ca).

Long-term outcomes after discontinuing biological drugs and tofacitinib in patients with rheumatoid arthritis: A prospective cohort study.

This study examined long-term outcomes of biological disease-modifying antirheumatic drugs (bDMARDs) and tofacitinib discontinuation in patients with rheumatoid arthritis (RA). Ninety-seven RA patients who desired drug discontinuation after sustained remission or low disease activity for at least 48 weeks due to stable treatment with biological drugs or tofacitinib were enrolled into this study. All patients were prospectively followed until disease flare or the end of the study. Discontinued drugs (previous drugs) were reintroduced to treat flares. Following bDMARD/tofacitinib discontinuation (mean follow-up, 2.1 years; standard deviation, 2.0), disease flare occurred at a crude incidence rate of 0.36 per person-year. The median time to flare was 1.6 years (95% confidence interval [CI] 0.9-2.6), and the cumulative flare probability was estimated to be 45% at 1 year, 64% at 3 years, and 80% at 5 years. No or little radiological progression was shown in 87.1% of patients who maintained remission for 3 years. A Fine‒Gray competing risk regression analysis showed that predictive factors for a flare were longer RA duration at the start of bDMARD/tofacitinib treatment, previous failure of treatment with bDMARDs, and a shorter period of remission or low disease activity before drug discontinuation. Type of discontinued drug was not identified as a predictive factor after adjusting for other predictor variables. Restarting previous treatment regimens led to rapidly regaining disease control in 89% of flare patients within 1 month. Discontinuation of bDMARD/tofacitinib may be a feasible strategy in RA patients, especially patients with early treated and longer-controlled RA. Flares are manageable in most RA patients and radiological progression is rare for at least 3 years in patients with sustained remission after bDMARD/tofacitinib discontinuation.

Long-term Treatment With Ponesimod in Relapsing-Remitting Multiple Sclerosis: Results From Randomized Phase 2b Core and Extension Studies.

ObjectiveTo evaluate the dose-response relationship of 10, 20, and 40 mg ponesimod and long-term efficacy and safety of ponesimod 20 mg using an analysis of combined data from the phase 2 Core and Extension studies in patients with relapsing-remitting multiple sclerosis (RRMS).MethodsIn the Core study, 464 patients were randomized (1:1:1:1): placebo (n = 121), 10 mg (n = 108), 20 mg (n = 116), or 40 mg ponesimod (n = 119) once daily for 24 weeks. Patients who completed the Core study transitioned into the Extension study, which had treatment period 1 (TP1; up to 96 weeks) and TP2 and TP3 (up to 432 weeks). The 40 mg dose was discontinued due to low tolerability at the end of TP1, and the 10 mg dose was subsequently discontinued due to lower benefit-risk profile vs 20 mg at the end of TP2. All patients received 10 or 20 mg during TP2, followed by 20 mg in TP3. Annualized relapse rate (ARR), 6-month confirmed disability accumulation (CDA), time to first confirmed relapse, MRI outcomes, and safety were evaluated.ResultsA total of 435 patients received ≥1 dose of ponesimod (first randomized dose: 10 mg = 139, 20 mg = 145, and 40 mg = 151) at any time during the Core and/or the Extension study. As of March 31, 2019, 214 patients were still on ponesimod treatment. The median (range) of ponesimod exposure was 7.95 (0–9.36) years. Ponesimod 20 mg, from Core up to the end of TP3, was associated with sustained low clinical activity (ARR for confirmed relapses: 0.154; at week 432, Kaplan-Meier estimate for confirmed relapse was 43.9%, and 6-month CDA was 20.4%) and MRI disease activity, and over 64% of patients remained free of a confirmed relapse. Most common adverse events were nasopharyngitis (30%), headache (24%), and upper respiratory tract infection (21%).ConclusionThe effects on multiple sclerosis disease control were maintained with ponesimod 20 mg for approximately 8 years with no new safety concerns identified.Classification of EvidenceThis study provides Class IV evidence that in individuals with RRMS, long-term treatment with ponesimod 20 mg was associated with a sustained low annualized confirmed relapse rate (0.154 at week 432), with 64% of patients remaining relapse-free.Trial Registration InformationEudraCT Number 2008-006786-92 (Core study) and EudraCT Number 2009-011470-15 (Extension study).

OP0022 DISEASE ACTIVITY-GUIDED TAPERING OF BIOLOGICS IN PATIENTS WITH INFLAMMATORY ARTHRITIS: A RANDOMISED, OPEN-LABEL, EQUIVALENCE TRIAL

BackgroundTraditionally, biologics are maintained lifelong at standard dose in patients with inflammatory arthritis (IA) when sustained low disease activity (LDA) is reached. However, evidence of possible tapering is emerging but data on the optimal approach is lacking.ObjectivesThe primary outcomes at 18 months follow-up are:Superiority: The proportion of patients reduced to ≤50% of their baseline biologic dose.Equivalence: Disease activity (rheumatoid arthritis [RA] and psoriatic arthritis [PsA]: Disease Activity Score28-C-Reactive Protein [DAS28-CRP] and axial spondyloarthritis [axSpA]: Ankylosing Spondylitis Disease Activity Score [ASDAS]).MethodsThe BIODOPT trial was a randomised, open-label, equivalence trial (EudraCT 2017-001970-41). Eligible patients were adults with RA, PsA, or axSpA in LDA on stable biologic doses during ≥12 months. The randomisation ratio was 2:1 (tapering:continuation) stratified by diagnosis, centre, and repeated biologic failures. In the tapering group, the biologic dosing interval was prolonged by 25% every four months until flare or discontinuation. The continuation group was kept on their baseline biologic dosing interval; however, a small increase was allowed (as usual practise) if requested by the patient. The sample size calculation was based on a pre-defined equivalence margin of ±0.5 disease activity points (&lt;half of the minimal important difference in DAS28-CRP [&gt;1.2] or ASDAS [&gt;1.1]) yielding a power of 87% for 180 enrolled patients. All analyses were based on the intention-to-treat population. Continuous outcomes were analysed with repeated-measures linear mixed-effects models with group, diagnosis, centre, repeated biologic failures, time point, and the interaction between group and time as fixed factors and the baseline value of the relevant variable as a covariate. Categorical outcomes were analysed using logistic regression with missing data imputed as trial failures.ResultsBetween May, 2018, and March, 2020, 142 patients were enrolled of which 95 were randomised to tapering and 47 to continuation; inclusion was closed in April 2020 due to national implications of the coronavirus pandemic.At 18 months, significantly more patients in the tapering group (35 patients [(37%]) achieved a significant reduction in their biologic dose (≥50%) compared to the continuation group (one patient [2%]), absolute risk difference (RD) 35%, 95%CI: 24% to 45%, p&lt;0.0001, Table 1. Furthermore, disease activity at 18 months was within the equivalence margins of ±0.5, mean difference between groups 0.08, 95%CI: -0.12 to 0.29; Table 1 and Figure 1. Flares were more frequent in the tapering group (39 [41%] vs 10 [21%], RD 0.20, 95%CI: 0.04 to 0.35, p=0.011) but managed with rescue therapy (e.g. biologic dose escalation or glucocorticoids) as only one patient (1%) in the tapering group and three patients (6%) in the continuation group lost therapeutic response and were switched to another biological agent.Table 1.Comparison at 18 months in the ITT populationOutcomeTapering group N = 95Continuation group N = 47Group difference (95%CI)p-valuePrimary outcome:Biologics reduced to ≤50%, n (%)35 (37%)1 (2%)0.35 (0.24 to 0.45)&lt;0.001Disease activity, LSMeans (SE)1.84 (0.15)1.75 (0.16)0.08 (-0.12 to 0.29)0.428Key secondary outcomes:Remission1, n (%)63 (66%)33 (70%)-0.04 (-0.20 to 0.12)0.637Low disease activity2, n (%)79 (83%)41 (87%)-0.04 (-0.16 to 0.08)0.511Flares3, n (%)39 (41%)10 (21%)0.20 (0.04 to 0.35)0.011N: number, CI: confidence interval, LSMeans: Least squares means, SE: Standard error.1: RA or PsA: DAS28-CRP &lt;2.6. AxSpA: ASDAS &lt;1.3.2: RA or PsA: DAS28-CRP &lt;3.2. AxSpA: ASDAS &lt;2.1.3: RA or PsA: ΔDAS28-CRP &gt;1.2 or ΔDAS28-CRP &gt;0.6 AND current DAS28-CRP ≥3.2. AxSpA: inflammatory back pain AND ΔASDAS ≥0.9 and/or ≥1 swollen joint.ConclusionAcross IA conditions, a significant reduction of biologic dose is possible with disease activity-guided tapering while maintaining a similar disease activity state compared to continuation of biologic as usual care.AcknowledgementsThe authors thank patients, research personnel, and the patient research partners for their contribution to the BIODOPT trial, data manager JHW for technical support and for uploading the concealed allocation sequence, and CCH for data management. The Parker Institute, Bispebjerg and Frederiksberg Hospital is supported by a core grant from the Oak Foundation (OCAY-18-774-OFIL).Disclosure of InterestsLine Uhrenholt Speakers bureau: Abbvie, Eli Lilly, Janssen, and Novartis, Robin Christensen: None declared, Lene Dreyer Speakers bureau: Eli Lilly, Galderma and Janssen, Grant/research support from: BMS (outside the present work), Ellen-Margrethe Hauge Speakers bureau: AbbVie, Sanofi, Sobi, and SynACT Pharma, Grant/research support from: Roche, Novartis, and Novo Nordic Foundation (outside the present work), Annette Schlemmer Speakers bureau: Eli Lilly, Anne Gitte Loft Speakers bureau: AbbVie, MSD, Novartis and UCB, Consultant of: Eli-Lilly, Janssen-Cilag, MSD, Novartis, and UCB, Mads Nyhuus Bendix Rasch Speakers bureau: Sobi, Hans Christian Horn: None declared, Katrine Gade: None declared, Peter C. Taylor Consultant of: AbbVie, Biogen, Eli Lilly, Fresenius, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer Inc, Roche, and Sanofi, Grant/research support from: Celgene, and Galapagos (outside the present work), Salome Kristensen: None declared.

POS1356 TREATMENT OF IMMUNE CHECKPOINT INHIBITOR-INDUCED INFLAMMATORY ARTHRITIS AND POLYMYALGIA RHEUMATICA

BackgroundTherapy with immune check point inhibitors (ICIs) has revolutionized cancer treatment during the last years. Despite their high efficacy, ICIs are associated to a new spectrum of adverse events, the immune-related adverse events (irAEs). Inflammatory arthritis and polymyalgia rheumatica (PMR) are two of the most common rheumatic irAEs. The optimal management of irAEs remains unclear. Treatment guidelines largely support the use of glucocorticoids (GCs) as first line therapy [1]. Preclinical data raise concerns regarding the potential risk of impaired antitumoral effect with use of GCs. The high efficacy and potential synergistic effect (according to recent findings) [2] of targeted immunomodulation, such as interleukin 6 (IL-6) blockade, could support a paradigm shift, where targeted treatments are considered earlier in the treatment sequence.ObjectivesTo assess how frequently a disease modifying anti-rheumatic drug (DMARD) treatment in patients with ICI induced arthritis and/or PMR, after inadequate response to GCs, is initiated and to assess its effectiveness.MethodsWe retrospectively identified patients who were diagnosed with inflammatory arthritis and/or PMR at the rheumatology department at Karolinska University Hospital, after referral from the oncology department due to suspicion of a rheumatic irAE, between Jan 2020 and Dec 2021. Treatment response was defined as sustained low disease activity or remission according to the rheumatologist evaluation at 6 months (+/- 1 month) after initiation of DMARD.ResultsA total of 20 patients were identified, who were diagnosed with arthritis (N=11), PMR (N=6) or both (N=3). The median (IQR) age was 70 (46-76) years; 50% of patients were females. The type of cancer was urogenital (N=8), melanoma (N=6), lung cancer (N=2), and other (N=4). 14 patients received a PD-1 inhibitor (9 nivolumab, 4 pembrolizumab, 1 cemiplimab), 3 received a PDL-1 inhibitor (2 atezolizumab, 1 avelumab), 2 received a combination of nivolumab and the CTLA-4 inhibitor ipilimumab and one patient combination of nivolumab and pembrolizumab. The median time from start of ICI treatment to symptom debut was 2 (1.25-3.75) months.83% of patients with PMR and/or arthritis responded well to GCs without the need for treatment escalation. On the contrary,11 out of 14 patients (79%) with inflammatory arthritis (with or without PMR) responded inadequately to GC treatment, despite receiving moderate-high doses (median 20mg/day Prednisolone or equivalent), or flared when the dose was reduced below 10mg/day. A conventional synthetic DMARD was initiated in 7 patients (methotrexate N=6, hydroxychloroquine N=1), with a response rate of 71%. 3 patients received a biologic DMARD as first-line DMARD, either because of contraindication for methotrexate and/or high disease activity, and 2 patients after methotrexate failure. All 5 patients tocilizumab, with a response rate of 100%. Subsequently 1 of these patients discontinued tocilizumab due to suspected side effects, and started with a TNF inhibitor. After initiation of tocilizumab all patients were able to reduce the dose of GCs to less than 5mg/day.ConclusionThe majority of patients developing ICI-induced arthritis are refractory to GCs and need a DMARD treatment, although selection bias cannot be formally excluded, since the most severe forms of arthritis might be referred to the rheumatology department. csDMARDs are effective in a significant proportion of patients. Tocilizumab is highly effective and well tolerated in ICI-induced arthritis. ICI-induced PMR seems to respond adequately to GCs.

AB0333 SUSTAINABILITY OF RESPONSE TO UPADACITINIB AMONG PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS REFRACTORY TO BIOLOGICAL DISEASE-MODIFYING ANTI-RHEUMATIC DRUGS

BackgroundSustained clinical remission (REM) is the primary treatment goal for patients with rheumatoid arthritis (RA), with low disease activity (LDA) being an appropriate target for treatment-refractory patients.1,2ObjectivesTo evaluate the sustainability of response to the JAK inhibitor, upadacitinib (UPA) 15 mg once daily (QD), among patients with prior inadequate response or intolerance to biologic DMARDs.MethodsData come from the 12-week, phase 3 randomized, placebo (PBO)-controlled SELECT-BEYOND trial of UPA 15 mg or 30 mg QD in patients with moderate to severe RA on stable background conventional synthetic (cs) DMARDs. Initiation, change, or discontinuation of background RA medications, including ≤2 csDMARDs, was allowed starting at Week 24. Patients completing the 12-week trial were able to enter a long-term extension of up to 5 yrs with all PBO patients switching to UPA.3 This post hoc analysis evaluated REM (CDAI ≤2.8; SDAI ≤3.3), LDA (CDAI≤10; SDAI≤11), and DAS28(CRP) &lt;2.6/≤3.2 at first occurrence of response before Week 60, as well as at 3, 6, and 12 months following initial response in patients randomized to UPA 15 mg. For those patients who achieved REM/LDA, Kaplan-Meier was used to define the time from when the response was first achieved to the earliest date at which the response was lost at two consecutive visits or discontinuation of study drug. The predictive ability of time to REM/LDA was evaluated using Harrell’s concordance (c)-index (range: 0 to 1, where 0.5 indicates a model that is no better at predicting an outcome than random chance). The date of the last follow up was 16 April 2018, when all patients had reached the Week 60 visit. Non-responder imputation was used for missing data. Only data from the approved 15 mg dosage are reported here.ResultsIn patients with active RA despite prior treatment with at least one bDMARD, 34% and 79% of those receiving UPA 15 mg + background csDMARD(s) achieved CDAI REM or LDA through Week 60, respectively. Sustained CDAI REM was attained by 30%, 26%, and 16% of patients randomized to UPA at 3, 6, and 12 months post initial response, while CDAI LDA was achieved by 68%, 61%, and 50% of patients during the same time points (Figure 1). Time to initial clinical response weakly predicted sustained REM but did not predict sustained LDA, with a c-index (95% CI) of 0.62 (0.49, 0.74) and 0.52 (0.44, 0.61), respectively. Through the last follow-up visit at Week 60, 39/61% of patients on UPA remained in CDAI REM/LDA (Figure 2). Of those who lost CDAI REM, 58% remained in CDAI LDA, and 22% recaptured REM by the cut-off date; 18% of patients who lost CDAI LDA recaptured response. Similar results were observed for REM and LDA based on SDAI and for DAS28(CRP) &lt;2.6/≤3.2.ConclusionAmong patients with inadequate response or intolerance to bDMARDs, over three-quarters on UPA 15 mg achieved CDAI LDA, a relevant therapeutic target for these treatment-refractory patients, and nearly two-thirds of those maintained this response through 60 weeks. Additionally, about one-third of UPA-treated patients attained CDAI REM and maintained that response over 60 weeks.

P258 Secukinumab Improves Physical Function and Inhibits Structural Damage in Psoriatic Arthritis PsA Patients With Sustained Remission or Low Disease Activity: Results From a Phase 3 Study

Abstract Background/Aims Disease Activity Index for Psoriatic Arthritis (DAPSA) or the minimal disease activity (MDA) are considered for defining remission (REM) or low disease activity (LDA) in secukinumab-treated patients with psoriatic arthritis (PsA). Currently, limited secukinumab data are available on patients with PsA achieving sustained REM in clinical trials or real-world evidence using these stringent criteria. This abstract reports an exploratory analysis of achievement of sustained REM/LDA in patients with PsA treated with secukinumab and impact on structural outcomes, physical function and health-related quality of life (HRQoL) in the FUTURE 5 study (NCT02404350). Methods FUTURE 5 is a randomised, double-blind, placebo-controlled, 2-year phase 3 trial in patients with active PsA. Patients randomised to secukinumab 150 mg could be escalated to 300 mg from week 52 to 104, based on investigators’ judgement. Patients were categorised as either not achieving REM/LDA, achieving it once only, or sustained REM/LDA (defined as patients achieving REM/LDA between weeks 24-52 and maintaining the same response at least 2 of the next 6 visits [visit every 8 weeks]). Of patients who did not achieve REM/LDA or who achieved REM/LDA (VLDA, DAPSA REM, MDA, DAPSA LDA+REM) between weeks 24 and 52, the relationships between: absence of REM/LDA; REM/LDA; sustained REM/LDA; proportion of patients with non-radiographic progression (assessed using the van der Heijde [mTSS]); physical function (health assessment questionnaire disability index [HAQ-DI]); and short form-36 physical component score [SF-36 PCS]) were assessed. Results 996 patients were randomised to 1 of 4 treatment groups: secukinumab 300 mg loading dose (LD; n = 222), secukinumab 150 mg LD (n = 220), secukinumab 150 mg no LD (NL; n = 222), and placebo (n = 332). The baseline clinical characteristics were comparable across treatment groups. Most patients achieved either sustained MDA or sustained DAPSA LDA+REM (Table). Patients achieving REM/LDA, whether at one visit or consistently, showed improved physical function and SF36-PCS at week 104. A high proportion of patients did not show radiographic progression at week 104 irrespective of achievement of REM/LDA category. Conclusion Most patients treated with secukinumab achieved a sustained LDA. Sustained LDA/REM was associated with improved HRQoL, physical function and inhibition of structural damage progression. Disclosure L.C. Coates: Consultancies; Abbvie, Amgen, Biogen, Boehringer Ingelheim, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, UCB. Grants/research support; Abbvie, Celgene, Lilly, Novartis, Pfizer. P.J. Mease: Consultancies; AbbVie, Amgen, BMS, Boehringer Ingelheim, Galapagos, Celgene, GlaxoSmithKline, Gilead, Janssen, Lilly, Novartis, Pfizer, SUN Pharma, UCB. Member of speakers’ bureau; AbbVie, Amgen, Janssen, Lilly, Novartis, Pfizer, UCB. Grants/research support; AbbVie, Amgen, BMS, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, SUN, UCB. D.D. Gladman: Consultancies; Abbvie, Amgen, BMS, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Novartis, Pfizer, UCB. Grants/research support; Abbvie, Amgen, Celgene, Eli Lilly, Novartis, Pfizer, UCB. S. Navarra: Consultancies; Pfizer, Novartis, Astra-Zeneca, Janssen, Lilly, Astellas. Member of speakers’ bureau; Pfizer, Novartis, Astra-Zeneca, Janssen, Lilly, Astellas. W. Bao: Shareholder/stock ownership; Novartis. Other; Employee of Novartis. C. Gaillez: Shareholder/stock ownership; Novartis, BMS. Other; Employee of Novartis.

Sustained low disease activity measured by ASDAS slow radiographic spinal progression in axial spondyloarthritis patients treated with TNF-inhibitors: data from REGISPONSERBIO

BackgroundTo evaluate the influence of the disease activity on radiographic progression in axial spondyloarthritis (axSpA) patients treated with TNF inhibitors (TNFi).MethodsThe study included 101 axSpA patients from the Spanish Register of Biological Therapy in Spondyloarthritides (REGISPONSERBIO), which had clinical data and radiographic assessment available. Patients were classified into 2 groups based on the duration of TNFi treatment at baseline: (i) long-term treatment (≥4 years) and (ii) no long-term treatment (< 4 years). Radiographs were scored by two readers according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) with known chronology. Disease activity differences between patients’ groups at each time point were assessed using a linear mixed-effect model.ResultsRadiographic progression was defined as an increase in ≥2 mSASSS units. At inclusion, approximately half of the patients (45.5%) were receiving long-term treatment with TNFi (≥4 years). In this group of subjects, a significant difference in averaged Ankylosing Spondylitis disease Activity Score (ASDAS) across follow-up was found between progressors and non-progressors (2.33 vs 1.76, p=0.027, respectively). In patients not under long-term TNFi treatment (54.5%) though, no significant ASDAS differences were observed between progressors and non-progressors until the third year of follow-up. Furthermore, no significant differences were found in progression status, when disease activity was measured by Bath Ankylosing spondylitis Disease Activity Index (BASDAI) and C reactive protein (CRP).ConclusionsPatients on long-term TNFi treatment with a mean sustained low disease activity measures by ASDAS presented lower radiographic progression than those with active disease.

Defining the relationship between pain intensity and disease activity in patients with rheumatoid arthritis: a secondary analysis of six studies

BackgroundPain is the main concern of patients with rheumatoid arthritis (RA) while reducing disease activity dominates specialist management. Disease activity assessments like the disease activity score for 28 joints with the erythrocyte sedimentation rate (DAS28-ESR) omit pain creating an apparent paradox between patients’ concerns and specialists’ treatment goals. We evaluated the relationship of pain intensity and disease activity in RA with three aims: defining associations between pain intensity and disease activity and its components, evaluating discordance between pain intensity and disease activity, and assessing temporal changes in pain intensity and disease activity.MethodsWe undertook secondary analyses of five trials and one observational study of RA patients followed for 12 months. The patients had early and established active disease or sustained low disease activity or remission. Pain was measured using 100-mm visual analogue scales. Individual patient data was pooled across all studies and by types of patients (early active, established active and established remission). Associations of pain intensity and disease activity were evaluated by correlations (Spearman’s), linear regression methods and Bland-Altman plots. Discordance was assessed by Kappa statistics (for patients grouped into high and low pain intensity and disease activity). Temporal changes were assessed 6 monthly in different patient groups.ResultsA total of 1132 patients were studied: 490 had early active RA, 469 had established active RA and 173 were in remission/low disease activity. Our analyses showed, firstly, that pain intensity is associated with disease activity in general, and particularly with patient global assessments, across all patient groups. Patient global assessments were a reasonable proxy for pain intensity. Secondly, there was some discordance between pain intensity and disease activity across all disease activity levels, reflecting similar discrepancies in patient global assessments. Thirdly, there were strong temporal relationships between changes in disease activity and pain intensity. When mean disease activity fell, mean pain intensity scores also fell; when mean disease activity increased, there were comparable increases in pain intensity.ConclusionsThese findings show pain intensity is an integral part of disease activity, though it is not measured directly in DAS28-ESR. Reducing disease activity is crucial for reducing pain intensity in RA.

Recommendations of the Brazilian Society of Rheumatology for the use of JAK inhibitors in the management of rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic and autoimmune systemic inflammatory disease that can cause irreversible joint deformities, with increased morbidity and mortality and a significant impact on the quality of life of the affected individual. The main objective of RA treatment is to achieve sustained clinical remission or low disease activity. However, up to 40% of patients do not respond to available treatments, including bDMARDs. New therapeutic targets for RA are emerging, such as Janus kinases (JAKs). These are essential for intracellular signaling (via JAK-STAT) in response to many cytokines involved in RA immunopathogenesis. JAK inhibitors (JAKi) have established themselves as a highly effective treatment, gaining increasing space in the therapeutic arsenal for the treatment of RA. The current recommendations aim to present a review of the main aspects related to the efficacy and safety of JAKis in RA patients, and to update the recommendations and treatment algorithm proposed by the Brazilian Society of Rheumatology in 2017.

Switching from TNF\u03b1 inhibitor to tacrolimus as maintenance therapy in rheumatoid arthritis after achieving low disease activity with TNF\u03b1 inhibitors and methotrexate: 24-week result from a non-randomized, prospective, active-controlled trial

BackgroundTapering or stopping biological disease-modifying anti-rheumatic drugs has been proposed for patients with rheumatoid arthritis (RA) in remission, but it frequently results in high rates of recurrence. This study evaluates the efficacy and safety of tacrolimus (TAC) as maintenance therapy in patients with established RA in remission after receiving combination therapy with tumor necrosis factor inhibitor (TNFi) and methotrexate (MTX).MethodsThis 24-week, prospective, open-label trial included patients who received TNFi and MTX at stable doses for ≥24 weeks and had low disease activity (LDA), measured by Disease Activity Score-28 for ≥12 weeks. Patients selected one of two arms: maintenance (TNFi plus MTX) or switched (TAC plus MTX). The primary outcome was the difference in the proportion of patients maintaining LDA at week 24, which was assessed using a logistic regression model. Adverse events were monitored throughout the study period.ResultsIn efficacy analysis, 80 and 34 patients were included in the maintenance and switched arms, respectively. At week 24, LDA was maintained in 99% and 91% of patients in the maintenance and switched arms, respectively (odds ratio, 0.14; 95% confidence interval, 0.01–1.59). Drug-related adverse effects tended to be more common in the switched arm than in the maintenance arm (20.9% versus 7.1%, respectively) but were well-tolerated.ConclusionThis controlled study tested a novel treatment strategy of switching from TNFi to TAC in RA patients with sustained LDA, and the findings suggested that TNFi can be replaced with TAC in most patients without the patients experiencing flare-ups for at least 24 weeks.Trial registrationKorea CDC CRIS, KCT0005868. Registered 4 February 2021—retrospectively registered

Quality indicators for systemic lupus erythematosus based on the 2019 EULAR recommendations: development and initial validation in a cohort of 220 patients

BackgroundQuality of care is receiving increased attention in systemic lupus erythematosus (SLE). We developed quality indicators (QIs) for SLE based on the 2019 update of European League Against Rheumatism recommendations.MethodsA...

P132 Redefining refractory disease in RA and adult polyarticular JIA: a Delphi consensus study

Abstract Background/Aims Patients who do not achieve sustained low disease activity despite drug treatments are referred to as having refractory disease. However, usage of this term varies and often does not account for any discrepancy between inflammation and persistent symptoms, adult or juvenile onset nor differences between patients’ and healthcare professionals’ perspectives. The study aimed to explore and achieve consensus on a definition of refractory disease across healthcare professionals and patients, through a mixed-methods Delphi approach. Methods Three rounds of voting (one face-to-face nominal group (n = 13), and two online rounds (ns = 40 and 53)) were conducted, in conjunction with the National Rheumatoid Arthritis Society. Participants voted on the inclusion and relevance of statements to generate a broader definition of refractory disease, derived from previous qualitative interviews with multi-disciplinary healthcare professionals and patients (adult and juvenile onset), a systematic review of current definitions and health psychology theory. The process involved voting on: a) name preferences, b) treatment and inflammation statements, c) domains for inclusion regarding symptoms and impact, and d) rating of individual components within each domain, including relevance to: i) Refractory Arthritis and ii) Disease Flare for discriminatory validity. A predetermined cut off was applied to identify which domains needed to be included, until final consensus was reached. Full NHS ethical approval was granted (London-Hampstead-18/LO/1171). Results With minimal attrition (n = 3 in both online rounds), 106 international participants including Patient Representatives, Rheumatologists, Nurses, GPs, Psychologists, Physiotherapists, Researchers, Pharmacist, Podiatrist, Occupational Therapist and a Social Worker participated. Refractory Inflammatory Arthritis was the most popular name, (25% of votes) followed by Persistent Inflammatory Arthritis (19% of votes) hence its application in the presence (Persistent Inflammation) or absence (Persistent Symptoms) of inflammation as part of the definition. Regarding treatment and inflammation, these were voted in the majority to be kept broad rather than specifying rigid cut-offs. From the original 73 components across 10 domains identified to capture symptoms and impact, initial analysis has resulted in six domains reaching consensus for inclusion. These domains cover: 1) Disease Activity, 2) Joint Involvement, 3) Pain, 4) Fatigue, 5) Functioning and Quality of Life, and 6) cs/b/tsDMARD Experiences. Within these, 18 components were identified as related and important e.g. One or two persistently active/affected joints, Reduced mobility, Disease-related Distress, Inability to perform desired activities, Repeated need of short course steroids and Disease Activity not captured by DAS28. These capture the multi-faceted presentation and experience of Refractory Inflammatory Arthritis in these two populations. Conclusion A broader definition for refractory inflammatory arthritis has been generated through a Delphi method to capture the experiences of rheumatologists, patients and multi-disciplinary healthcare professionals. This definition needs further refinement and validation to assess clinical and research utility to identify high risk patients with unmet needs. Disclosure H. Chaplin: None. A. Bosworth: None. J. Meehan: None. R. Moss-Morris: None. H. Lempp: None. S. Norton: None.