scholarly journals FRI0127 Suppression of radiographic progression after gradual methotrexate tapering in patients with rheumatoid arthritis patients maintaining low disease activity - Prospective multicenter study-

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 645.1-645
Author(s):  
K. Katayama ◽  
K. Yujiro ◽  
T. Okubo ◽  
R. Fukai ◽  
T. Sato ◽  
...  

Background:Many studies have been reported to reduce/discontinue Biologics in the treatment of rheumatoid arthritis (RA). In contrast, study for tapering methotrexate (MTX) has been limited (1,2).Objectives:We prospectively examined whether bone destruction will progress at 48 weeks after tapering or discontinuing MTX (UMIN000028875).Methods:The subjects were RA patients who have maintained low disease activity or lower for 24 weeks or more in DAS28-CRP after MTX administration. Patients having PDUS Grade 2 or 3 per site by bilateral hand ultrasonography (26 area) were excluded in this study owing to risk for joint destruction. The joint destruction was evaluated by the joint X-ray evaluation by modified total Sharp scoring (mTSS) at 1 year after the start of tapering MTX. Evaluation of clinical disease activities, severe adverse events, the continuation rate during MTX tapering were also evaluated. According to tapering response, prognostic factor for good response for tapering, joint destruction was determined. Predictors for successful tapering MTX and progression of bone destruction were determined. Statistical analysis was performed by t-test or Wilcoxon rank sum test using SAS .13.2 software.Results:The subjects were 79 (16 males, 63 females). Age average 60.9 years, disease duration 4 years 4 months, MTX dose 8.43 mg / w, DAS28-CRP 1.52, DMARDs (24.3%), ACPA 192.7 U / ml (70.5%), RF 55.6 IU / ml (65.4%).MTX was tapered from an average of 8.43 mg / w before study to 5.46 mg / w one year later. In the treatment evaluation, DAS28-CRP increased from 1.52 to 1.84. 89.7% of subjects did not progress joint damage. Other disease activities significantly increased (Table 1). The one-year continuation rate was 78.2%. Since tapering effects were varied widely, we divided patients into three groups; Flared group (N=14, initial MTX dose 8.71mg/w, final MTX dose 8.42mg/w), Low response group (N=31, final MTX reduction rate< 50%, initial MTX dose 8.93mg/w, final MTX dose 6.22mg/w), High response group (N=34, final MTX reduction rate≥ 50%, initial MTX dose 8.5mg/w, final MTX dose 3.15mg/w)(Table 2).Higher RF value at baseline and higher MTX dose at 3M, 6M were predictors of whether a subject was in Low response group or High Response group. Higher RF value and mTSS at baseline and higher MTX dose at 6M were predictors whether a subject was in Flared group or High response group. Lower age was predictor of whether a subject was in Flared group or Low responder group. Finally, mean ΔmTSS /y in Flared group (0.36) was not significantly higher than in low response group (0.07) and in high response group (0.01).Table 1Table 2.Predictors for successful tapering MTX and progression of bone destructionConclusion:Patients with MTX-administered low disease activity and finger joint echo PDUS grade 1 satisfy almost no joint destruction even after MTX reduction. For tapering, predictors may be helpful for maintaining patient’s satisfaction.References:[1]Baker KF, Skelton AJ, Lendrem DW et al. Predicting drug-free remission in rheumatoid arthritis: A prospective interventional cohort study. J. Autoimmunity. 2019;105: 102298.[2]Lillegraven S, Sundlisater N, Aga A et al. Tapering of Conventional Synthetic Disease Modifying Anti-Rheumatic Drugs in Rheumatoid Arthritis Patients in Sustained Remission: Results from a Randomized Controlled Trial. American College of Rheumatology. 2019; Abstract L08.Disclosure of Interests:None declared

2016 ◽  
Vol 83 (6) ◽  
pp. 721-725 ◽  
Author(s):  
Florenzo Iannone ◽  
Giorgio Carlino ◽  
Antonio Marchesoni ◽  
Piercarlo Sarzi-Puttini ◽  
Roberto Gorla ◽  
...  

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 98.2-99
Author(s):  
A. De Thurah ◽  
C. Skovsgaard ◽  
T. Maribo ◽  
N. H. Hjøllund ◽  
M. Kruse

Background:The clinical effectiveness of a patient-reported outcome (PRO) based telehealth intervention offered to rheumatoid arthritis (RA) patients with low disease activity or remission has previously been reported1. The TeRA study showed that PRO-based telehealth follow-up in RA achieved similar disease control as conventional outpatient follow-up among patients with low disease activity or remission. The degree of disease control did not differ between telehealth follow-up offered by rheumatologists or rheumatology nurses.Objectives:To compare the cost-effectiveness of PRO–based telehealth follow-up to patients with RA performed by rheumatologists or rheumatology nurses with conventional outpatient follow-up.Methods:A total of 294 patients were randomized (1:1:1) to either PRO-based telehealth follow-up carried out by a nurse (PRO-TN) or a rheumatologist (PRO-TR), or conventional outpatient follow-up by physicians. Quality of life (EQ-5D) was measured at baseline and at follow-up after one year. The primary outcome was a change in the Disease Activity Score, C-reactive Protetin in 28 joints (DAS-28, CRP).The focus in the health economic evaluation was on the relation between costs and EQ-5D in the period between one year prior to and one year after the intervention. All costs were measured at the individual level and consisted of: intervention costs, health and social care costs, and productivity costs. All cost data were retrieved from Danish population-based registers. Incremental cost-effectiveness rates (ICERs) were calculated on the basis of a comparison of the development in costs and effects in the two intervention groups (separately and combined) with the control group. Bootstrap with 10,000 replications were used to access significance.Results:The difference in health and social care costs during the intervention period compared to the year before were €1,072, - €50 and €519 for the control group, the PRO-TR group and the PRO-TN respectively. Hence, the change in health and social care costs was lower for both intervention groups. The PRO-TR group had a small decrease and it was significantly lower than for the control group (p=0.0027). The difference between health and social care costs in the PRO-TN group compared to the control group was only borderline significant (p=0.067). No statistically significant differences were found in QALY’s between the three groups, all three groups experienced minor, non-significant, declines in QALY over the intervention period. ICER’s were not statistically significant but below known threshold values for the PRO-RN group (ICER=€17,121).Conclusion:It is difficult to obtain statistically significant results for cost-effectiveness in small samples. However, the results point towards a possible cost-saving impact of PRO interventions in patients with low disease activity or remission. The study was unable to conclude if PRO-TR or PRO-TN were most cost-effective. Other relevant considerations, like patient satisfaction or organisational issues, should determine the way of organizing RA disease management in these patients.References:[1]de Thurah A, Stengaard-Pedersen K, Axelsen M, et al. Tele-Health Follow-up Strategy for Tight Control of Disease Activity in Rheumatoid Arthritis: Results of a Randomized Controlled Trial.Arthritis care & research2018;70(3): 353-60.Disclosure of Interests:Annette de Thurah Grant/research support from: Novartis (not relevant for the present study)., Speakers bureau: Lily (not relevant for the present study)., Christian Skovsgaard: None declared, Thomas Maribo: None declared, Niels Henrik Hjøllund: None declared, Marie Kruse: None declared


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 552.1-552
Author(s):  
J. W. Park ◽  
M. J. Kim ◽  
H. A. Kim ◽  
J. Kim ◽  
E. B. Lee ◽  
...  

Background:Tapering biologic therapy after achieving clinical remission or low disease activity (LDA) has become a viable option in daily clinical practice of treating patients with rheumatoid arthritis (RA). There are yet few studies investigating its effectiveness and safety compared with those of standard biologic treatment, especially with non-tumor necrosis factor inhibitors.Objectives:To investigate the effectiveness and safety of tapering tocilizumab (TCZ) in patients with RA who attained LDA after TCZ therapy.Methods:Data were collected from a nationwide cohort of patients with RA receiving biologic therapy in South Korea (KOBIO-RA). This study included 350 patients who were treated with TCZ and achieved Clinical Disease Activity Index (CDAI)-LDA or remission (CDAI ≤ 10) after one year of treatment. We performed a longitudinal analysis utilizing clinical data measured in all 1-year intervals using generalized estimating equations (GEE). A total of 575 one-year intervals were divided into two groups according to the dose quotient (DQ, 0-100%) of TCZ within the interval (tapering group vs. standard treatment group). The main outcome of this study was loss of CDAI-LDA in the following 1-year interval.Results:Tapering TCZ was conducted in 282 (49.0%) intervals with a mean (SD) DQ of 66.0 (15.5). Loss of CDAI-LDA occurred in 91 (15.1%) intervals. Multivariable GEE showed significantly increased loss of CDAI-LDA (adjusted OR (95% CI): 1.76 [1.01 to 3.07]) in the tapering group after adjusting for previous biologics use, route of TCZ administration, concomitant glucocorticoid use, and CDAI measured in the previous follow-up. In addition, the likelihood to achieve DAS28-deep remission (DAS28-ESR < 1.98) was also significantly lower in the tapering group (adjusted OR 0.68 [0.46 to 0.99]). In contrast, there was no significant difference in the proportion of fulfilling other remission criteria between the two groups (Table 1). Development any adverse drug event or event of special interest was comparable in both groups except for hypercholesterolemia, which was lower in the tapering group.Table 1.Demographic characteristics and csDMARDs before first bDMARDLoss of CDAI-LDADAS28-remissionDAS28-deep remissionCDAI-remissionSDAI-remissionACR/EULAR remissionUnadjusted OR (95% CI)(vs. standard-dose group)1.02 (0.67 to 1.55)1.03 (0.71 to 1.49)0.76 (0.54 to 1.06)1.23 (0.75 to 2.00)0.92 (0.59 to 1.44)0.98 (0.65 to 1.48)Adjusted OR(95% CI)(vs. standard-dose group)1.76 (1.01 to 3.07)0.87 (0.54 to 1.38)0.68 (0.46 to 0.99)0.94 (0.57 to 1.55)0.87 (0.54 to 1.38)0.76 (0.50 to 1.18)CDAI, clinical disease activity index; CI, confidence interval; DAS, disease activity score; LDA, low disease activity; OR, odds ratio; SDAI, simplified disease activity index.Conclusion:Tapering TCZ after achieving LDA in patients with RA increases the risk of losing the benefit of LDA without a significant merit in safety.References:[1]Smolen JS et al. Maintenance, reduction or withdrawal of etanercept after treatment with etanercept and methotrexate in patients with moderate rheumatoid arthritis (PRESERVE): a randomised controlled trial. Lancet. 2013;381:918-29.[2]Schett G et al. Tapering biologic and conventional DMARD therapy in rheumatoid arthritis: current evidence and future directions. Ann Rheum Dis. 2016;75:1428-37.Disclosure of Interests:None declared


2018 ◽  
Vol 86 (September) ◽  
pp. 3341-3348
Author(s):  
DALIA B. EL-BOHOTY, M.Sc.; DOAA S. AL-ASHKAR, M.D. ◽  
MAALY M. MABROUK, M.D.; HALA M. NAGY, M.D.

2016 ◽  
Vol 75 (Suppl 2) ◽  
pp. 454.1-454
Author(s):  
G. Akdemir ◽  
I.M. Markusse ◽  
A.A. Schouffoer ◽  
P.B. de Sonnaville ◽  
B.A. Grillet ◽  
...  

Rheumatology ◽  
2021 ◽  
Author(s):  
Rugina I Neuman ◽  
Hieronymus T W Smeele ◽  
A H Jan Danser ◽  
Radboud J E M Dolhain ◽  
Willy Visser

Abstract Objectives An elevated sFlt-1/PlGF-ratio has been validated as a significant predictor of preeclampsia, but has not been established in women with rheumatoid arthritis (RA). We explored whether the sFlt-1/PlGF-ratio could be altered due to disease activity in RA, and could be applied in this population to predict preeclampsia. Since sulfasalazine has been suggested to improve the angiogenic imbalance in preeclampsia, we also aimed to examine whether sulfasalazine could affect sFlt-1 or PlGF levels. Methods Making use of a nationwide, observational, prospective cohort study on pregnant women with RA, sFlt-1 and PlGF were measured in the third trimester. A total of 221 women, aged 21–42 years, were included, with a median gestational age of 30 + 3 weeks. Results No differences in sFlt-1 or PlGF were observed between women with high, intermediate or low disease activity (p= 0.07 and p= 0.41), whereas sFlt-1 and PlGF did not correlate with DAS28-CRP score (r=-0.01 and r=-0.05, respectively). Four (2%) women with a sFlt-1/PlGF-ratio ≤38 developed preeclampsia in comparison to three (43%) women with a ratio &gt; 38, corresponding to a negative predictive value of 98.1%. Sulfasalazine users (n = 57) did not show altered levels of sFlt-1 or PlGF in comparison to non-sulfasalazine users (n = 164, p= 0.91 and p= 0.11). Conclusion Our study shows that in pregnant women with RA, the sFlt-1/PlGF-ratio is not altered due to disease activity and a cut-off ≤38 can be used to exclude preeclampsia. Additionally, sulfasalazine use did not affect sFlt-1 or PlGF levels in this population.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1463.2-1464
Author(s):  
S. Bayat ◽  
K. Tascilar ◽  
V. Kaufmann ◽  
A. Kleyer ◽  
D. Simon ◽  
...  

Background:Recent developments of targeted treatments such as targeted synthetic DMARDs (tsDMARDs) increase the chances of a sustained low disease activity (LDA) or remission state for patients suffering rheumatoid arthritis (RA). tsDMARDs such as baricitinib, an oral inhibitor of the Janus Kinases (JAK1/JAK2) was recently approved for the treatment of RA with an inadequate response to conventional (cDMARD) and biological (bDMARD) therapy. (1, 2).Objectives:Aim of this study is to analyze the effect of baricitinb on disease activity (DAS28, LDA) in patients with RA in real life, to analyze drug persistance and associate these effects with various baseline characteristics.Methods:All RA patients were seen in our outpatient clinic. If a patient was switched to a baricitinib due to medical reasons, these patients were included in our prospective, observational study which started in April 2017. Clinical scores (SJC/TJC 76/78), composite scores (DAS28), PROs (HAQ-DI; RAID; FACIT), safety parameters (not reported in this abstract) as well as laboratory biomarkers were collected at each visit every three months. Linear mixed effects models for repeated measurements were used to analyze the time course of disease activity, patient reported outcomes and laboratory results. We estimated the probabilities of continued baricitinib treatment and the probabilities of LDA and remission by DAS-28 as well as Boolean remission up to one year using survival analysis and explored their association with disease characteristics using multivariable Cox regression. All patients gave informed consent. The study is approved by the local ethics.Results:95 patients were included and 85 analyzed with available follow-up data until November 2019. Demographics are shown in table 1. Mean follow-up duration after starting baricitinib was 49.3 (28.9) weeks. 51 patients (60%) were on monotherapy. Baricitinib survival (95%CI) was 82% (73% to 91%) at one year. Cumulative number (%probability, 95%CI) of patients that attained DAS-28 LDA at least once up to one year was 67 (92%, 80% to 97%) and the number of patients attaining DAS-28 and Boolean remission were 31 (50%, 34% to 61%) and 12(20%, 9% to 30%) respectively. Median time to DAS-28 LDA was 16 weeks (Figure 1). Cox regression analyses did not show any sufficiently precise association of remission or LDA with age, gender, seropositivity, disease duration, concomitant DMARD use and number of previous bDMARDs. Increasing number of previous bDMARDs was associated with poor baricitinib survival (HR=1.5, 95%CI 1.1 to 2.2) while this association was not robust to adjustment for baseline disease activity. Favorable changes were observed in tender and swollen joint counts, pain-VAS, patient and physician disease assessment scores, RAID, FACIT and the acute phase response.Conclusion:In this prospective observational study, we observed high rates of LDA and DAS-28 remission and significant improvements in disease activity and patient reported outcome measurements over time.References:[1]Keystone EC, Taylor PC, Drescher E, Schlichting DE, Beattie SD, Berclaz PY, et al. Safety and efficacy of baricitinib at 24 weeks in patients with rheumatoid arthritis who have had an inadequate response to methotrexate. Annals of the rheumatic diseases. 2015 Feb;74(2):333-40.[2]Genovese MC, Kremer J, Zamani O, Ludivico C, Krogulec M, Xie L, et al. Baricitinib in Patients with Refractory Rheumatoid Arthritis. The New England journal of medicine. 2016 Mar 31;374(13):1243-52.Figure 1.Cumulative probability of low disease activity or remission under treatment with baricitinib.Disclosure of Interests:Sara Bayat Speakers bureau: Novartis, Koray Tascilar: None declared, Veronica Kaufmann: None declared, Arnd Kleyer Consultant of: Lilly, Gilead, Novartis,Abbvie, Speakers bureau: Novartis, Lilly, David Simon Grant/research support from: Else Kröner-Memorial Scholarship, Novartis, Consultant of: Novartis, Lilly, Johannes Knitza Grant/research support from: Research Grant: Novartis, Fabian Hartmann: None declared, Susanne Adam: None declared, Axel Hueber Grant/research support from: Novartis, Lilly, Pfizer, EIT Health, EU-IMI, DFG, Universität Erlangen (EFI), Consultant of: Abbvie, BMS, Celgene, Gilead, GSK, Lilly, Novartis, Speakers bureau: GSK, Lilly, Novartis, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB


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