A comparative study of total knee arthroplasty outcome for stiff knee with or without sequential antirheumatic drug treatment

Background The aim of this study was to evaluate the influence of antirheumatic drug treatment on knee function of stiff knee patients after total knee arthroplasty (TKA). Methods Twenty-seven patients (44 knees) of active RA (rheumatoid arthritis) or AS (ankylosing spondylitis) with stiff knees were included in this study. And they were divided into two groups according to continue antirheumatic drug treatment or not after TKA: the therapeutic group (16 patients, 27 knees) and the controlled group (11 patients, 17 knees). The outcomes were assessed by Knee Society Score (KSS), Visual Analogue Scale (VAS), range of motion (ROM) (at week 6, month 6, year 1, and year 2), “Forgotten Joint” Scale (FJS), with or without crutch, satisfaction, and revision (at year 2). The knee prosthetic loosening was evaluated by the followed X-ray at each following time. Results The mean follow-up time was 51 months (34–69 months). The KSS was higher at week 6 after TKA in the therapeutic group (p < 0.05); however, the functional scores of KSS at month 6, year 1, and year 2 in the controlled group were more points improved. The therapeutic patients preferred the knee more at month 6, year 1, and year 2. The differences of KSS clinical scores (at month 6, year 1, and year 2), VAS, ROM, Crutch and FJS between the two groups were not statistically significant (p > 0.05). Conclusion For patients with stiff knees, the sequential antirheumatic drug treatment after TKA had no obvious effect on postoperative KSS, but can improve the satisfaction. Level of evidence Therapeutic level II. See Instructions for Authors for a complete description of levels of evidence.

A Comparative Study of Total Knee Arthroplasty Outcome for Stiff Knee with or without Sequential Antirheumatic Drug Treatment

BackgroundTo evaluate influence of antirheumatic drug treatment on knee function of patients with stiff knee after total knee arthroplasty (TKA). MethodsTwenty-seven patients (44 knees) of active RA (rheumatoid arthritis) or AS (ankylosing spondylitis) with stiff knee were included in this study. And they were divided into two groups according to continue antirheumatic drug treatment or not after TKA: the therapeutic group (16 patients, 27 knees) and the controlled group (11 patients, 17 knees). The outcomes were assessed by Knee Society Score (KSS), Visual Analogue Scale (VAS), range of motion (ROM) (at week 6, month 6, year 1 and year 2), “Forgotten Joint” Scale (FJS), with or without crutch, satisfaction and revision (at year 2). The knee prosthetic loosening was evaluated by the followed X-ray at each following time. ResultsThe mean follow-up time was 51 months (34-69 months). The KSS were higher at week 6 after TKA in the therapeutic group (p < 0.05), however, the functional scores of KSS at month 6, year 1 and year 2 in the controlled group were more points improved. The therapeutic patients preferred the knee more at month 6, year 1 and year 2. The differences of KSS clinical scores (at month 6, year 1 and year 2), VAS, ROM, Crutch and FJS between the two groups were not statistically significant (p＞0.05). ConclusionFor patients with stiff knees, the sequential antirheumatic drug treatment after TKA had no effect on postoperative KSS, but can improve the satisfaction.Level of evidenceTherapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Disease Activity in Disease Modifying Anti-Rheumatic Drug (DMARD) Naïve Rheumatoid Arthritis Patients in A Subset of Karachi Population

Background: Rheumatoid arthritis (RA) is a progressive inflammatory disease affecting the joints with a marked impact upon functional capacity of the patient. The working ability of RA patients can be preserved if the disease modifying antirheumatic drug (DMARD) therapy is initiated early in the course of disease. The objective of our study was to compare the disease activity variables in DMARD-naïve seropositive rheumatoid arthritis (SPRA) and seronegative rheumatoid arthritis (SNRA) patients and to determine correlations between the disease activity variables in RA. Methods: A cross-sectional study recruited n=90 patients from Rheumatology Clinic from May 2020 to October 2020. The rheumatoid factor (RF), anti-cyclic citrullinated peptide levels (ACCP), erythrocyte sedimentation rates (ESR) were clinically measured. Disease activity variables including the tender joint count (TJC), swollen joint count (SJC), health assessment questionnaire-disability index (HAQ-DI) and disease activity score of 28 joints (DAS28) were consistently calculated. Patients were divided into seropositive RA group and seronegative RA group, based on RF and ACCP. Chi squared test and Pearson correlation were applied, p≤0.05 was considered statistically significant. Results: High HAQ-DI and DAS28-ESR scores were found in SPRA than in the SNRA patients and were statistically significant (p=0.000, p=0.054). TJ-28 and SJ-28 counts were higher in SPRA but were not statistically significant. There was a significant correlation of DAS28 with TJ-28 (r=0.816, p-value = 0.000), with SJ-28(r=0.801, p-value = 0.000) and HAQ-DI (r=0.517, p-value = 0.000). Conclusion: Evaluation of inflammatory markers and functional disability was found significant (p=0.000) in determining the disease activity compared to presence of autoantibodies in DMARD naïve RA patients. Keywords: Disease Modifying Antirheumatic Drug; Arthritis; Rheumatoid Factor; Autoimmune Diseases.

Lack of association between CYB5A gene rs1790834 polymorphism and the response to leflunomide in women with rheumatoid arthritis

Aim Leflunomide is a disease-modifying antirheumatic drug used in therapy for rheumatoid arthritis (RA). Previous studies indicated that oestrogens and androgens may affect the response to leflunomide in RA patients. The synthesis of androgens is regulated by cytochrome CYB5A. The aim of this study was to examine the association between the CYB5A gene rs1790834 polymorphism and the response to leflunomide in women with RA. Methods The study included 111 women diagnosed with RA. Leflunomide was administered in monotherapy at a dose of 20 mg/day. All patients underwent a monthly evaluation for 12 months after the initiation of treatment with leflunomide. Results After 12 months of therapy, the changes in individual disease activity parameters, such as: DAS28, ESR, CRP and VAS, were not statistically significantly different between rs1790834 genotypes in the Kruskal–Wallis test. Conclusions The results of our study suggest lack of statistically significant association between the CYB5A gene rs1790834 polymorphism and the response to leflunomide in women with RA.

AB0129 IL-6R GENETIC VARIANTS AS PREDICTORS OF CLINICAL RESPONSE TO TOCILIZUMAB IN RHEUMATOID ARTHRITIS PATIENTS

Background:Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory autoimmune disease of unknown etiology. Tocilizumab (TCZ) is a first-line biological disease-modifying anti-rheumatic drug (bDMARD) which inhibits Interleukin 6 (IL-6) pathway through blockade of its receptor. At present, there is a lack of evidence to recommend the treatment of one bDMARD over another.(1) Seeking for genetic biomarkers to predict response to treatment could be key towards a personalized treatment strategy in rheumatology.(2)Objectives:We aimed to evaluate whether functional single nucleotide polymorphisms (SNPs) in the IL6R gene could predict response and/or toxicity to TZC in Caucasian patients diagnosed with RA.Methods:Retrospective analytical preliminar study of a cohort of 31 patients diagnosed with RA (ACR/EULAR 2010 criteria) who received treatment with TCZ within the last 10 years. Epidemiological, clinical and laboratory data were collected. DNA was extracted from EDTA blood samples. Three SNPs in the IL-6 receptor gene (rs12083537, rs2228145, rs4329505) were genotyped by real-time PCR with TaqMan probes. The associations between polymorphisms and clinicopathological features were evaluated using parametric tests. Efficacy was assessed as the difference of DAS-28 CRP at 6 months. The toxicities recorded were hepatotoxicity, infections, hypersensibility, gastrointestinal, hematological and dyslipidemia.Results:The 31 DNA samples from patients included were mainly female (83.9%) and had a mean age at diagnosis of 46.8 years. The mean duration of treatment was 51.3 months and, previously to initiate TCZ, they received a mean of 2,6 csDMARD and 1,7 bDMARD.The more frequent adverse effects were hypertransaminasemia (22.6%) and neutropenia (32.3%). Most relevant epidemiologic and clinical data is shown in Table 1.Table 1.Clinical characteristics. RA=Rheumatoid Arthritis. CCP= anti-Cyclic Citrullinated Peptides. RF=Rheumatoid factor. csDMARDs= conventional synthetic Disease-modifying antirheumatic drug. bDMARD= biological Disease-modifying antirheumatic drug. BMI=Body Mass Index. Sc=subcutaneous. Ev=endovenous. DAS28= Disease Activity Score in 28 jointsSex (n=31), n (% women/men) 26/5 (83,9%/16,1%)Age at diagnosis (n=31), years +- SD 46,8+- 12,8Erosive RA (n=31), n(%) 14 (45,2%)Anti-CCP positive (n=31), n(%)UI+- SD 23 (74,2%)259,7 +- 137,3RF positive (n=31), n (%)UI+-SD 21 (67,7%)189,4+- 114Previous csDMARD (n=31), n°+-SD2,6 +-1,3Previous bDMARD (n=31), n°+- SD1,7 +- 1,4BMI (n=29), mean +- SD29,3+- 5,1Duration of treatment (n=31), months +-SD51,3 +- 36,3-Active treatment (n=12)-80,9+- 18,3-Finished treatment (n=19)-32,6+- 32,2Route of administration (n=31), n (%) sc/ev 11/20 (35,5/64,5)Basal DAS28 (n=30), mean+- SD5,3 +- 1,1DAS28 reduction at 6 months (n=28), mean+-SD2,9 +-1,1The univariate analyses showed that the rs2228145 variant was statistically associated with differences in DAS28 reduction at 6 months (p=0.042). Regarding efficacy, we also found a trend with the SNP rs4329505 (p=0.173), which could achieve statistical significance with the projected inclusion of more patients. No associations were found regarding adverse effects.Conclusion:The rs2228145 polymorphisms in the IL6R gene may be considered as a pharmacogenetic biomarker of TCZ response in RA patients. More studies are required in order to investigate the clinical use of pharmacogenetic biomarkers in rheumatic diseases.References:[1]Smolen, Josef S., Robert B., et al. 2020. “EULAR Recommendations for the Management of Rheumatoid Arthritis with Synthetic and Biological Disease-Modifying Antirheumatic Drugs: 2019 Update.” Annals of the Rheumatic Diseases 79 (6): 685–99.[2]Tarnowski, Maciej, Agnieszka Paradowska-Gorycka, et al. 2016. “The Effect of Gene Polymorphisms on Patient Responses to Rheumatoid Arthritis Therapy.” Expert Opinion on Drug Metabolism & Toxicology 12 (1): 41–55.Disclosure of Interests:None declared

AB0483 CAN WE PREDICT WHICH PATIENTS WITH SPONDYLOARTHRITIS WILL NEED DOSE ESCALATION OF SECUKINUMAB TO 300 mg MONTHLY?

Background:Secukinumab is a fully human monoclonal antibody against interleukin-17A, approved in several countries for the treatment of ankylosing spondylitis (AS) and psoriatic arthritis. It is known that some patients benefit from increasing the monthly dose of secukinumab from 150mg, the most commonly used dose, to 300mg. However, the baseline clinical characteristics that differentiate these patients are not yet fully understood.Objectives:This study aimed to investigate whether there are any variables at the beginning of biologic therapy that might predict a greater probability of having to increase the dose of secukinumab to 300mg in order to obtain a response to treatment.Methods:This is a retrospective cohort study, including all the spondyloarthritis and psoriatic arthritis patients under secukinumab at our Rheumatology Department and registered in the national database (Reuma.pt).Demographic, clinical and laboratorial characteristics and disease activity measures were collected from the first visit before the patient began secukinumab. For comparison between the 2 groups, continuous variables were analyzed using Mann-Whitney U and T-tests and categorical variables were analyzed using a Chi-square test. Multivariate regression analyses assessed the impact of selected variables on the need to increase the dose of secukinumab to 300mg.Results:Thirty-two patients with a mean age of 53±11.96 years were included, 19 (58%) were females and 16 (48.5%) had psoriasis. Twenty-seven (81.8%) patients were under a nonsteroidal anti-inflammatory drug (NSAID), 11(33.3%) were under corticosteroid and 11(33.3%) were under conventional synthetic disease-modifying antirheumatic drug (csDMARD); 25 (75,8%) had previously been treated with a biological disease-modifying antirheumatic drug (bDMARD). The mean patient baseline VAS and physician baseline VAS were 74,39±19,77 and 47,55±23,38, respectively; the mean erythrocyte sedimentation rate (ESR) and C-Reactive Protein (CRP) were 26,33±22,62 mm/hr and 10,81±16,88 mg/dL, respectively; the mean swollen joint count (SJC) and tender joint count (TJC) were 1,30±1,63 and 3,67±3,14, respectively; the mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) were 6,18±2,06 and 3,41±0,84, respectively; the mean Bath Ankylosing Spondylitis Metrological Index (BASMI) and Bath Ankylosing Spondylitis Functional Index (BASFI) were 4,22±1,58 and 6,28±2,53, respectively; the mean Maastrich Ankylosing Spondylitis Enthesitis Score (MASES) was 2,85±3,23.Nineteen patients (57.6%) had the dose of secukinumab increased to 300mg. At the baseline visit, the group of patients which had their secukinumab monthly dose increased to 300mg were more frequently men (12 vs 2, p=0.005) and had psoriasis (12 vs 4, p=0.049). On the other hand, these patients also exhibited lower MASES values (2±1.089 VS 4±0.501, p=0.022).A regression analysis was conducted, estimating the relationships between the outcome binary variable of the monthly dose of secukinumab and the following predictors: gender, psoriasis, MASES value and use of corticosteroid. Female gender (OR 0.070, CI95% 0.005-0.890; p=0.040) and absence of psoriasis (OR 0.104, CI95% 0.011-0.952; p=0.045) were predictors for maintaining secukinumab at a dose of 150mg monthly.Conclusion:Our data suggest that the most common characteristics of patients in need of increasing the monthly dose of secukinumab from 150 to 300 mg to achieve a better treatment response are: male gender, coexistence of psoriasis and lower MASES value at baseline. The first two variables remained statistically significant in a multivariate model of regression analysis. Nonetheless, we insist it is of paramount importance to conduct larger studies to confirm these findings.References:[1]Deodhar A, et all. Long-term safety of secukinumab in patients with moderate-to-severe plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis. Arthritis Res Ther. 2019 May 2;21(1):111.Disclosure of Interests:None declared.