Disease activity guided stepwise tapering or discontinuation of rhTNFR:Fc, an etanercept biosimilar, in patients with ankylosing spondylitis: a prospective, randomized, open-label, multicentric study

Background: The aim of this study was to evaluate disease-activity-guided stepwise tapering or discontinuation of rhTNFR:Fc, an etanercept biosimilar, in patients with ankylosing spondylitis (AS) in a prospective, randomized, open-label, multicentric study. Methods: Active AS patients with AS disease activity score (ASDAS) ⩾2.1 recruited from 10 hospitals were treated with rhTNFR:Fc 50 mg weekly for 12 weeks, and further randomized into different tapering or discontinuation groups according to ASDAS at week 12. Patients who achieved clinical remission (ASDAS < 1.3) were assigned randomly to stepwise tapering group or discontinuation group. Patients who achieved low disease activity (LDA, 1.3⩽ASDAS < 2.1) were assigned randomly to stepwise tapering, delayed tapering, or discontinuation group. All patients were evaluated every 12 weeks until week 48. The primary endpoint was cumulative flare rates in different groups at week 48. Results: A total of 311 patients were enrolled with an average ASDAS of 3.6 ± 1.0, and 259 completed 12 weeks of rhTNFR:Fc induction therapy, with 148 patients (57.1%) achieved clinical remission, 100 (38.6%) achieved LDA, and 11 (4.3%) remained as high disease activity (ASDAS⩾2.1). In patients who achieved clinical remission at week 12, stepwise tapering of rhTNFR:Fc demonstrated significantly lower flare rates at each evaluation compared with discontinuation. In patients who achieved LDA, there was no significant difference of flare rates between stepwise tapering, delayed tapering, and discontinuation. With stepwise tapering of rhTNFR:Fc, flare rates were comparable in AS patients, irrespective of initial ASDAS before tapering. Conclusion: Stepwise tapering of rhTNFR:Fc when patients achieved clinical remission was able to maintain favorable low flare rates in 48 weeks. LDA was an alternative therapeutic target, as well as an viable timing for initiation of rhTNFR:Fc tapering. rhTNFR:Fc 25 mg monthly maintained flare-free status in a considerable number of patients. However, abrupt discontinuation of rhTNFR:Fc even if patients achieved clinical remission should be avoided. Trial registration: ClinicalTrials.gov: NCT03880968, URL: https://clinicaltrials.gov/ct2/show/NCT03880968

Download Full-text

Sustained Clinical Remission and Rate of Relapse After Tocilizumab Withdrawal in Patients with Rheumatoid Arthritis

The Journal of Rheumatology ◽

10.3899/jrheum.121427 ◽

2013 ◽

Vol 40 (7) ◽

pp. 1069-1073 ◽

Cited By ~ 31

Author(s):

Luis Aguilar-Lozano ◽

Jose Dionisio Castillo-Ortiz ◽

Cesar Vargas-Serafin ◽

Jorge Morales-Torres ◽

Adriana Sanchez-Ortiz ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Clinical Remission ◽

Disease Activity Score ◽

Additional Data ◽

Clinical Relapse ◽

Antiinflammatory Drugs ◽

Open Label ◽

Low Disease Activity ◽

Number Of Patients

Objective.Data on when to stop use of biological agents in rheumatoid arthritis (RA) are scant. We assessed the length of remission and the rate of clinical relapse in patients with RA who had to discontinue treatment with tocilizumab (TCZ) because of the ending of longterm (5 yrs) open-label clinical trials.Methods.All patients at 2 participating centers in Mexico were in remission, defined as Disease Activity Score 28 ≤ 2.6, with no swollen joints at the time of the last TCZ infusion. Patients were followed thereafter every 8 weeks for 12 months or until relapse. Relapse was defined as the presence of ≥ 1 swollen joint. Doses of methotrexate and antiinflammatory drugs were not changed during the followup period.Results.Forty-five patients were analyzed, 87% were women (mean age 52 yrs, mean disease duration 14 yrs). During the 12 months of followup, 44% of patients maintained remission. Relapses occurred in 56% of patients: 14 during the first 3 months after the last TCZ administration. Retreatment using other agents achieved low disease activity or remission.Conclusion.Longterm clinical remission is possible in a number of patients with RA after suspension of TCZ. This effect has also been reported with other biologic agents. Additional data are required to support recommendations for discontinuing a biological agent after achieving remission.

Download Full-text

Prolonged clinical remission and low disease activity statuses are associated with better quality of life in systemic lupus erythematosus

Lupus ◽

10.1177/0961203319862614 ◽

2019 ◽

Vol 28 (10) ◽

pp. 1189-1196 ◽

Cited By ~ 5

Author(s):

N Poomsalood ◽

P Narongroeknawin ◽

S Chaiamnuay ◽

P Asavatanabodee ◽

R Pakchotanon

Keyword(s):

Quality Of Life ◽

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Clinical Remission ◽

Life Questionnaire ◽

Systemic Lupus ◽

Low Disease Activity ◽

Significant Difference

Objective The objective of this study was to determine the association between disease activity status and health-related quality of life (HRQoL) in systemic lupus erythematosus (SLE) patients. Methods SLE patients in an out-patient clinic during the previous 12 months were included in the study. The Systemic Lupus Erythematosus-specific Quality-of-Life questionnaire (SLEQoL) was administered at the last visit. Disease activity status was determined retrospectively during the previous year. The categories of disease activity status were defined as: clinical remission (CR): clinical quiescent disease according to Systemic Lupus Erythematosus Disease Activity Index 2000, prednisolone ≤ 5 mg/day; low disease activity (LDA): SLEDAI-2K (without serological domain) ≤ 2, prednisolone ≤ 7.5 mg/day; and non-optimally controlled status: for those who were not in CR/LDA. Immunosuppressive drugs (maintenance dose) and antimalarials were allowed. Prolonged CR or LDA was defined as those with sustained CR or LDA for at least one year. The association between disease activity status and HRQoL was assessed by using regression analysis adjusting for other covariates. Results Of 237 SLE patients, 100 patients (42.2%) achieved prolonged CR, 46 patients (19.4%) achieved prolonged LDA and 91 patients (38.4%) were not in CR/LDA. Non-CR/LDA patients had significantly higher total SLEQoL score and in all domains compared to CR/LDA patients. No significant difference in SLEQoL domain scores was found between CR and LDA groups. Multivariable analysis revealed that non-CR/LDA was positively associated with SLEQoL score compared with CR/LDA (β 20.02, 95% confidence interval (CI) 6.81–33.23, p < 0.003). Moreover, non-CR/LDA was at a higher risk of impaired QoL (SLEQoL score > 80) compared with CR (hazard ratio 3.8; 95% CI 1.82–7.95; p < 0.001). However, there was no significant difference between CR and LDA in terms of SLEQoL score or impaired QoL. Other factors associated with higher SLEQoL score were damage index (β 9.51, 95% CI 3.52–15.49, p = 0.002) and anemia (β 24.99, 95% CI 5.71–44.27, p = 0.01). Conclusion Prolonged CR and LDA are associated with better HRQoL in SLE patients and have a comparable effect. Prolonged CR or optional LDA may be used as the treatment goal of a treat to target approach in SLE.

Download Full-text

Pregnancy outcomes between pregnant systemic lupus erythematosus patients with clinical remission and those with low disease activity: A comparative study

Archives of Rheumatology ◽

10.46497/archrheumatol.2022.9140 ◽

2021 ◽

Author(s):

Worawit Louthrenoo ◽

Thananant Trongkamolthum ◽

Nuntana Kasitanon ◽

Antika Wongthanee

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Pregnancy Outcomes ◽

Clinical Remission ◽

Activity Index ◽

Physician Global Assessment ◽

Systemic Lupus ◽

Low Disease Activity ◽

Significant Difference

Objectives: This study aims to compare pregnancy outcomes between systemic lupus erythematosus (SLE) patients who attained clinical remission based on the Definition of Remission in SLE (DORIS) and those with lupus low disease activity based on Low Lupus Disease Activity State (LLDAS). Patients and methods: Between January 1993 and June 2017, a total of 90 pregnancies (one twin pregnancy) from 77 patients (mean age: 6.9±4.8 years; range, 17.9 to 37.3 years) were included in the study. The clinical remission and the LLDAS groups were modified into modified clinical remission and LLDAS groups, respectively by omitting Physician Global Assessment (PGA). The clinical SLE disease activity index (cSLEDAI) score was used for LLDAS. Results: Pregnancies in 49 patients occurred, when they were in modified clinical remission and in 57 in modified LLDAS. There was no significant difference in demographic characteristics, disease activity, or medication received at conception between the two groups. Pregnancy outcomes were similar between the modified clinical remission and the modified LLDAS groups in terms of successful pregnancy (83.67% vs. 84.21%), full-term births (38.78% vs. 38.60%), fetal losses (16.33% vs. 15.79%), spontaneous abortions (14.29% vs. 14.04%), small for gestational age infants (18.37% vs. 19.30%), low birth weight infants (42.86% vs. 40.35%), maternal complications (46.94% vs. 49.12%), and maternal flares (36.73% vs. 40.35%). The agreement of pregnancy outcomes was very high between the two groups (91.11% agreement). Conclusion: Pregnancy outcomes in SLE patients who achieved modified clinical remission and modified LLDAS were comparable.

Download Full-text

Maintained Clinical Remission in Ankylosing Spondylitis Patients Switched from Reference Infliximab to Its Biosimilar: An 18-Month Comparative Open-Label Study

Journal of Clinical Medicine ◽

10.3390/jcm8070956 ◽

2019 ◽

Vol 8 (7) ◽

pp. 956 ◽

Cited By ~ 3

Author(s):

Kaltsonoudis Evripidis ◽

Pelechas Eleftherios ◽

Voulgari V. Paraskevi ◽

Drosos A. Alexandros

Keyword(s):

Ankylosing Spondylitis ◽

Disease Activity ◽

Clinical Remission ◽

Activity Index ◽

Disease Activity Index ◽

Control Group ◽

Nocebo Effect ◽

Open Label

Background: Switching from reference infliximab (RI) to biosimilar infliximab (BI) had no detrimental effects on efficacy and safety. However, long-term follow-up data is missing. Objective: To evaluate patients with Ankylosing Spondylitis (AS) in clinical remission who were switching from RI to BI, in terms of the safety and efficacy of this, in a long-term fashion. Methods: One hundred and nine consecutive unselected AS patients were investigated. All were naïve to other biologics and were followed-up at predefined times receiving RI. Patients in clinical remission were asked to switch from RI to BI. Those who switched to BI were compared with a matched control-group receiving continuous RI. During follow-up, several parameters were recorded for at least 18 months. Disease activity was measured using the Bath Ankylosing Spondylitis disease activity index (BASDAI), and the Ankylosing Spondylitis disease activity score (ASDAS), using the C-reactive protein. Remission was defined as BASDAI < 4 and ASDAS < 1.3. Results: Eighty-eight patients were evaluated (21 excluded for different reasons). From those, 45 switched to BI, while 43 continued receiving RI. No differences between groups regarding demographic, clinical and laboratory parameters were observed. All patients were in clinical remission. During follow-up, five patients from the BI-group and three from the maintenance-group discontinued the study (4 patients nocebo effect, 1 loss of efficacy). After 18 months of treatment, all patients in both groups remained in clinical remission. No significant adverse events were noted between groups. Conclusion: BI is equivalent to RI in maintaining AS in clinical remission for at least 18 months.

Download Full-text

EFFICACY AND SAFETY OF TOFACITINIB IN PATIENTS WITH PSORIATIC ARTHRITIS IN REAL CLINICAL PRACTICE

Rheumatology Science and Practice ◽

10.14412/1995-4484-2020-268-275 ◽

2020 ◽

Vol 58 (3) ◽

pp. 268-275

Author(s):

E. Yu. Loginova ◽

Yu. L. Korsakova ◽

E. E. Gubar ◽

P. L. Karpova ◽

T. V. Korotaeva

Keyword(s):

Psoriatic Arthritis ◽

Ankylosing Spondylitis ◽

Disease Activity ◽

Disease Activity Score ◽

Clinical Manifestations ◽

Activity Score ◽

Tender Joint Count ◽

Efficacy And Safety ◽

Low Disease Activity ◽

Number Of Patients

Objective: to evaluate the clinical efficacy and safety of the targeted synthetic disease-modifying anti-rheumatic drug (DMARD) tofacitinib (TOFA; Yakvinus®) in patients with active psoriatic arthritis (PsA) at 12 and 24 weeks after starting treatment. To define the place of TOFA in the therapy of PsA patients. Subjects and methods. Examinations were made in 41 patients (17 men and 24 women) with active PsA and an insufficient response to previous treatment with synthetic DMARDs and/or biological agents (BA). Before starting therapy, the median disease activity for psoriatic arthritis (DAPSA) and disease activity score (DAS28) were 44.2 [37.8; 55.3] and 5.5 [4.7; 6.1], respectively. TOFA tablets were prescribed at a dose of 5 mg twice daily for 24 weeks with possible dose escalation to 10 mg twice daily after 12 weeks. At the beginning of the investigation, at 12 and 24 weeks, the investigators assessed disease activity and TOFA therapy efficiency of according to DAPSA, DAS28 and minimal disease activity (MDA) criteria: tender joint count ≤1, swollen joint count ≤1, a psoriasis area severity index (PASI) ≤1 or body surface area (BSA) ≤3%, pain intensity ≤15 mm, patient global assessment ≤20 mm, Health Assessment Questionnaire (HAQ) ≤0.5, and enthesitis ≤1. They also determined the number of patients who had achieved remission (DAPSA ≤4, DAS28 score <2.6), low disease activity (DAPSA 5-14, ≤2.6, DAS28 <3.2) or MDA (5 out of the 7 criteria) during TOFA therapy at 24-week follow-up. The safety of therapy was evaluated by analyzing the drug-induced adverse events (AE): the frequency, severity and time of their occurrence were studied. Results and discussion. At 24 weeks after initiation of TOFA therapy, there was a significant decrease of median DAPSA and DAS28 values as compared to baseline, to 11 [4.3; 17.3] and 2.6 [1.7; 3.4] respectively. The median Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) also significantly decreased from 6 [4.2; 7] and 3.8 [2.8; 4.4] to 1.4 [0.6; 3.2] and 1.5 [1; 2.1] respectively. The median BSA was significantly reduced from 3 [1; 5] to 0.5 [0.1; 2]. At 24 weeks after initiation of TOFA therapy, DAPSA and DAS28 low disease activity/remission were achieved by 38.5/23.1% and 17.9/53.9% of patients, respectively. Fifteen (38.5%) patients achieved MDA. 38 (92.7%) of the 41 patients completed a full TOFA therapy cycle. Two patients dropped out of the investigation due to ineffective therapy and one due to AE (diarrhea occurring up to 10 times daily, headache, elevated blood pressure, and lacrimation). At 24 weeks, 14 (34.2%) patients reported to have AE. The most common AE noted in 7 (17.1%) patients were infections: acute respiratory viral infection (n=3), fever (n=2), and folliculitis (n=2). In addition, two patients had diarrhea and two had headache. Conclusion. TOFA is an effective drug for the treatment of PsA patients with moderate or high inflammatory activity, has a significant effect on all clinical manifestations of PsA and has a satisfactory safety profile.

Download Full-text

POS0369 ELEVATED EXPRESSION OF TIM-3 ON NEUTROPHILS CORRELATES WITH DISEASE ACTIVITY AND SEVERITY OF ANKYLOSING SPONDYLITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3516 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 414.2-415

Author(s):

X. Huang ◽

T. W. Li ◽

J. Chen ◽

Z. Huang ◽

S. Chen ◽

...

Keyword(s):

Flow Cytometry ◽

Ankylosing Spondylitis ◽

Disease Activity ◽

Immune Cells ◽

Clinical Manifestations ◽

Innate Immune ◽

Innate Immune Cells ◽

Bacterial Killing ◽

Markers Of Inflammation ◽

Significant Difference

Background:Ankylosing spondylitis (AS) is a type of common, chronic inflammatory disease that compromises the axial skeleton and sacroiliac joints, causing inflammatory low back pain and progressive spinal stiffness, over time some patients develop spinal immobility and ankylosis which can lead to a decrease in quality of life. The last few decades, evidence has clearly indicated that neutrophil also plays key roles in the progression of AS. However, the immunomodulatory roles and mechanisms of neutrophils in AS are poorly understood. T-cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) has been reported as an important regulatory molecule, expressed and regulated on different innate immune cells, plays a pivotal role in several autoimmunity diseases. Recent study indicates that Tim3 is also expressed on neutrophils. However, the frequency and roles of Tim3-expressing neutrophils in AS was not clear.Objectives:In this study, we investigated the expression of Tim3 on neutrophils in AS patients and explored the correlation between the level of Tim3-expressing neutrophils and the disease activity and severity of AS.Methods:Patients with AS were recruited from Guangdong Second Provincial General Hospital (n=62). Age/sex-matched volunteers as Healthy controls (HC) (n=39). The medical history, clinical manifestations, physical examination, laboratory measurements were recorded. The expression of costimulatory molecules including programmed death 1 (PD-1), Tim-3 on neutrophils were determined by flow cytometry. The mRNA expression of PD-1 and Tim-3 was determined by real-time PCR. The levels of Tim3-expressing neutrophils in AS patients were further analyzed for their correlation with the markers of inflammation such as ESR,CRP,WBC and neutrophil count(NE), as well as disease activity and severity of AS. The expression of Tim3 on neutrophils was monitored during the course of treatment (4 weeks).Results:The expression of Tim3 on neutrophils in patients with AS was increased compared to the HC (Figure 1A). However, significant difference was observed in the frequency of PD-1-expressing neutrophils between AS patients and HC (Figure 1B). The expression analysis of Tim-3 mRNA, but not PD-1, confirmed the results obtained from flow cytometry (Figure 1C). The level of Tim3-expressing neutrophils in patients with AS showed an positive correlation with ESR, CRP and ASAS-endorsed disease activity score (ASDAS) (Figure 1D). Moreover, the frequency of Tim3-expressing neutrophils in active patients(ASDAS≥1.3) was increased as compare with the inactive patients (ASDAS<1.3) (Figure 1E). As shown in Figure 1F, the frequency of Tim3-expressing neutrophils decreased after the treatment.Conclusion:Increased Tim-3 expression on neutrophils may be a novel indicator to assess disease activity and severity in AS, which may serves as a negative feedback mechanism preventing potential tissue damage caused by excessive inflammatory responses in AS patients.References:[1]Han, G., Chen, G., Shen, B. & Li, Y., Tim-3: an activation marker and activation limiter of innate immune cells. FRONT IMMUNOL 4 449 (2013).[2]Vega-Carrascal, I. et al., Galectin-9 signaling through TIM-3 is involved in neutrophil-mediated Gram-negative bacterial killing: an effect abrogated within the cystic fibrosis lung. J IMMUNOL 192 2418 (2014).Figure 1.(A,B)The expression of Tim3 and PD-1 on neutrophils in AS and HC were determined by flow cytometry.(C) The expression of Tim3 and PD-1 on neutrophils in AS and HC were determined by RT-PCR.(D)The correction between Tim3-expressing neutrophils and ESR,CRP,ASDAS.(E) The expression of Tim3 on neutrophils in active and inactive patients.(F) Influence of treatment on the frequency of Tim3-expressing neutrophils.Disclosure of Interests:None declared

Download Full-text

OP0008 DEVELOPMENT AND VALIDATION OF AN ALTERNATIVE ANKYLOSING SPONDYLITIS DISEASE ACTIVITY SCORE WHEN PATIENT GLOBAL ASSESSMENT IS UNAVAILABLE

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.1122 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 6-6

Author(s):

A. Ortolan ◽

S. Ramiro ◽

F. A. Van Gaalen ◽

T. K. Kvien ◽

R. B. M. Landewé ◽

...

Keyword(s):

Ankylosing Spondylitis ◽

Disease Activity ◽

Psychometric Properties ◽

Global Assessment ◽

Disease Activity Score ◽

Validation Cohort ◽

Patient Global Assessment ◽

Activity Score ◽

Research Support ◽

Low Disease Activity

Background:Ankylosing Spondylitis Disease Activity Score (ASDAS) is a composite index measuring disease activity in axial spondyloarthritis (axSpA). It includes questions from the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Patient Global Assessment (PGA), and inflammation biomarkers. However, ASDAS calculation is not always possible because PGA is sometimes not collected.Objectives:To develop an alternative ASDAS to be used in research settings when PGA is unavailable.Methods:Longitudinal data from 4 axSpA cohorts and 2 RCTs were combined. Observations were randomly split in a development (N=1026) and a validation cohort (N=1059). Substitutes of PGA by BASDAI total score, single or combined individual BASDAI questions, and a constant value, were considered. In the development cohort, conversion factors for each substitute were defined by Generalized Estimating Equations. Validation was performed in the validation cohort according to the OMERACT filter, taking into consideration: 1) Truth (agreement with original-ASDAS in the continuous score, by intraclass correlation coefficient -ICC- and in disease activity states, by weighted kappa) 2) Discrimination (standardized mean difference –SMD- of ASDAS scores between high/low disease activity states defined by external anchors e.g Patient Acceptable Symptom State –PASS-; agreement -kappa- in the % of patients reaching ASDAS improvement criteria according to alternative vs. original formulae) 3) Feasibility.Results:Taking all psychometric properties into account and comparing the different formulae (Table), alternative-ASDAS using BASDAI total as PGA replacement proved to be: 1) truthful (agreement with original-ASDAS: ICC=0.98, kappa=0.90); 2) discriminative: it could discriminate between high/low disease activity states (e.g. scores between PASS no/yes: SMD=1.37 versus original-ASDAS SMD=1.43) and was sensitive to change (agreement with original-ASDAS in major improvement/clinically important improvement criteria: kappa=0.93/0.88; 3) feasible (BASDAI total often available; conversion coefficient≈1).Table.Psychometric properties of alternative ASDAS formulaeConclusion:Alternative-ASDAS using BASDAI total score as PGA replacement is the most truthful, discriminative and feasible instrument. This index enables ASDAS calculation in existing cohorts without PGA.Disclosure of Interests:Augusta Ortolan: None declared, Sofia Ramiro: None declared, Floris A. van Gaalen: None declared, Tore K. Kvien Grant/research support from: Received grants from Abbvie, Hospira/Pfizer, MSD and Roche (not relevant for this abstract)., Consultant of: Have received personal fees from Abbvie, Biogen, BMS, Celltrion, Eli Lily, Hospira/Pfizer, MSD, Novartis, Orion Pharma, Roche, Sandoz, UCB, Sanofi and Mylan (not relevant for this abstract)., Paid instructor for: Have received personal fees from Abbvie, Biogen, BMS, Celltrion, Eli Lily, Hospira/Pfizer, MSD, Novartis, Orion Pharma, Roche, Sandoz, UCB, Sanofi and Mylan (not relevant for this abstract)., Speakers bureau: Have received personal fees from Abbvie, Biogen, BMS, Celltrion, Eli Lily, Hospira/Pfizer, MSD, Novartis, Orion Pharma, Roche, Sandoz, UCB, Sanofi and Mylan (not relevant for this abstract)., Robert B.M. Landewé Consultant of: AbbVie; AstraZeneca; Bristol-Myers Squibb; Eli Lilly & Co.; Galapagos NV; Novartis; Pfizer; UCB Pharma, Pedro M Machado Consultant of: PMM: Abbvie, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Roche and UCB, Speakers bureau: PMM: Abbvie, BMS, Lilly, MSD, Novartis, Pfizer, Roche and UCB, Adeline Ruyssen-Witrand Grant/research support from: Abbvie, Pfizer, Consultant of: Abbvie, BMS, Lilly, Mylan, Novartis, Pfizer, Sandoz, Sanofi-Genzyme, Astrid van Tubergen Consultant of: Novartis, Caroline Bastiaenen: None declared, Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli-Lilly, Galapagos, Gilead Sciences, Inc., Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma; Director of Imaging Rheumatology BV

Download Full-text

AB0100 EVALUATION OF PGA LEVEL FOR CLINICAL REMISSION WITH BOOLEAN CRITERIA, 10MM OR 20MM?

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.288 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1078.1-1079

Author(s):

I. Yoshii

Keyword(s):

Disease Activity ◽

Patient Group ◽

Clinical Remission ◽

Global Assessment ◽

Activity Index ◽

T Test ◽

Mean Values ◽

Significant Difference ◽

Remission Criteria ◽

The Mean

Background:Patient’s global assessment (PGA) is one important component of Boolean composite criteria for remission in treat with rheumatoid arthritis (RA). However, PGA no more than 10mm is sometimes obstacle to attain clinical remission. In recent few years, one opinion that PGA no more than 20mm may be comparable as no more than 10mm.Objectives:The aim of this study is to analyze how difference of these PGA level affect disease activity and daily activities in living, and evaluate which is optimal for the remission with Boolean remission criteria from real world setting.Methods:RA patients who were followed up for more than three years in the institute were picked up in the study. Each patient was monitored with tenderness joint count (TJC), swollen joint count (SJC), PGA, evaluator’s global assessment (EGA), serum C-reactive protein level (CRP), calculated disease activity score with simplified disease activity index(SDAI), Health Assessment Questionnaire Disability Index (HAQ-DI), and pain score using visual analog scale (PS-VAS) every consulted time from the first encounter (Baseline). Patients were classified according to achievement of Boolean remission criteria. Group 1: a patient group who attained Boolean remission wih TJC≦1, SJC≦1, CRP≦1mg/dl, and PGA≦1 (G-1), Group 2: a patient group who could not attained the Boolean remission used in the G-1 evaluation, but could attained another Boolean remission with TJC≦1, SJC≦1, CRP≦1mg/dl, and PGA≦2 (G-2), and Group 3: a patient group who could not attain Boolean remission for neither criterion.Mean values of measured parameters at Baseline and after the Baseline were compared statistically with Student T-test. Mean values of the same parameters in the G-1 and G-2 at the time of attain Boolean remission for each criteria, mean values of each of these parameters thereafter, and changes of these parameters were compared statistically with Student T-test.Results:A total of 438 patients 385 in the G-1 group, 16 in the G-2 group, and 37 in the G-3 group, were recruited. In parameters at Baseline, level of TJC, SJC, PGA, EGA, SDAI, and HAQ-DI in the G-1 was significantly lower than in the G-3, whereas no significant differences in any parameters demonstrated between in the G-2 and G-3. Level of HAQ-DI, and PS-VAS after Baseline in the G-1 was lower than in the G-3, whereas no significant difference of these parameters after Baseline demonstrated between in the G-2 and G-3. TJC, SJC, PGA, and EGA demonstrated significant less level in the G-1 than in the other two groups. The mean SDAI score at the time of first achievement of Boolean remission in the G-1 and G-2 were 1.08 and 2.57, respectively. The mean value of SDAI score after remission in the G-1 and G-2 were 3.35 and 6.44, respectively. These values and PS-VAS including change of the SDAI score demonstrated significant difference between the two groups (p<0.01), whereas HAQ-DI in the two groups demonstrated no significant difference.Conclusion:These results suggested that setting PGA as no more than 10mm should be reasonable for the evaluation of clinical remission with the Boolean criteria.Disclosure of Interests:None declared

Download Full-text

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

Arthritis Research & Therapy ◽

10.1186/s13075-021-02566-z ◽

2021 ◽

Vol 23 (1) ◽

Author(s):

Sang Youn Jung ◽

Jung Hee Koh ◽

Ki-Jo Kim ◽

Yong-Wook Park ◽

Hyung-In Yang ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Maintenance Therapy ◽

Disease Activity ◽

Controlled Trial ◽

Tumor Necrosis Factor Inhibitor ◽

Controlled Study ◽

Open Label ◽

Low Disease Activity ◽

Efficacy Analysis ◽

Tnfα Inhibitor

Abstract Background Tapering 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). Methods This 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. Results In 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. Conclusion This 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 registration Korea CDC CRIS, KCT0005868. Registered 4 February 2021—retrospectively registered

Download Full-text

POS0241 VALIDATION OF THE ANKYLOSING SPONDYLITIS DISEASE ACTIVITY SCORE WITH A QUICK QUANTITATIVE C-REACTIVE PROTEIN ASSAY (ASDAS-QCRP) IN PATIENTS WITH AXIAL SPONDYLOARTHRITIS (AXSPA): A PROSPECTIVE, NATIONAL, MULTICENTER STUDY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.2352 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 342.1-342

Author(s):

F. Proft ◽

J. Schally ◽

H. C. Brandt ◽

J. Brandt-Juergens ◽

G. R. Burmester ◽

...

Keyword(s):

Ankylosing Spondylitis ◽

Disease Activity ◽

Disease Activity Score ◽

High Disease Activity ◽

Activity Score ◽

Inactive Disease ◽

Treat To Target ◽

C Reactive Protein ◽

Low Disease Activity ◽

Reactive Protein

Background:According to international recommendations, the Ankylosing Spondylitis Disease Activity Score (ASDAS) is the preferred score for assessing disease activity in axial spondyloarthritis (axSpA) [1]. However, routine determination of C-reactive protein (CRP) to calculate ASDAS values takes hours to days. This limits the use of ASDAS in clinical routine and clinical trials and hinders the implementation of treat-to-target approaches in axSpA. Whereas quick quantitative CRP (qCRP) tests allow CRP assessment within a few minutes. In a pilot project the performance of qCRP-based ASDAS assessment (ASDAS-qCRP) was already investigated in a single center study of 50 newly diagnosed, bDMARD-naïve axSpA patients with promising results [2].Objectives:To validate the ASDAS-qCRP in a prospective, multicenter study of axSpA patients in a typical axSpA cohort with an appropriate sample size.Methods:The study was conducted in five centers in Germany. Consecutive adult (≥ 18 years) axSpA patients were included. In addition to a rheumatological assessment, including patient reported outcomes (PROs), routine CRP and erythrocyte sedimentation rate (ESR) were measured in the local labs. Additionally, a qCRP testing with the „QuikRead go instrument“ (Aidian Oy, Finland) was performed at the study center (measurement range 0.5 - 200 mg/l for hematocrit concentrations of 40 – 45%). Statistical analysis included descriptive statistics, cross tabulation and weighted Cohen´s kappa comparing disease activity categories, Bland-Altman plots and intraclass correlation coefficient (ICC) for ASDAS-CRP and ASDAS-qCRP.Results:In this study 251 axSpA patients were included between January and September 2020 (mean age: 38.4 years; mean disease duration: 6.2 years, 159 patients (63.3%) were male, 211 (84.1%) HLA-B27 positive and 195 (77.7%) were classified as radiographic axSpA). 143 patients (57.0%) were treated with bDMARDs. CRP and qCRP showed mean values of 2.12 and 2.17 mg/l, respectively. With the ASDAS-qCRP, 242 patients (96.4%) were assigned to the same disease activity category as compared to the ASDAS based on the conventional lab CRP measurement (Table 1). Weighted Cohen´s kappa was 0.966 (95%CI: 0.943; 0.988). ICC for ASDAS-CRP- and ASDAS-qCRP-values was 0.997 (95%CI: 0.994; 0.999). The agreement of ASDAS-qCRP and ASDAS-CRP is shown in a Bland-Altman plot (Figure 1).Table 1.Disease activity categories by ASDAS-qCRP vs. ASDAS-CRPASDAS-qCRP (n = 251)Inactive Disease(< 1.3)Low Disease Activity (1.3 - < 2.1)High Disease Activity (2.1 - 3.5)Very high Disease Activity (> 3.5)ASDAS-CRPInactive Disease(< 1.3)56 (22.3%)2 (0.8%)Low Disease Activity (1.3 - < 2.1)62 (24.7%)7 (2.8%)High Disease Activity (2.1 - 3.5)97 (38.6%)Very high Disease Activity (> 3.5)27 (10.8%)The fields highlighted in red indicate that disease activity categories do not match.ASDAS = Ankylosing Spondylitis Disease Activity Score, CRP = C-reactive protein, qCRP = quick quantitative CRPConclusion:The ASDAS-qCRP and ASDAS-CRP showed an almost perfect agreement on the assignment to disease activity categories (96%) with the important advantage of time. With ASDAS-qCRP, rheumatologists could base their clinical decision-making on a disease activity measurement by using a composite score immediately. ASDAS-qCRP, therefore, can be integrated in clinical routine and clinical trials in the future and may facilitate implementation of the treat-to-target concept in axial SpA.References:[1]Smolen JS, et al. Ann Rheum Dis. 2018 Jan; 77(1):3-17.[2]Proft F, et al. Joint Bone Spine. 2019 Jul 29.Figure 1.Bland-Altman plot for ASDAS-qCRP and ASDAS-CRPAcknowledgements:The authors would like to deeply thank Braun T, Doerwald C, Deter N, Höppner C, Lackinger J, Lorenz C, Lunkwitz K, Mandt B, Sron S and Zernicke J for their practical support and coordinating the study.Funding statement: The AQUA study was supported by an unrestricted research grant from Novartis. Testing kits were provided free of charge from Aidian Oy, Finland.Disclosure of Interests:None declared

Download Full-text