Achievement Of Low Disease Activity Research Articles

Tumour necrosis factor inhibitor tapering in patients with ankylosing spondylitis at low disease activity: factors associated with flare.

Background:To investigate factors associated with flare in patients with ankylosing spondylitis (AS) who tapered tumour necrosis factor inhibitors (TNFis) after achievement of low disease activity (LDA) with the standard dose of TNFis.Methods:This retrospective cohort study included 101 patients with AS who tapered their first TNFis after achievement of LDA. The proportion of reduced versus standard doses of TNFi throughout the follow up in each patient was quantified using the time-averaged dose quotient (DQ). Clinical characteristics were compared between patients who did and did not experience flare after TNFi tapering. Multivariable Cox regression analysis was performed to identify factors associated with flare. Receiver operating characteristic curve analysis was performed to determine the cut-offs of these covariates that best predicted flare.Results:Of the total 101 patients, 45 (44.6%) patients experienced flare after TNFi tapering. Compared with patients who did not experience flare, those who experienced flare had a shorter disease duration (p = 0.006), shorter LDA duration before TNFi tapering (p < 0.001) and lower time-averaged DQ (p < 0.001). In multivariable Cox regression analysis, the LDA duration [adjusted hazard ratio (HR): 0.944, 95% confidence interval (CI): 0.906–0.983, p = 0.006] and time-averaged DQ (adjusted HR: 0.978, 95% CI: 0.959–0.998, p = 0.032) were inversely associated with flare. The cut-off values of the LDA duration and time-averaged DQ that best predicted flares were <5.3 months and <60.6%, respectively.Conclusion:Shorter LDA duration (cut-off value: 5.3 months) and lower time-averaged DQ (cut-off value: 60.6%) were associated with a higher risk of flare after tapering TNFi.

Limiting factors to Boolean remission differ between autoantibody-positive and -negative patients in early rheumatoid arthritis.

Background:The patient global assessment of disease activity (PGA) is the major limiting factor to Boolean remission in patients with established rheumatoid arthritis (RA). Here, we investigated the limiting variables to disease remission in patients with early RA treated with conventional synthetic disease modifying anti-rheumatic drugs, also in relation to autoantibody status.Methods:Data were retrieved from 535 early RA patients (<12 months of symptoms) with an observation period of 6–12 months upon initiation of therapy with methotrexate aimed at the achievement of low disease activity based on the 28-joints disease activity score. Near-remission was defined as any of the four core items of Boolean remission >1 with the remaining three all ⩽1. Reasons for missing Boolean remission and predictors of near-remission subcategories were analyzed in relation to baseline disease variables.Results:After 6 and 12 months, near-remission was two-times more frequent than Boolean remission (25.6% and 26.9% at the two time-points). A 28-swollen joint count (SJC28) >1 was responsible for the majority of near-remission (56.2% and 57.6% at 6 and 12 months, respectively), and PGA > 1 accounted for approximatively 35% of the cases. Autoantibody-positivity independently predicted the risk of missing remission because of SJC28 > 1 [adjusted odds ratio (OR) 95% confidence interval (CI) 2.81 (1.59–4.9) at 6 months and 1.73 (1.01–3.01) at 12 months], whilst autoantibody-negativity was an independent predictor of PGA near-remission [adjusted OR (95% CI) 2.45 (1.25–4.80) at 6 months and 5.71 (2.47–13.2) at 12 months].Conclusion:In early RA, Boolean remission is more frequently missed because of persistent swollen joints. However, barriers to full-remission vary in relation to the autoantibody status. Autoantibody-positive patients more commonly experience residual swollen joints, whilst PGA more frequently impairs remission in autoantibody-negative patients. Efforts to target full-remission in early RA may thus require different strategies according to autoantibody profile.

Predictors for clinical effectiveness of baricitinib in rheumatoid arthritis patients in routine clinical practice: data from a Japanese multicenter registry

This study aimed to evaluate the short-term effectiveness and safety profiles of baricitinib and explore factors associated with improved short-term effectiveness in patients with rheumatoid arthritis (RA) in clinical settings. A total of 113 consecutive RA patients who had been treated with baricitinib were registered in a Japanese multicenter registry and followed for at least 24 weeks. Mean age was 66.1 years, mean RA disease duration was 14.0 years, 71.1% had a history of use of biologics or JAK inhibitors (targeted DMARDs), and 48.3% and 40.0% were receiving concomitant methotrexate and oral prednisone, respectively. Mean DAS28-CRP significantly decreased from 3.55 at baseline to 2.32 at 24 weeks. At 24 weeks, 68.2% and 64.1% of patients achieved low disease activity (LDA) and moderate or good response, respectively. Multivariate logistic regression analysis revealed that no previous targeted DMARD use and lower DAS28-CRP score at baseline were independently associated with achievement of LDA at 24 weeks. While the effectiveness of baricitinib was similar regardless of whether patients had a history of only one or multiple targeted DMARDs use, patients with previous use of non-TNF inhibitors or JAK inhibitors showed lower rates of improvement in DAS28-CRP. The overall retention rate for baricitinib was 86.5% at 24 weeks, as estimated by Kaplan–Meier analysis. The discontinuation rate due to adverse events was 6.5% at 24 weeks. Baricitinib significantly improved RA disease activity in clinical practice. Baricitinib was significantly more effective when used as a first-line targeted DMARDs.

Continuing versus tapering glucocorticoids after achievement of low disease activity or remission in rheumatoid arthritis (SEMIRA): a double-blind, multicentre, randomised controlled trial

Patients with inflammatory diseases, such as rheumatoid arthritis, often receive glucocorticoids, but long-term use can produce adverse effects. Evidence from randomised controlled trials to guide tapering of oral glucocorticoids is scarce. We investigated a scheme for tapering oral glucocorticoids compared with continuing low-dose oral glucocorticoids in patients with rheumatoid arthritis. The Steroid EliMination In Rheumatoid Arthritis (SEMIRA) trial was a double-blind, multicentre, two parallel-arm, randomised controlled trial done at 39 centres from six countries (France, Germany, Italy, Russia, Serbia, and Tunisia). Adult patients with rheumatoid arthritis receiving tocilizumab and glucocorticoids 5-15 mg per day for 24 weeks or more were eligible for inclusion if they had received prednisone 5 mg per day for 4 weeks or more and had stable low disease activaity, confirmed by a Disease Activity Score for 28 joints-erythrocyte sedimentation rate (DAS28-ESR) of 3·2 or less 4-6 weeks before and on the day of randomisation. Patients were randomly assigned 1:1 to either continue masked prednisone 5 mg per day for 24 weeks or to taper masked prednisone reaching 0 mg per day at week 16. All patients received tocilizumab (162 mg subcutaneously every week or 8 mg/kg intravenously every 4 weeks) with or without csDMARDs maintained at stable doses during the entire 24-week study. The primary outcome was the difference in mean DAS28-ESR change from baseline to week 24, with a difference of more than 0·6 defined as clinically relevant between the continued-prednisone group and the tapered-prednisone group. The trial is registered with ClinicalTrials.gov, NCT02573012. Between Oct 21, 2015, and June 9, 2017, 421 patients were screened and 259 (200 [77%] women and 59 [23%] men) were recruited onto the trial. In all 128 patients assigned to the continued-prednisone regimen, disease activity control was superior to that in all 131 patients assigned to the tapered-prednisone regimen; the estimated mean change in DAS28-ESR from baseline to week 24 was 0·54 (95% CI 0·35-0·73) with tapered prednisone and -0·08 (-0·27 to 0·12) with continued prednisone (difference 0·61 [0·35-0·88]; p<0·0001), favouring continuing prednisone 5 mg per day for 24 weeks. Treatment was regarded as successful (defined as low disease activity at week 24, plus absence of rheumatoid arthritis flare for 24 weeks and no confirmed adrenal insufficiency) in 99 (77%) patients in the continued-prednisone group versus 85 (65%) patients in the tapered-prednisone group (relative risk 0·83; 95% CI 0·71-0·97). Serious adverse events occurred in seven (5%) patients in the tapered-prednisone group and four (3%) patients in the continued-prednisone group; no patients had symptomatic adrenal insufficiency. In patients who achieved low disease activity with tocilizumab and at least 24 weeks of glucocorticoid treatment, continuing glucocorticoids at 5 mg per day for 24 weeks provided safe and better disease control than tapering glucocorticoids, although two-thirds of patients were able to safely taper their glucocorticoid dose. F Hoffmann-La Roche.

Tapering glucocorticoids in rheumatoid arthritis

Glucocorticoids are a cornerstone of care for patients with rheumatoid arthritis. Since the 1950s, glucocorticoids have been used to reduce inflammation and symptoms of arthritis, improve physical function, and reduce disability. These drugs are widely available, inexpensive, and typically combined with disease-modifying antirheumatic drugs to induce remission in rheumatoid arthritis. However, the administration of glucocorticoids is not without risk. Long-term use of glucocorticoids is associated with increased mortality, 1 Chester Wasko M Dasgupta A Ilse Sears G Fries JF Ward MM Prednisone use and risk of mortality in patients with rheumatoid arthritis: moderation by use of disease-modifying antirheumatic drugs. Arthritis Care Res. 2016; 68: 706-710 Crossref PubMed Scopus (32) Google Scholar cardiovascular events, 2 Roubille C Richer V Starnino T et al. The effects of tumour necrosis factor inhibitors, methotrexate, non-steroidal anti-inflammatory drugs and corticosteroids on cardiovascular events in rheumatoid arthritis, psoriaznn. Rheum Dis. 2015; 74: 480-489 Crossref PubMed Scopus (512) Google Scholar and bone fractures. 3 Tong JJ Xu SQ Zong HX Pan MJ Teng YZ Xu JH Prevalence and risk factors associated with vertebral osteoporotic fractures in patients with rheumatoid arthritis. Clin Rheumatol. 2020; 39: 357-364 Crossref PubMed Scopus (20) Google Scholar For this reason, rheumatoid arthritis management guidelines advocate using low-dose glucocorticoids (≤10 mg daily of a prednisone equivalent) during the initiation of a new disease-modifying antirheumatic drug and for a relatively short duration (<3 months) when treating a flare. 4 Singh JA Saag KG Bridges SL et al. 2015 American college of rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol. 2016; 68: 1-26 Crossref PubMed Scopus (2102) Google Scholar , 5 Smolen JS Landewé R Bijlsma J et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis. 2017; 76: 960-977 Crossref PubMed Scopus (1714) Google Scholar Continuing versus tapering glucocorticoids after achievement of low disease activity or remission in rheumatoid arthritis (SEMIRA): a double-blind, multicentre, randomised controlled trialIn patients who achieved low disease activity with tocilizumab and at least 24 weeks of glucocorticoid treatment, continuing glucocorticoids at 5 mg per day for 24 weeks provided safe and better disease control than tapering glucocorticoids, although two-thirds of patients were able to safely taper their glucocorticoid dose. Full-Text PDF

OP0040 ANTI-CITRULLINATED PROTEIN AUTOANTIBODIES ARE ASSOCIATED WITH ONGOING SYSTEMIC BONE LOSS IN PATIENTS WITH EARLY RHEUMATOID ARTHRITIS TREATED ACCORDING TO THE PRINCIPLES OF TREAT-TO-TARGET AND TIGHT-CONTROL

Background:Anti-citrullinated protein antibodies (ACPA) are a major risk factor for local and systemic bone loss in patients with rheumatoid arthritis (RA). We previously demonstrated that early RA patients at disease presentation already show reduced systemic bone mineral density (BMD) in association with ACPA-positivity (1). Whether the negative impact of ACPA on bone continues over time despite treatment institution is however unknown.Objectives:To investigate longitudinally the course of systemic bone loss in patients with early RA after institution of treatment with disease modifying anti-rheumatic drugs (DMARDs) according to the principles of treat-to-target and tight-control.Methods:The study population included 100 consecutive early RA patients (&lt;12 months of symptoms) recruited at our Early Arthritis inception cohort and already evaluated for systemic BMD at disease presentation before treatment start (1). After diagnosis, patients were prospectively followed-up at three-months intervals upon initiation of therapy with conventional synthetic DMARDs (methotrexate in 85% of the cases) aimed at the achievement of low disease activity (LDA, 28-joints disease activity score [DAS28] &lt;3.2). BMD was re-assessed after 24 months at the lumbar spine (L1-L4) and hip by the same dual X-ray absorptiometry (DXA) equipment used at baseline. Differences in BMD from baseline were evaluated in relation to demographic and clinical variables (listed in Table 1).Table.Predictors of bone mineral density changes over 24 months% change in BMDlumbar spinetotal hipfemoral neckrprprpAge0.2690.0080.0690.500.2580.01female gender0.0850.42-0.0230.54-0.1210.23menopause0.1370.200.0670.530.0870.41disease duration0.0740.470.0440.670.0160.87cumulative DAS280.0180.860.0020.870.0110.91time to LDA0.1420.16-0.0230.76-0.0440.66time to remission0.0350.74-0.0020.97-0.0110.91ACPA-0.2510.010.1260.22-0.1300.04RF-0.1130.270.1110.280.0010.99months of bisphosphonates0.3680.0030.1710.090.2910.04cumulative steroids-0.1430.16-0.0070.78-0.0090.93months of bDMARDs-0.1630.11-0.0540.48-0.0630.54Results:The study population was mainly composed of females (84%), of whom 64.3% were in post-menopause; the mean (SD) age was 57.4 (13.5) years. Median (IQR) symptoms duration before treatment start was 14 (9-24) weeks. Fourty-three percent of the patients was ACPA positive. After 24 months of treatment, LDA was achieved in 79% of the cases, and remission in 46%; 17.7% of the patients had initiated a biological DMARD. At DXA re-scanning, the BMD at the lumbar spine and total hip remained largely unchanged, whilst at the femoral neck decreased from 0.726 g/cm2 to 0.713 g/cm2 (mean difference [SD] -0.013 [0.056], p=0.02). Predictors of BMD changes at different sites are shown in Table 1. The cumulative dose of prednisone was borderline significant for more BMD loss at the lumbar spine. Cumulative disease activity did not significantly affect BMD changes. Rather, ACPA-positive patients had higher percent changes at both the lumbar spine and the femoral neck. In multivariable analyses, ACPA remained associated with more BMD loss even when adjusting for confounders (age, gender, cumulative steroids, bisphosphonate treatment) (r -0.126, p=0.04 at the lumbar spine; r -0.126, p=0.04 at the femoral neck).Conclusion:Treatment of patients with early RA according to treat-to-target strategies prevents systemic bone loss. However, despite optimal disease control, ACPA positivity continues to be associated with progressive decline in systemic BMD.

SAT0435 SECUKINUMAB EFFICACY In PsA PATIENTS IS DEPENDENT ON PATIENTS’ BODY MASS INDEX

Background:Psoriatic arthritis (PsA) is a chronic inflammatory arthritis burdened by a series of metabolic comorbidities. Among them, obesity is very common in PsA, with a prevalence of 27%, as confirmed by a recent Spanish work (1). Obesity in PsA has been associated with higher disease activity and a worse effectiveness of biologic treatment in PsA. This has been certainly proven for anti-TNF-α as demonstrated by different studies reporting, in obese patients, a reduced treatment response and adherence. In particular, results coming from DAN-BIO and ICE-BIO registries, (2) point out that obesity is a risk factor for anti-TNF withdrawal due to poor response. Although a recent multi-centric, retrospective study in Spain has shown that obese subjects with psoriasis have a poor therapeutic response to secukinumab, (3) no data are currently available for secukinumab in PsA obese patients.Objectives:Our studies focused on the relationship between BMI and clinical response to secukinumab in PsA.Methods:We, retrospectively, analysed clinical data of 100 patients with PsA (57% female, median age 53 (49.2-55 years)) satisfying CASPAR criteria (4) for PsA, afferent to our clinic, who were treated with secukinumab. Patients were divided into 2 groups based on BMI (BMI&lt;25 normal weight and BMI≥25 overweight/obese).Results:In the normal weight group 75% were female, median age was 50.5 (41-54.6), median BMI was 22 (20.2-23.3) and median DAPSA was 19.19 (15.6-24.2). The features of the overweight/obese patients were similar to the normal weight group (48% were female, median age 54 (50-59), median BMI 29 (27.4-30.1) and median DAPSA 21.2 (19-24.4)). Clinical response to therapy, evaluated as the achievement of low disease activity or remission according to DAPSA, was recorded 6 months after starting treatment. After 6 months of treatment, the variation of the DAPSA was inversely related to BMI: overweight/obese patients had in fact a better response to secukinumab compared to normal weight patients. By using a correlation coefficient (SPSS), to analyze the degree of association between BMI and DAPSA, we observed that BMI and DAPSA are inversely related in our PsA patients (p=0.05). Interestingly, analysis of serum levels of IL-17 in 20 obese patients compared to 20 non-obese patients, showed significantly higher serum levels of IL-17 in the former (Figure 1), indicating IL-17 as a key cytokine driving inflammation in PsA obese patients.Conclusion:These are the first data about clinical response to secukinumab in obese PsA patients. Our results support the relevance of IL-17 in driving systemic inflammation in obese PsA patients, also providing evidence that obese patients may have a better response to secukinumab compared to non-obese patients. Interestingly, this effect was not

Exposure-Response Relationship of Certolizumab Pegol and Achievement of Low Disease Activity and Remission in Patients With Rheumatoid Arthritis.

Anti‐tumor necrosis factor (anti‐TNF) drugs are often prescribed for the treatment of rheumatoid arthritis (RA) and other immune‐mediated inflammatory diseases. Although this treatment has been shown to be effective in many patients, up to 40% of patients do not achieve disease control. Drug concentration in plasma may be a factor affecting the observed variability in therapeutic response. In this study, we aimed to identify the plasma concentrations of the anti‐TNF certolizumab pegol (CZP), associated with improvement in disease activity in patients with RA. Data were pooled from three randomized, controlled clinical trials with a combined total of 1,935 patients analyzed. Clinical outcomes of low disease activity (LDA) and remission were defined as Disease Activity Score in 28 joints with C‐reactive protein (DAS28(CRP)) ≤ 2.7 and < 2.3, respectively. Quartile analysis results indicated that there may be an exposure‒response relationship between CZP concentration and LDA/remission outcomes at weeks 12 and 24; the association was strongest for LDA (P < 0.05). Receiver operating characteristic (ROC) analysis showed that CZP concentrations ≥ 28.0 μg/ml at week 12, and ≥ 17.6 μg/ml at week 24, were associated with a greater likelihood of achieving LDA/remission outcomes. Although confirmatory studies are warranted to define the optimal CZP therapeutic range at weeks 12 and 24, these data indicate that CZP concentrations may be associated with improvement of disease activity.

The role of targeted synthetic drugs in the treatment of rheumatic diseases: focus on tofacitinib

The treatment of immuno-inflammatory rheumatic diseases has advanced significantly in recent decades due to development of biological medications, which, however, are not without some weak points. They include immunogenicity, parenteral administration, and potentially insufficient stability of the composition of the drug. Great hopes are related to a relatively new class of targeted synthetic immunomodulatory drugs, currently represented in rheumatology by JAK kinase inhibitors (tofacitinib, baricitinib, upadacitinib) and phosphodiesterase 4 inhibitor (apremilast). The most actively developed group is JAK inhibitors that influence one of the most important signal pathway of immune system. This family includes 4 subtypes: JAK1, JAK2, JAK3 и tyrosine-kinase2 (TYK2). JAK-kinases selectively aggregate with cytoplasmic domains of different cytokine receptors, activation of which includes intracellular signal pathway JAK-STAT (Signal Transducer and Activator of Transcription). STAT proteins are responsible for transduction of the signals from more than 50 cytokines, hormones and growth factors that regulate key processes of survival, proliferation and differentiation of immune cells. The greatest practical experience achieved on tofacitinib. This medication approved inRussiafor several indications: rheumatoid arthritis, psoriatic arthritis, psoriasis, ulcerative colitis. Clinical trials of III phase of ORAL series in rheumatoid arthritis and OPAL series in psoriatic arthritis showed high efficacy of Tofacitinib in different clinical situations. In Russian strategic trial REMARKA after treatment with Tofacitinib very fast improvement of the signs of activity was observed, 68,8% patients achieved low disease activity or remission at 6th month of follow-up. Russian open multi-center observational study of Tofacitinib in 101 patients with rheumatoid arthritis and insufficient efficacy of basic and biologic drugs showed achievement of low disease activity or remission in 60% patients, as well as significant improvement of quality of life with a very low frequency of withdrawals due to adverse events (less than 2%).

Outcomes of dose reduction, withdrawal, and restart of tofacitinib in patients with rheumatoid arthritis: a prospective observational study

ObjectiveThis study was designed to compare outcomes of dose reduction, withdrawal, and continuation of tofacitinib in patients with rheumatoid arthritis (RA) and to examine effectiveness of rescue with an original treatment regimen for disease flare.MethodsWe prospectively enrolled 100 patients who had high or moderate disease activity and treated them with tofacitinib at 5 mg twice daily for 1 year. All patients achieving remission or low disease activity (LDA) were assigned to a withdrawal, dose-reduction, or continuation group, then followed until disease flare or end of the study. For flare cases, the original treatment regimen was reintroduced.ResultsDuring the first year, 68 patients achieved remission or LDA (median sustained time 49.0 weeks). Subsequently, disease flare occurred at the following crude incidence rates per person-year (95% confidence interval [CI]): 0.73 (0.43–1.22) after withdrawal, 0.44 (0.25–0.77) after dose reduction, and 0.04 (0.01–0.27) during continuation. Kaplan-Meier estimates of median flare-free time (95% CI) were 7.0 months (2.8–11.2) for withdrawal and 21.0 months (4.1–37.9) for dose reduction. In the Cox regression analysis, adjusted hazard ratios (95% CIs) were 18.11 (2.38–138) for withdrawal and 9.13 (1.19–70.4) for dose reduction compared with continuation. Restart of the original treatment regimen led to rapid remission in flare cases (93% for withdrawal and 100% for dose reduction).ConclusionAfter achievement of remission or LDA, the dose-reduction strategy seems preferable to immediate withdrawal of tofacitinib. Restart of the original regimen can reinduce RA control in flare cases.Key Points• During the 1-year tofacitinib therapy, two-thirds of RA patients with high or moderate disease activity achieved rapid and sustained remission or low disease activity.• During subsequent years, the incidence rate and adjusted hazard ratio for disease flare were significantly higher following tofacitinib immediate withdrawal than following dose reduction.• Half of the patients were estimated to remain flare-free for 21 months after dose reduction and for 7 months after withdrawal of tofacitinib.• Restart of the original treatment regimen rapidly restored disease control in almost all flare cases.

Superiority of a Treat-to-Target Strategy over Conventional Treatment with Fixed csDMARD and Corticosteroids: A Multi-Center Randomized Controlled Trial in RA Patients with an Inadequate Response to Conventional Synthetic DMARDs, and New Therapy with Certolizumab Pegol.

Background: Treatment of rheumatoid arthritis (RA) includes the use of conventional (cs), biologic (b) disease-modifying anti-rheumatic drugs (DMARDs) and oral, intramuscularly, intravenous, or intraarticular (IA) glucocorticoids (GCs). In this paper, we analysed whether a treat-to-target (T2T) strategy optimizing csDMARD, oral, and IA-GC treatment as an adjunct new therapy to a new certolizumab pegol (CZP) therapy improves the effectivity in RA patients. Methods: 43 patients with active RA (≥6 tender, ≥6 swollen joints, ESR ≥ 20 mm/h or CRP ≥ 7mg/L) despite csDMARD treatment for ≥ 3 months and naïve to bDMARDs were randomized to CZP (200 mg/2 weeks after loading with 400 mg at weeks 0–2–4) plus a treat-to-target strategy (T2T, n = 21), or to CZP added to the established csDMARD therapy (fixed regimen, n = 22). The T2T strategy consisted of changing the baseline csDMARD therapy (1) SC-methotrexate (dose: 15 ≥ 20 ≥ 25 mg/week, depending on the initial dose) ≥ leflunomide (20 mg/d) ≥ sulphasalazine (2 × 1000 mg/d) plus (2) oral GCs (prednisolone 20–15–12.5–10–7.5–5–2.5–0 mg/d tapered every five days) and (3) injections of ≤5 affected joints with triamcinolone. DMARD modification and an addition of oral GCs were initiated, depending on the achievement of low disease activity (DAS 28 < 3.2). The primary objective was defined as the ACR 50 response at week 24. Results: ACR 50 was achieved in 76.2% of the T2T, as compared to 36.4% of the fixed regimen patients (p = 0.020). ACR 20 and 70 responses were achieved in 90.5% and 71.4% of the T2T patients and 59.1% and 27.3% of the fixed regimen patients, respectively (p = 0.045 and p = 0.010, respectively). The adverse event rate was similar for both groups (T2T n = 51; fixed regimen n = 55). Conclusion: Treat-to-target management with the optimization of csDMARDs, oral, and IA-GCs of RA patients in parallel to a newly established CZP treatment was safe and efficacious in comparison to a fixed regimen of csDMARDs background therapy.

Use of a multidimensional RAPID3 questionnaire to assess the achievement of remission and minimal disease activity in patients with early psoriatic arthritis treated according to Treat-to-target strategy

The current Treat-to-target (T2T) strategy in the management of patients with psoriatic arthritis (PsA) is based on strict control over the dynamics of a patient's status and timely correction of therapy according to the presence or absence of remission or minimal disease activity (MDA) within 6 months after treatment initiation. The multidimensional RAPID3 questionnaire based on the patient's own opinion of his/her health status, has demonstrated its high effectiveness in assessing remission in patients with rheumatoid arthritis (RA). The possibilities of using the RAPID3 questionnaire in patients with early PsA (ePsA) with T2T strategy have not yet been studied.Objective: to investigate whether the multi-dimensional RAPID3 questionnaire may be used to assess the achievement of remission and MDA in ePsA patients with a T2T (Treat-to-target) strategySubjects and methods. The investigation enrolled 61 patients (29 men and 32 women) with ePsA meeting the 2006 CASPAR criteria; the mean age of the patients was 37±10.6 years; the duration of PsA and psoriasis was 11.3±10.2 and 75.4±80.9 months, respectively. The patients were followed up for 12 months during the open-label REMARCA study performed by the T2T principles. At baseline, all the patients were given methotrexate (MTX; Methoject) subcutaneously at a dose of 10 mg/week, with escalation by 5 mg every 2 weeks up to 20–25 mg/week. If there was no low disease activity (LDA), DAS28/DAS remission, or MDA after 3 months, the patients received combined therapy with MTX 20–25 mg/week and adalimumab (ADA) or ustekinumab (UST) at standard doses. All the patients underwent standard rheumatologic examination before therapy and every 3 months. The investigators calculated tender joint count (TJC) among 78 joints; swollen joint count (SJC) among 76 joints, the Ritchie articular index, and the number of entheses by the Leeds Enthesitis index (LEI). Joint pain measurement, patient (PGA) and physician (PhGA) global assessment on visual analog scale (VAS) was performed, the serum level of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were evaluated. DAS and DAS28, HAQ and RAPID3 functional index were estimated. The number of patients achieving LDA, DAS/DAS28 remission, and MDA were determined. Results and discussion. At 1 year of therapy, 36 (59%) out of the 61 patients and 25 (41%) out of the 61 patients were treated with MTX and this drug in combination with ADA or UST, respectively. After 1 year of treatment, the whole group displayed a significant improvement of all PsA activity parameters as compared with baseline values: DAS, 3.93 [3.20; 4.58] / 1.36 [0.82; 2.25], SJC, 7 [5; 11] / 1 [0; 3], TJC, 8 [6; 1] / 1 [0; 3], PhGA, 56 [48; 69] / 10 [5; 20] and VAS pain, 54 [48; 68] / 11 [1; 20], PGA, 55 [49; 68] / 14 [7; 24], HAQ, 0.75 [0.50; 1] / 0 [0; 0.63], respectively. There was a significant correlation of RAPID3 with PsA activity and CRP. MDA was seen in 43 (70.5%) out of the 61 patients. Among the patients who had achieved MDA, the RAPID3 values corresponded to remission, but were significantly higher in the patients who had not attained MDA: 2.5 [1.3; 5.3] and 8.1 [6.0; 15.1], respectively. RAPID3 demonstrated high sensitivity in assessing the achievement of remission, LDA, and MDA in patients with ePsA.Conclusion. RAPID3 based on a patient's personal opinion of his/her disease is a simple and reliable tool to assess the disease activity in patients with ePsA and to monitor the efficiency of therapy with a T2T strategy and may be really useful in practice.

The three-year efficacy of iguratimod in clinical daily practice in patients with rheumatoid arthritis

Objectives: To assess the middle-term outcome of iguratimod (IGU) in rheumatoid arthritis (RA) patients.Methods: Sixty-nine RA patients (14 males and 55 females, mean age of 64.0 years) receiving IGU-containing therapies were enrolled. We divided these patients into three groups based on the treatment at the baseline: an IGU group, a methotrexate (MTX) plus IGU group, and a biologics plus IGU group. The baseline characteristics and clinical course were evaluated over three years. Predictive factors associated with the achievement of low disease activity (LDA) were statistically analyzed.Results: The survival rate of IGU therapy at 3 years was 40.6%. The disease activity was significantly decreased in the IGU group and MTX plus IGU group compared with the baseline. Furthermore, 38 patients (55.1%) were in remission or had LDA at 3 years. The patient gender, use of prednisolone (PSL) and DAS28-CRP at baseline were the factors associated with the achievement of remission or LDA at three years.Conclusion: IGU was effective without MTX or bDMARDs as well as in combination with MTX. A female gender, no use of PSL and a low DAS28-CRP at the initiation of IGU were associated with clinical remission or LDA achievement at three years.

Real-world Comparative Effectiveness of Tocilizumab Monotherapy vs. Tumor Necrosis Factor Inhibitors with Methotrexate in Patients with Rheumatoid Arthritis.

IntroductionControlled clinical studies have shown that the efficacy of tocilizumab (TCZ) monotherapy is superior to that of tumor necrosis factor inhibitor (TNFi) monotherapy and comparable to that of TCZ plus methotrexate (MTX) for the treatment of rheumatoid arthritis (RA). This study compared the real-world effectiveness of TCZ monotherapy vs. TNFis plus MTX in US patients with RA.MethodsTCZ-naïve patients from the Corrona RA registry with prior exposure to ≥ 1 TNFi who initiated TCZ monotherapy or TNFi + MTX were included. Outcomes included mean change in Clinical Disease Activity Index (CDAI), achievement of low disease activity (LDA; CDAI ≤ 10), achievement of modified American College of Rheumatology (mACR) 20/50 responses, and mean change in modified Health Assessment Questionnaire (mHAQ) at 6 months. Patients initiating TNFi + MTX were grouped by MTX dose (≤ 10 mg; > 10 to ≤ 15 mg; > 15 to ≤ 20 mg; > 20 mg); outcomes in each group were compared with TCZ monotherapy using trimmed populations (excluding patients outside the propensity score distribution overlap).ResultsPatients in all groups experienced improvement in CDAI at 6 months (mean change, − 6.9 to − 9.7), with no significant differences between the TCZ monotherapy and TNFi + MTX groups. Achievement of LDA and mACR responses at 6 months were comparable between the TCZ monotherapy and TNFi + MTX groups; overall, 26.8–38.0% of patients achieved LDA, 24.3–37.6% achieved mACR20 response and 13.2–20.8% achieved mACR50 response. The mean change in mHAQ at 6 months was − 0.1 in all groups.ConclusionsIn this real-world population of US patients with RA who had prior TNFi exposure, there was no evidence of a difference in the effectiveness of TCZ monotherapy compared with that of TNFi + MTX, regardless of MTX dose, at 6 months for improving RA disease activity.FundingCorrona, LLC.Plain Language SummaryPlain language summary available for this article.Electronic supplementary materialThe online version of this article (10.1007/s40744-018-0127-1) contains supplementary material, which is available to authorized users.

Efficacy of infliximab as a switched biologic in rheumatoid arthritis patients in daily clinical practice

To assess the efficacy and safety of switching to infliximab (IFX) from other biological disease-modifying anti-rheumatic drugs (bDMARDs) among Japanese patients with rheumatoid arthritis (RA) in daily practice. We examined 24 consecutive RA patients who had not achieved low disease activity (LDA) as the disease activity score-28 for rheumatoid arthritis with erythrocyte sedimentation rate (DAS28-ESR) despite previous bDMARD therapy in this cohort study. We attempted to determine predictive variables that are associated with achieving DAS28-ESR LDA at 22 weeks post-IFX introduction, by performing univariate analysis. The median DAS28-ESR at baseline was 5.41. Sixteen patients (66.7%) had been treated with a tumor necrosis factor inhibitor (TNF-i), and the other eight patients (33.3%) received a non-TNF-i (abatacept or tocilizumab). Nine patients (37.5%) achieved LDA or remission at 22 weeks. Univariate analyses showed that the variable to predict LDA achievement at 22 weeks was tender joints (>8 counts) at baseline (adjusted odds ratio, 0.10; 95% confidence interval, 0.01–0.63; p = .02). Nine adverse events were observed during the study period, and infection requiring hospitalization was observed in one patient. Switching to IFX is effective to achieve LDA or remission for RA patients refractory to bDMARDs.

Are prognostic factors adequately selected to guide treatment decisions in patients with rheumatoid arthritis? A collaborative analysis from three observational cohorts

ObjectiveTo investigate the impact of indicators of unfavorable prognosis (“poor prognostic factors”) on the achievement of low disease activity (LDA)/remission in patients with rheumatoid arthritis (RA). MethodsBiologic DMARD-naïve patients with RA from three observational cohorts were examined. N = 713 patients started their 1st csDMARD, n = 1613 switched to the 2nd csDMARD and n = 388 to the 1st TNF-inhibitor. High disease activity (DAS28 > 5.1), autoantibodies (RF/ACPA positive), prevalent erosions, functional limitation (HAQ ≥ 1.2), comorbidities, obesity (BMI > 30 kg/m2), and smoking were evaluated as prognostic factors. Generalized regression analyses were applied to investigate prognostic factors regarding the achievement of LDA (DAS28 < 3.2) or remission (DAS28 < 2.6) within six months. ResultsAt baseline, RF/ACPA positivity was most frequent in all cohorts (60.3–75.3%), followed by DAS28 > 5.1 (35–57.7%), HAQ ≥ 1.2 (40.5–52.5%), ≥ 2 comorbidities (31.4–54.1%) and erosions (17.1–46.1%). Remission was achieved by 39% (1st-csDMARD), 26% (2nd-csDMARD) and 30% (1st-TNFi). In adjusted regression models DAS28 > 5.1 (OR: 0.41 [0.30;0.56]), HAQ ≥ 1.2 (0.56 [0.42;0.74]), current smoking (0.72 [0.53;0.97], obesity (0.66 [0.49;0.89] and ≥ 2 comorbidities (0.57 [0.40;0.80]) were independently associated with a lower chance to achieve remission within six months (ORs for 2nd-csDMARD). The proportion of patients in LDA/remission declined by 6–12%-points if DAS28 > 5.1 was present at baseline and by 15–27%-points if functional limitation, comorbidities and obesity were additionally present. In all cohorts RF/ACPA positivity and erosions were not associated with achieving LDA/remission. ConclusionsWhile RF/ACPA status and erosions do not affect the achievement of LDA/remission, high disease activity, functional limitation, comorbidities and obesity should be considered as unfavorable prognostic factors in patients starting the 1st or 2nd DMARD strategy.

Cluster-Randomized Trial of a Behavioral Intervention to Incorporate a Treat-to-Target Approach to Care of US Patients With Rheumatoid Arthritis.

ObjectiveTo assess the feasibility and efficacy of implementing a treat‐to‐target approach versus usual care in a US‐based cohort of rheumatoid arthritis patients.MethodsIn this behavioral intervention trial, rheumatology practices were cluster‐randomized to provide treat‐to‐target care or usual care. Eligible patients with moderate/high disease activity (Clinical Disease Activity Index [CDAI] score >10) were followed for 12 months. Both treat‐to‐target and usual care patients were seen every 3 months. Treat‐to‐target providers were to have monthly visits with treatment acceleration at a minimum of every 3 months in patients with CDAI score >10; additional visits and treatment acceleration were at the discretion of usual care providers and patients. Coprimary end points were feasibility, assessed by rate of treatment acceleration conditional on CDAI score >10, and achievement of low disease activity (LDA; CDAI score ≤10) by an intent‐to‐treat analysis.ResultsA total of 14 practice sites per study arm were included (246 patients receiving treat‐to‐target and 286 receiving usual care). The groups had similar baseline demographic and clinical characteristics. Rates of treatment acceleration (treat‐to‐target 47% versus usual care 50%; odds ratio [OR] 0.92 [95% confidence interval (95% CI) 0.64, 1.34]) and achievement of LDA (treat‐to‐target 57% versus usual care 55%; OR 1.05 [95% CI 0.60, 1.84]) were similar between groups. Treat‐to‐target providers reported patient reluctance and medication lag time as common barriers to treatment acceleration.ConclusionThis study is the first to examine the feasibility and efficacy of a treat‐to‐target approach in typical US rheumatology practice. Treat‐to‐target care was not associated with increased likelihood of treatment acceleration or achievement of LDA, and barriers to treatment acceleration were identified.

Low disease activity for up to 3\xa0years after adalimumab discontinuation in patients with early rheumatoid arthritis: 2-year results of the HOPEFUL-3 Study

BackgroundThis study was conducted to evaluate the feasibility of long-term adalimumab (ADA) discontinuation after achievement of low disease activity (LDA) in Japanese patients with early rheumatoid arthritis (RA) and to identify predictors of LDA maintenance.MethodsIn the HOPEFUL-1 study, patients received initial therapy with either ADA plus methotrexate (MTX; intensive therapy) or MTX alone (standard therapy) for 26 weeks, followed by ADA + MTX for 26 weeks. In the HOPEFUL-2 study, patients received ADA + MTX (ADA continuation) or MTX alone (ADA discontinuation) for 52 weeks. HOPEFUL-3 was an observational study that enrolled patients who had completed HOPEFUL-2; these patients were followed for an additional 104 weeks.ResultsOf the 172 patients enrolled in the HOPEFUL-3 study, 135 (ADA continuation, n = 61; ADA discontinuation, n = 74) with 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP) values at both week 52 (start of HOPEFUL-2) and week 208 (end of HOPEFUL-3) were included in the effectiveness analysis. At week 208, 58 (95.1%) of 61 patients and 59 (79.7%) of 74 patients who continued or discontinued ADA, respectively, had LDA (DAS28-CRP <3.2). Initial intensive therapy was associated with a better outcome than standard therapy in terms of change in modified total Sharp score from week 0 to week 208, which was ≤0.5 (64% vs. 30%). The incidence of adverse events was significantly lower in the ADA discontinuation group than in the ADA continuation group (9.7% vs. 32.9%; p < 0.001).ConclusionsApproximately 80% of patients who discontinued ADA for 3 years after achieving LDA with ADA + MTX were still in LDA, with a lower incidence of adverse events than patients who continued ADA.Trial registrationClinicalTrials.gov identifier: NCT01346501. Registered 29 April 2011.

A window of opportunity for abatacept in RA: is disease duration an independent predictor of low disease activity/remission in clinical practice?

The objective of the study was to examine whether disease duration independently predicts treatment response among biologic-naïve patients with rheumatoid arthritis (RA) initiating abatacept in clinical practice. Using the Corrona RA registry (February 2006–January 2015), biologic-naïve patients with RA initiating abatacept with 12-month (±3 months) follow-up and assessment of disease activity (Clinical Disease Activity Index [CDAI]) at initiation and at 12 months were identified. The primary outcome was mean change in CDAI (ΔCDAI) from baseline to 12 months. Secondary outcomes at 12 months included achievement of low disease activity (LDA; CDAI ≤10 in patients with moderate/high disease activity at initiation) and remission (CDAI ≤2.8 in patients with low, moderate or high disease activity at initiation). Linear and logistic regression analyses were performed to examine the relationship between disease duration and response to abatacept. There were 281 biologic-naïve patients with RA initiating abatacept (disease duration 0–2 years, n = 107; 3–5 years, n = 45; 6–10 years, n = 50; >10 years, n = 79). Increased disease duration was associated with older age (p = 0.047), and the median number of prior conventional disease-modifying antirheumatic drugs used was lowest in the 0- to 2-year duration group (p < 0.001). Mean ΔCDAI (SE) ranged from −10.22 (1.19) for 0–2 years to −4.63 (1.38) for >10 years. In adjusted analyses, shorter disease duration was significantly associated with greater mean ΔCDAI (p = 0.015) and greater likelihood of achieving LDA (p = 0.048). In biologic-naïve patients with RA initiating abatacept, earlier disease (shorter disease duration) was associated with greater ΔCDAI and likelihood of achieving LDA.

Maintenance treatment using abatacept with dose reduction after achievement of low disease activity in patients with rheumatoid arthritis (MATADOR) – A prospective, multicenter, single arm pilot clinical trial

Objectives: To preliminarily evaluate the feasibility of maintenance therapy with reduced dose of intravenous abatacept (ABT) to 250 mg/body/month after achieving remission or low disease activity (LDA).Patients and methods: RA patients treated with ABT at 13 sites were enrolled in this prospective interventional pilot study during the period between March 2013 and March 2015. Inclusion criteria were (1) age at 20 years or older, (2) under treatment with monthly intravenous ABT at approved doses, (3) DAS28-CRP lower than 2.7 at least for 6 months, (4) agreed to join this trial with written informed consent and (5) body weight under 125 kg. Enrolled patients were maintained with intravenous monthly ABT at a reduced dose of 250 mg/body (MATADOR protocol). The primary end point was the proportion of the patients continued with MATADOR protocol at week 48. MATADOR protocol was discontinued upon disease flare or other reasons such as patients’ request or severe adverse event (AE). Disease activities and structural changes were also evaluated.Results: Fifty-three patients fulfilled the entry criteria and were followed for 1-year. MATADOR protocol was continued for 1-year in 43 (81%) of the evaluated patients. Three patients experienced severe AEs. Mean DAS28-CRP and remission rate were 1.56 and 88% when ABT reduced and 1.80 and 81% at 1-year, respectively. Structural remission was achieved in 34 out of 42 evaluated patients.Conclusions: Reduced dose of intravenous ABT was proposed as a feasible choice for maintenance therapy for RA after achievement of remission/LDA, although further randomized trials would be awaited.