AB0208 Prediction of Flare in Rheumatoid Arthritis and Psoriatic Arthritis Patients with Low Disease Activity Receiving Tnf Inhibitors: Role of Calprotectin and Drug Trough Serum Levels. A One-Year Prospective Cohort Study

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

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The sFlt-1 to PlGF Ratio in Pregnant Women with Rheumatoid Arthritis: Impact of Disease Activity and Sulfasalazine Use

Rheumatology ◽

10.1093/rheumatology/keab372 ◽

2021 ◽

Author(s):

Rugina I Neuman ◽

Hieronymus T W Smeele ◽

A H Jan Danser ◽

Radboud J E M Dolhain ◽

Willy Visser

Keyword(s):

Rheumatoid Arthritis ◽

Cohort Study ◽

Disease Activity ◽

Pregnant Women ◽

Gestational Age ◽

Third Trimester ◽

Low Disease Activity ◽

The Third ◽

Observational Prospective Cohort Study ◽

Plgf Ratio

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 > 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.

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POS0647 EFFICACY, SAFETY AND CHARACTERISTICS OF IGURATIMOD-BASED THERAPY IN THE TREATMENT OF UA, ERA AND RA PATIENTS FOR 24 WEEKS: A PROSPECTIVE COHORT STUDY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.91 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 561.2-562

Author(s):

X. Liu ◽

Z. Sun ◽

W. Guo ◽

F. Wang ◽

L. Song ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Cohort Study ◽

Adverse Events ◽

Disease Activity ◽

Prospective Cohort Study ◽

Early Rheumatoid Arthritis ◽

Prospective Cohort ◽

Combined Treatment ◽

Serious Adverse Events

Background:Experts emphasize early diagnosis and treatment in RA, but the widely used diagnostic criterias fail to meet the accurate judgment of early rheumatoid arthritis. In 2012, Professor Zhanguo Li took the lead in establishing ERA “Chinese standard”, and its sensitivity and accuracy have been recognized by peers. However, the optimal first-line treatment of patients (pts) with undifferentiated arthritis (UA), early rheumatoid arthritis (ERA), and rheumatoid arthritis (RA) are yet to be established.Objectives:To evaluate the efficacy and safety of Iguratimod-based (IGU-based) Strategy in the above three types of pts, and to explore the characteristics of the effects of IGU monotherapy and combined treatment.Methods:This prospective cohort study (ClinicalTrials.gov Identifier NCT01548001) was conducted in China. In this phase 4 study pts with RA (ACR 1987 criteria[1]), ERA (not match ACR 1987 criteria[1] but match ACR/EULAR 2010 criteria[2] or 2014 ERA criteria[3]), UA (not match classification criteria for ERA and RA but imaging suggests synovitis) were recruited. We applied different treatments according to the patient’s disease activity at baseline, including IGU monotherapy and combination therapies with methotrexate, hydroxychloroquine, and prednisone. Specifically, pts with LDA and fewer poor prognostic factors were entered the IGU monotherapy group (25 mg bid), and pts with high disease activity were assigned to combination groups. A Chi-square test was applied for comparison. The primary outcomes were the proportion of pts in remission (REM)or low disease activity (LDA) that is DAS28-ESR<2.6 or 3.2 at 24 weeks, as well as the proportion of pts, achieved ACR20, Boolean remission, and good or moderate EULAR response (G+M).Results:A total of 313 pts (26 pts with UA, 59 pts with ERA, and 228 pts with RA) were included in this study. Of these, 227/313 (72.5%) pts completed the 24-week follow-up. The results showed that 115/227 (50.7%), 174/227 (76.7%), 77/227 (33.9%), 179/227 (78.9%) pts achieved DAS28-ESR defined REM and LDA, ACR20, Boolean remission, G+M response, respectively. All parameters continued to decrease in all pts after treatment (Fig 1).Compared with baseline, the three highest decline indexes of disease activity at week 24 were SW28, CDAI, and T28, with an average decline rate of 73.8%, 61.4%, 58.7%, respectively. Results were similar in three cohorts.We performed a stratified analysis of which IGU treatment should be used in different cohorts. The study found that the proportion of pts with UA and ERA who used IGU monotherapy were significantly higher than those in the RA cohort. While the proportion of triple and quadruple combined use of IGU in RA pts was significantly higher than that of ERA and UA at baseline and whole-course (Fig 2).A total of 81/313 (25.8%) pts in this study had adverse events (AE) with no serious adverse events. The main adverse events were infection(25/313, 7.99%), gastrointestinal disorders(13/313, 4.15%), liver dysfunction(12/313, 3.83%) which were lower than 259/2666 (9.71%) in the previous Japanese phase IV study[4].The most common reasons of lost follow-up were: 1) discontinued after remission 25/86 (29.1%); 2) lost 22/86 (25.6%); 3) drug ineffective 19/86 (22.1%).Conclusion:Both IGU-based monotherapy and combined therapies are tolerant and effective for treating UA, ERA, and RA, while the decline in joint symptoms was most significant. Overall, IGU combination treatments were most used in RA pts, while monotherapy was predominant in ERA and UA pts.References:[1]Levin RW, et al. Scand J Rheumatol 1996, 25(5):277-281.[2]Kay J, et al. Rheumatology 2012, 51(Suppl 6):vi5-9.[3]Zhao J, et al. Clin Exp Rheumatol 2014, 32(5):667-673.[4]Mimori T, et al. Mod Rheumatol 2019, 29(2):314-323.Disclosure of Interests:None declared

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