Methotrexate therapy in rheumatoid arthritis. A two year prospective follow-up

1990 ◽  
Vol 9 (3) ◽  
pp. 333-341 ◽  
Author(s):  
A. A. Drosos ◽  
D. Psychos ◽  
A. P. Andonopoulos ◽  
S. Stefanaki-Nikou ◽  
E. B. Tsianos ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Methotrexate Therapy

scholarly journals Superficial Ulcerating Rheumatoid Necrobiosis Associated with Methotrexate Use in a Patient with Rheumatoid Arthritis

2020 ◽  
Keyword(s):  
Rheumatoid Arthritis ◽  
Genetic Predisposition ◽  
Methotrexate Therapy ◽  
Rheumatologic Disease ◽  
Therapy Discontinuation ◽  
Therapy Initiation ◽  
Dermatological Side Effects ◽  
Dermatologic Manifestations ◽  
Caucasian Female

Methotrexate, a disease-modifying antirheumatic drug, is fundamental to limiting progression in several rheumatic diseases such as rheumatoid arthritis (RA). However, methotrexate is also associated with various significant adverse effects. Of note, there are several dermatologic manifestations attributed to methotrexate therapy. In particular, accelerated nodulosis and panniculitis are linked to methotrexate therapy in the current literature. The authors present the case of a 55-year-old Caucasian female with seropositive erosive RA who developed superficial ulcerating rheumatoid necrobiosis (SURN), secondary to methotrexate therapy. The patient’s treatment consisted of methotrexate discontinuation, topical clobetasol, and initiation of leflunomide as a replacement of methotrexate. Follow-up evaluation confirmed resolution of SURN over time and maintained low disease RA activity with leflunomide.Few cases describe SURN in the setting of RA and there are currently no cases published that suggest methotrexate’s possible role in SURN. Methotrexate-induced SURN is plausible in this case because of the correlation with therapy initiation and remission after therapy discontinuation. SURN has significant histological overlap with other methotrexate-induced dermatologic manifestations, allowing for a possible correlation. Most dermatological side effects of methotrexate are linked to a genetic predisposition of the HLA-DRB1 gene. Additionally, methotrexate’s mechanism of action for rheumatologic disease paradoxically stimulates adenosine-1 receptors and activates neutrophil chemotaxis and phagocytosis. Adenosine-1 receptor stimulation is hypothesised to be the source of rheumatoid-accelerated nodulosis and possibly SURN. Furthermore, the location of manifestation, genetic predisposition, and comorbid features in the patient all possibly have a role in this unique dermatological side effect.

scholarly journals POS0677 THE ROLE OF MUSCULOSKELETAL ULTRASOUND IN PREDICTING THE RESPONSE TO JAK INHIBITORS: RESULTS FROM A LARGE MONOCENTRIC COHORT

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 583-583
Author(s):  
C. Garufi ◽  
F. Ceccarelli ◽  
F. R. Spinelli ◽  
S. Mancuso ◽  
C. Pirone ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Structural Damage ◽  
Power Doppler ◽  
Response To Treatment ◽  
Jak Inhibitors ◽  
Inflammatory Score ◽  
Inflammatory Status

Background:In the management of chronic arthritis, such as Rheumatoid Arthritis (RA), Ultrasound (US) assessment can provide relevant information about the joint inflammatory status in the diagnostic phase and even more in the monitoring of disease activity and structural damage1,2.Objectives:In this longitudinal study, we aimed to assesse the role of US in predicting the efficacy of JAK-inhibitors (JAKi) in RA patients.Methods:We enrolled RA patients starting baricitinib or tofacitinib. All patients were evaluated at baseline and after 4, 12, 24, 48 weeks. Disease activity was calculated by DAS28CRP. US examination in 22 joints (I–V MCPs and PIPs, wrists) aimed at evaluating inflammatory features (synovial effusion and hypertrophy, power Doppler-PD), through a semi-quantitative scale (0-3). The total US (0-198) and PD (0-66) scores were calculated. We scanned bilateral flexor (I–V fingers of hands) and extensor compartments (1-6) tendons: tenosynovitis was scored as absent/present (0/1), resulting in a total score (0-22).Results:We studied 102 patients (M/F 15/87; median age 59.2 years, IQR 17.75; median disease duration 144 months, IQR 126), 61 treated with baricitinib and 41 with tofacitinib. At baseline, the median total US score was 18 (IQR 19) and the median PD score 2 (4). We observed a significant reduction in both total and PD US scores at all time-points (p<0.0001) (Figure 1). At baseline, 75.4% of patients showed tenosynovitis involving at least one tendon, with a median score of 2 (IQR 3.5) significantly decreasing after 24 weeks (p=0.02). Multivariate analysis, adjusted for baseline DAS28CRP and other concomitant treatments (including glucocorticoids and methotrexate treatment), confirmed the independent association between baseline US (PD and tenosynovitis) scores and the reduction of disease activity at follow-up evaluations.Conclusion:The present study confirmed the early efficacy of JAKi in RA patients by using US evaluation. Furthermore, power doppler and tenosynovitis scores could play a predictive role in response to treatment.References:[1]MUELLER RB, HASLER C, POPP F, et al. Effectiveness, Tolerability, and Safety of Tofacitinib in Rheumatoid Arthritis: A Retrospective Analysis of Real-World Data from the St. Gallen and Aarau Cohorts. J Clin Med. 2019;8(10):1548.[2]COLEBATCH AN, EDWARDS CJ, ØSTERGAARD M, et al. EULAR recommendations for the use of imaging of the joints in the clinical management of rheumatoid arthritis. Ann Rheum Dis. 2013;72(6):804-14.Figure 1.Ultrasound inflammatory score (a) and Ultrasound Power Doppler (PD) score (b) at baseline and follow-up.Table 1.Baseline characteristics of 414 RA patients.WEEKS04122448US inflammatory score18 (19)11 (15.5)9.5 (11.7)7.5 (8)6 (11)US PD score2 (4)0 (2)0 (1)0 (1)0 (0.7)Disclosure of Interests:Cristina Garufi: None declared, Fulvia Ceccarelli: None declared, Francesca Romana Spinelli Speakers bureau: Abbvie, Eli Lilly, Consultant of: Gilead/Galapagos, Eli Lilly, Grant/research support from: Pfizer, Silvia Mancuso: None declared, Carmelo Pirone: None declared, Fabrizio Conti Speakers bureau: Abbvie, Eli Lilly, Sanofi, Pfizer, Consultant of: Gilead/Galapagos

scholarly journals POS1234 IMPACT OF THE CHANGE IN ADMINISTRATION ROUTE OF TOCILIZUMAB AND ABATACEPT, DUE TO THE COVID-19 LOCKDOWN ON DISEASE ACTIVITY IN PATIENTS WITH RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 900.1-900
Author(s):  
L. Diebold ◽  
T. Wirth ◽  
V. Pradel ◽  
N. Balandraud ◽  
E. Fockens ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Physical Activity ◽  
Disease Activity ◽  
Univariate Analysis ◽  
Route Of Administration ◽  
Anxiety And Depression ◽  
Administration Route ◽  
Factors Associated ◽  
The Impact

Background:Among therapeutics used to treat rheumatoid arthritis (RA), Tocilizumab (TCZ) and Abatacept (ABA) are both biologic agents that can be delivered subcutaneously (SC) or intravenously (IV). During the first COVID-19 lockdown in France, all patients treated with IV TCZ or IV ABA were offered the option to switch to SC administration.Objectives:The primary aim was to assess the impact of changing the route of administration on the disease activity. The second aim was to assess whether the return to IV route at the patient’s request was associated with disease activity variation, flares, anxiety, depression and low physical activity during the lockdown.Methods:We conducted a prospective monocentric observational study. Eligibility criteria: Adult ≥ 18 years old, RA treated with IV TCZ or IV ABA with a stable dose ≥3 months, change in administration route (from IV to SC) between March 16, 2020, and April 17, 2020. The following data were collected at baseline and 6 months later (M6): demographics, RA characteristics, treatment, history of previous SC treatment, disease activity (DAS28), self-administered questionnaires on flares, RA life repercussions, physical activity, anxiety and depression (FLARE, RAID, Ricci &Gagnon, HAD).The primary outcome was the proportion of patients with a DAS28 variation>1.2 at M6. Analyses: Chi2-test for quantitative variables and Mann-Whitney test for qualitative variables. Factors associated with return to IV route identification was performed with univariate and multivariate analysis.Results:Among the 84 patients who were offered to switch their treatment route of administration, 13 refused to change their treatment. Among the 71 who switched (48 TCZ, 23 ABA), 58 had a M6 follow-up visit (13 lost of follow-up) and DAS28 was available for 49 patients at M6. Main baseline characteristics: female 81%, mean age 62.7, mean disease duration: 16.0, ACPA positive: 72.4%, mean DAS28: 2.01, previously treated with SC TCZ or ABA: 17%.At M6, the mean DAS28 variation was 0.18 ± 0.15. Ten (12.2%) patients had a DAS28 worsening>1.2 (ABA: 5/17 [29.4%] and TCZ: 5/32 [15.6%], p= 0.152) and 19 patients (32.8%) had a DAS28 worsening>0.6 (ABA: 11/17 [64.7%] and TCZ: 8/32 [25.0%], p= 0.007).At M6, 41 patients (77.4%) were back to IV route (26 TCZ, 15 ABA) at their request. The proportion of patients with a DAS28 worsening>1.2 and>0.6 in the groups return to IV versus SC maintenance were 22.5%, 42.5% versus 11.1% and 22.2% (p=0.4), respectively. The univariate analysis identified the following factors associated with the return to IV route: HAD depression score (12 vs 41, p=0.009), HAS anxiety score (12 vs 41, p=0.047) and corticosteroid use (70% vs 100%, p=0.021), in the SC maintenance vs return to IV, respectively.Conclusion:The change of administration route of TCZ and ABA during the first COVID-19 lockdown was infrequently associated with a worsening of RA disease. However, the great majority of the patients (77.4%) request to return to IV route, even without disease activity worsening. This nocebo effect was associated with higher anxiety and depression scores.Disclosure of Interests:None declared

scholarly journals O06 Baseline predictors of methotrexate-related adverse events in methotrexate-naïve patients with RA

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Ahmad A Sherbini ◽  
James M Gwinnutt ◽  
Kimme L Hyrich ◽  
Suzanne M M Verstappen ◽  
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Events ◽  
Health Assessment ◽  
Prevalence Rates ◽  
Clinical Predictors ◽  
Research Support ◽  
Related Data ◽  
Increased Risk ◽  
One Year

Abstract Background/Aims  Methotrexate (MTX) is the most common treatment for rheumatoid arthritis (RA). The prevalence of adverse events (AEs) associated with MTX treatment for RA have been studied extensively, but there are limited data on the predictors of these AEs. This study aims to summarise the prevalence rates of MTX AEs, including gastrointestinal (GI), neurological, mucocutaneous, and elevated alanine transaminase (ALT) enzyme, and to identify baseline demographic and clinical predictors of these AEs. Methods  The Rheumatoid Arthritis Medication Study (RAMS) is a UK multi-centre prospective cohort study of patients with RA starting MTX for the first time. Relevant demographic, medication, clinical and disease related data were collected at baseline. AEs were reported at six and twelve months follow-ups. The prevalence rates of AEs were calculated based on the proportions of patients who reported having had an AE within one year of follow-up. The associations between candidate baseline predictors and AEs were assessed using multivariable logistic regression. Results  A total of 2,089 patients were included with a mean age of 58.4 (standard deviation: 13.5) years, 1390 (66.5%) were women. 1,814 and 1,579 patients completed the 6 and 12 months follow-up visits, respectively. The prevalence rates of the AEs within one year of follow-up were: GI = 777 (40.6%), mucocutaneous = 441 (23.1%), neurological = 487 (25.5%), elevated ALT (&gt; upper limit of normal [ULN]) = 286 (15.5%). Younger age and being a woman were associated with increased risk of GI AEs, (age: OR 0.97 per year increase in age, 95% CI 0.98, 1.00; male sex: OR 0.58 vs female, 95% CI 0.46, 0.74) (Table 1). Higher baseline Health Assessment Questionnaire (HAQ) score was an independent predictor of GI, mucocutaneous, and neurological AEs. Furthermore, having ALT &gt;1xULN at baseline or history of diabetes was associated with increased risk of subsequent ALT elevation during the study follow-up. Conclusion  In patients with RA starting MTX, GI AEs were the most commonly reported AEs during the first year of follow-up. The identified predictors of AEs may facilitate discussions between clinicians and patients prior to commencing MTX, and may lead to increased adherence and consequently improved effectiveness. Disclosure  A.A. Sherbini: None. J.M. Gwinnutt: Grants/research support; BMS. K.L. Hyrich: Member of speakers’ bureau; Abbvie. Grants/research support; Pfizer, UCB, BMS. S.M.M. Verstappen: Consultancies; Celltrion. Member of speakers’ bureau; Pfizer. Grants/research support; BMS.

scholarly journals AB0144 PREDICTIVE FACTORS OF SUSTAINED CLINICAL REMISSION IN RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1099.2-1099
Author(s):  
R. Fakhfakh ◽  
N. El Amri ◽  
K. Baccouche ◽  
H. Zeglaoui ◽  
E. Bouajina
Keyword(s):  
Rheumatoid Arthritis ◽  
Predictive Factors ◽  
Clinical Remission ◽  
Power Doppler ◽  
Health Assessment ◽  
Sustained Remission ◽  
Sharp Score ◽  
Remission Criteria ◽  
Ultrasound Parameters

Background:Sustained remission (SR) is an ultimate treatment goal in the management of patients with rheumatoid arthritis (RA) (1) and is associated with better RA prognosis, reflected by the quality of life, physical function and radiographic progression (2).Objectives:To investigate the prevalence and predictors of SR in RA patients.Methods:A longitudinal prospective study of patients with RA. At the inclusion, the patients were in remission DAS28 ESR≤ 2.6 for at least 6 months. A B-mode and power doppler (PD) ultrasound of 42 joints and 20 tendons was performed. Synovial hypertrophy (SH) and tenosynovitis in B-mode and PD were defined and scored from 0 to 3 using the OMERACT. The CDAI, SDAI, Boolean remission criteria, the health assessment questionnaire (HAQ) and the radiological Sharp score were calculated. Then, the DAS28 erythrocyte sedimentation rate (ESR) was evaluated at 6 and 12 months. SR was defined as the persistence of a DAS28 ESR≤2.6 at 6 or 12 months without any change in RA therapy during the follow-up. Unstable remission (UR) was defined either as DAS28 ESR > 2.6 at 6 or 12 months or an increase in RA therapy because of a relapse during the follow-up.Results:At baseline, thirty-seven patients were included. At 6 and 12 months, 28 and 24 patients completed follow-up, respectively. In decreasing order, Boolean remission (92.2%), DAS28ESRremission (85.7%), SDAI remission (85%) and CDAI remission (83.3%) achieved SR at 6 months. At 12 months, SR was found in 100% in Boolean remission, 87.5% in SDAI remission, 86.7% in CDAI remission and in 79.7% in DAS28 ESR remission. At 6 months, only the ESR (17mm/1h in SR versus 32 mm/1h in UR, p=0.04) was associated with SR. The disease duration, remission duration, swollen and tender joints, DAS28ESR, HAQ, rheumatoid factor, radiological Sharp score and ultrasound parameters weren’t associated with SR. At 12 months, the squeeze test (15% in SR vs 80% in UR, P=0.01), the ESR (15 mm/1h in SR versus 30 mm/1h in UR, p=0.03), the Boolean remission (61.1% in SR versus 0% in UR, p=0.04) and the DAS28ESR (mean: 1.8 in SR versus 2.5 in UR, P=0.01) were associated with SR. However, no association was found with radiological Sharp score and ultrasound parameters. On multivariate analysis, the ESR (OR=1.13, CI95%=1.01-1.2, p=0.03) and the Squeeze test (OR=21.3, CI95%=1.7-263, p=0.01) were predictors of SR, at 12 months.Conclusion:At 6 and 12 months, 79.7%-85.7% of patients in DAS28 ESR remission achieved sustained remission, respectively. Boolean and DAS28 ESR remission were associated with SR. Unlike DAS28 ESR, Boolean remission seems to reflect more the SR. The squeeze test and the ESR were predictors’ factor. However, the radiological and the ultrasound parameters didn’t show any association.References:[1]Ajeganova S, Huizinga T. Sustained remission in rheumatoid arthritis: latest evidence and clinical considerations. Ther Adv Musculoskelet Dis. 2017;9(10):249-62.[2]Xie W, Li J, Zhang X, Sun X, Zhang Z. Sustained clinical remission of rheumatoid arthritis and its predictive factors in an unselected adult Chinese population from 2009 to 2018. Int J Rheum Dis. 2019;22(9):1670-8.Disclosure of Interests:None declared

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