scholarly journals AB0224 SUSTAINABLE LOW DISEASE ACTIVITY IN PATIENTS WITH RHEUMATOID ARTHRITIS: REAL-WORLD EXPERIENCE WITH TOCILIZUMAB

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1138.1-1138
Author(s):  
T. Shivacheva ◽  
T. Georgiev ◽  
S. Hristova ◽  
S. Dimitrov ◽  
S. Bogdanova-Petrova ◽  
...  

Background:Sustainability, the ability of drugs to maintain remission or low disease activity (LDA) in patients with rheumatoid arthritis (RA), plays a crucial role for the prevention of structural damage to joints and thus, preserving patients’ functional capacity, health-related quality of life and general sense of well-being. Therefore, studying the sustainable effectiveness of tocilizumab (TCZ) as a monotherapy or combined with methotrexate (MTX) is important (1).Objectives:We aimed to examine to what extend TCZ, alone or combined with MTX, could achieve and further sustain LDA in patients with long-standing RA in the light of current, strictly index-based definitions of LDA and to compare the two versions of DAS28 in patients in real clinical practiceMethods:85 RA patients treated with TCZ for at least eighteen months were consecutively enrolled in the present single-center, retrospective cohort study. All participants met the 1987 ACR classification criteria and attended the rheumatology department of University Hospital “St. Marina” Varna in an outpatient setting. Patients receiving pre-filled syringe contained 162 mg TCZ once weekly subcutaneously. Real-world data were extracted and analyzed from patient’s full medical file. For each visit, disease activity score 28 with ESR and CRP (DAS28-ESR and DAS28-CRP) and simple disease activity index (SDAI) were calculated simultaneously according to generally adopted formulas. A twelve-month result was determined for sustained LDA at each of the patient’s three visits (at 6-month intervals), according to DAS28 and SDAI. Descriptive statistics, Chi square test, Cochran´s Q test, kappa statistic were used, a binary logistics model was compiled to study the impact. Significance level of p <0.05.Results:Two hundred fifty-five patient visits were analyzed. The mean durations of RA and treatment with TCZ were 12.6 (±9.6) years and 3.64 (±1.8) years, respectively. The mean age of patients was 60.3 years (37-87 years), 80% were women, 24.7% were obese, 65.9% have concomitant hypertension. 61.2% of patients are treated with combination therapy TCZ with MTX.Of all patients, these with a sustained 12-month LDA were 41.2%, 28.2% or 23.5% depending on the studied index (DAS28-CRP, SDAI, or DAS28-ESR, respectively).A 12-month SDAI LDA was found in a significantly small proportion of patients (28.2%, p = 0.001). The DAS28 ESR determined a proportion similar to SDAI (23.5%, p> 0.05), while according to the DAS28 CRP, patients with a sustained 12-month LDA were significantly more (41.2% p = 0.005). A moderate level of agreement was found between the assessments of SDAI and the two variants of DAC28 when determining 12-month results of Tocilizumab treatment (DAS28-ESR k = 0.511, p <0.001 and DAC28-CRP k = 0.618, p <0.001). No relationship was found between the combination of TCZ with MTX and the patients’ chance of a sustained 12-month LDA, regardless of which index the result was measured.Patients with hypertension were significantly less likely to have sustained 12-month LDA according to SDAI and DAS 28 ESR (OR 0.135, 95% CI 0.048-0.386; OR 0.313, 95% CI 0.111-0.882, respectively), but not according to DAS28 CRP.Conclusion:Sustained 12- month LDA with TCZ in patients with long-term RA remains uncommon in daily clinical practice. Co-administration of MTX is not associated with an increased likelihood of achieving a sustained LDA in the analysis of long-term responses. Patients with concomitant hypertension are less likely to be in a sustained 12-month LDA, according to SDAI and DAS28-ESR. The results according to DAS28 ESR, but not according to DAS28CRP are comparable to those of SDAI when measuring long-term results of treatment with TCZ.References:[1]Hamann PDH, Pauling JD, McHugh N, Shaddick G, Hyrich K; BSRBR-RA Contributors Group. Predictors, demographics and frequency of sustained remission and low disease activity in anti-tumour necrosis factor-treated rheumatoid arthritis patients. Rheumatology (Oxford). 2019 Dec 1;58(12):2162-2169.Disclosure of Interests:None declared

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1406.1-1407
Author(s):  
S. H. Nam ◽  
J. S. Lee ◽  
S. J. Choi ◽  
W. J. Seo ◽  
J. S. Oh ◽  
...  

Background:Several recent studies have reported that MTX could be discontinued in patients with low disease activity who are taking biologic DMARDs or tofacitinib. However, there are limited studies on whether MTX could be discontinued in patients with low disease activity who have taken MTX for a long term.Objectives:We investigated the disease flare rate in patients with rheumatoid arthritis (RA) who achieved low disease activity following long-term methotrexate (MTX) treatment and the factors related to flare.Methods:This retrospective longitudinal cohort study included patients with RA and low disease activity who were exposed to MTX for >10 years. Disease flare was defined as an increase in DAS28 of >1.2 within 6 months of discontinuation of MTX. Logistic regression analysis was performed to identify the factors associated with flare.Results:In total, 97 patients with RA were included in the study. The mean baseline DAS28 was 1.96 ± 0.56. The median cumulative MTX dose was 11.7g; the median duration of exposure to MTX was 19 years. Following MTX discontinuation, flare occurred in 43 (44.3%) patients; the mean time to flare was 98 ± 37.7 days. According to univariable logistic regression analysis, C-reactive protein, erythrocyte sedimentation rate (ESR) at discontinuation, the average ESR in the 6 months before discontinuation of MTX, a weekly dose of MTX before discontinuation, and use of other conventional synthetic DMARDs were associated with a higher risk of disease flare. In multivariable analysis, a weekly dose of MTX before discontinuation (OR, 1.014; 95% CI, 1.014–1.342; p = 0.031) was significantly associated with flare risk.Conclusion:Among patients with RA who achieved low disease activity with long-term treatment with MTX, more than half of the patients remained flare free after MTX discontinuation. A higher MTX dose before discontinuation was associated with a high flare risk.Disclosure of Interests:None declared


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1134.2-1134
Author(s):  
V. Rybakova ◽  
A. Avdeeva ◽  
Y. Olyunin ◽  
E. Nasonov

Background:Current guidelines for the treatment of rheumatoid arthritis (RA) recommend early administration of methotrexate (MTX) and addition of a biologic if MTX monotherapy does not provide remission or low activity of the disease. Efficacy of this strategy in real clinical practice was assessed using data from the Russian RA registry OREL.Objectives:To analyze long-term results of intensive treatment initiated at RA onset in real clinical practice.Methods:141 RA patients with disease duration less than 3 years (29 men, 112 women) were included. 112 were positive for rheumatoid factor and 119 – for anti-cyclic citrullinated peptide antibody. Subcutaneous MTX was initiated at 10-15 mg per week with further dose escalation up to 20-30 mg per week. Therapy was adjusted every 3 months. If MTX monotherapy did not allow to achieve treatment target of remission or low disease activity, biologics were added.Results:Median DAS 28 at baseline was 5,31 [4,79; 6,14]. Initiation of treatment resulted in steady decrease of disease activity (p<0.05, table1). After 1 year of follow-up 33.8% of patients received MTX monotherapy, 33.8% – MTX in combination with tumor necrosis factor alpha inhibitors, 22.0% – MTX +abatacept, 0.55% – MTX+ tocilizumab, 0.47% – MTX + rituximab. Low disease activity was achieved in 16.3% patients, and remission - in 45.8%. After 6 years median age of patients was 58 [49; 66] years, disease duration – 84 [79; 89] months, low disease activity was documented in 21.3%, and remission – in 7.8% of cases (fig. 1). 7% of patients were able to maintain remission without any treatment. Biologics were discontinued in 15 patients after achieving remission or low disease activity, and synthetic DMARDs – in 5 patients having remission.Conclusion:Intensive therapy initiated at RA onset demonstrates high effectiveness, allowing 61.5% of patients to achieve low disease activity or remission within 12 months, and to maintain these results after 6 years of treatment in 29.2%. Adherence to this strategy allowed to discontinue biologics in 15 patients and synthetic DMARDs in 5 patients after achieving treatment target.Figure 1.Changes of the disease activity during follow-upTable 1.Changes of the main inflammatory activity measures, Me [25th; 75th percentile]Parametres012 months6 yearsDAS285,31 [4,79; 6,14]2,85 [2; 3,90] *4,008 [3,4; 4,59] *SDAI28,27 [18,79; 40,73]5,67 [2; 11,98] *15,06 [9,32; 21] *CDAI25 [17; 36]5 [1,7; 11] *15 [9; 21] *ESR (mm/hr)32 [19; 50]16 [8; 30] *16 [10; 25] *CRP (mg/l)26,55 [6,4; 45,30]3,85 [1,5; 11,3]*2,2 [0,9; 4,9] ** p<0.05 in all cases.Disclosure of Interests:None declared


1992 ◽  
Vol 2 (2) ◽  
pp. 43-46
Author(s):  
U. Fusco ◽  
R. Capelli ◽  
A. Avai ◽  
M. Gerundini ◽  
L. Colombini ◽  
...  

Between 1980 and 1987 we have implanted 46 isoelastic cementless THR in 40 patients affected with rheumatoid arthritis. We have reviewed 38 hips clinically and by X-ray. The mean follow-up was 8,5 years. Harris hip scores ranged from 30.6 preoperatively to 73,4 post-operatively when reviewed. While on the other hand Merle D'Aubigné hip scores ranged from 7,06 pre-operatively to 15,59 post-operatively. All patients have been satisfied, and X-rays showed an improvement for both Charnely and Gruen X-ray score.


2020 ◽  
Vol 47 (10) ◽  
pp. 1464-1474 ◽  
Author(s):  
Dimitrios A. Pappas ◽  
Carol J. Etzel ◽  
Margaux Crabtree ◽  
Taylor Blachley ◽  
Jennie Best ◽  
...  

ObjectiveComorbidity burden and obesity may affect treatment response in patients with rheumatoid arthritis (RA). Few real-world studies have evaluated the effect of comorbidity burden or obesity on the effectiveness of tocilizumab (TCZ). This study evaluated TCZ effectiveness in treating RA patients with high versus low comorbidity burden and obesity versus nonobesity in US clinical practice.MethodsPatients in the Corrona RA registry who initiated TCZ were stratified by low or high comorbidity burden using a modified Charlson Comorbidity Index (mCCI) and by obese or nonobese status using body mass index (BMI). Improvements in disease activity and functionality after TCZ initiation were compared for the above strata of patients at 6 and 12 months after adjusting for statistically significant differences in baseline characteristics.ResultsWe identified patients with high (mCCI ≥ 2; n = 195) and low (mCCI < 2; n = 575) comorbidity burden and patients categorized as obese (BMI ≥ 30; n = 356) and nonobese (BMI < 30; n = 449) who were treated with TCZ. Most patients (> 95%) were biologic experienced and about one-third of patients received TCZ as monotherapy, with no significant differences between patients by comorbidity burden or obesity status. Improvement in disease activity and functionality at 6 and 12 months was similar between groups, regardless of comorbidity burden or obesity status.ConclusionIn this real-world analysis, TCZ was frequently used to treat patients with high comorbidity burden or obesity. Effectiveness of TCZ did not differ by comorbidity or obesity status.


2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Irini Genitsaridi ◽  
Irini Flouri ◽  
Dimitris Plexousakis ◽  
Konstantinos Marias ◽  
Kyriaki Boki ◽  
...  

Abstract Background The long-term outcome of rheumatoid arthritis (RA) patients who in clinical practice exhibit persistent moderate disease activity (pMDA) despite treatment with biologics has not been adequately studied. Herein, we analyzed the 5-year outcome of the pMDA group and assessed for within-group heterogeneity. Methods We included longitudinally monitored RA patients from the Hellenic Registry of Biologic Therapies with persistent (cumulative time ≥ 50% of a 5-year period) moderate (pMDA, 3.2 < DAS28 ≤ 5.1) or remission/low (pRLDA, DAS28 ≤ 3.2) disease activity. The former was further classified into persistent lower-moderate (plMDA, DAS28 < 4.2) and higher-moderate (phMDA, DAS28 ≥ 4.2) subgroups. Five-year trajectories of functionality (HAQ) were the primary outcome in comparing pRLDA versus pMDA and assessing heterogeneity within the pMDA subgroups through multivariable mixed-effect regression. We further compared serious adverse events (SAEs) occurrence between the two groups. Results We identified 295 patients with pMDA and 90 patients with pRLDA, the former group comprising of plMDA (n = 133, 45%) and phMDA (n = 162, 55%). pMDA was associated with worse 5-year functionality trajectory than pRLDA (+ 0.27 HAQ units, CI 95% + 0.22 to + 0.33; p < 0.0001), while the phMDA subgroup had worse 5-year functionality than plMDA (+ 0.26 HAQ units, CI 95% 0.18 to 0.36; p < 0.0001). Importantly, higher persistent disease activity was associated with more SAEs [pRLDA: 0.2 ± 0.48 vs pMDA: 0.5 ± 0.96, p = 0.006; plMDA: 0.32 ± 0.6 vs phMDA: 0.64 ± 1.16, p = 0.038]. Male gender (p = 0.017), lower baseline DAS28 (p < 0.001), HAQ improvement > 0.22 (p = 0.029), and lower average DAS28 during the first trimester since treatment initiation (p = 0.001) independently predicted grouping into pRLDA. Conclusions In clinical practice, RA patients with pMDA while on bDMARDs have adverse long-term outcomes compared to lower disease activity status, while heterogeneity exists within the pMDA group in terms of 5-year functionality and SAEs. Targeted studies to better characterize pMDA subgroups are needed, in order to assist clinicians in tailoring treatments.


2021 ◽  
Author(s):  
Naoki Iwamoto ◽  
Shuntaro Sato ◽  
Shota Kurushima ◽  
Toru Michitsuji ◽  
Shinya Nishihata ◽  
...  

Abstract Objective: To compare the efficacy and safety of tofacitinib and baricitinib in patients with RA in a real-world setting.Methods: A total of 242 patients with RA who were treated with tofacitinib (n=161) or baricitinib (n=81) were enrolled. To avoid confounding, we performed propensity score matching based on multiple baseline characteristic variables, and then 80 baricitinib-treated patients and 57 tofacitinib-treated patients were extracted for direct comparison. Their clinical disease activity and AEs were evaluated for 24 weeks. Results: The mean DAS28-ESR change from baseline to 24 weeks were 1.60 (tofacitinib) and 1.46 (baricitinib). There was no significant difference in the clinical response between two groups. The efficacy was not significantly changed in the patients without concomitant MTX use in both groups, but the concomitant MTX use showed better clinical efficacy in the cases of baricitinib treatment. In both groups, the most common AE was herpes zoster infection, and the AE rates were similar between the two groups. However, the predictive factors contributing to clinical response as revealed by a multivariable logistic analysis differed. The concomitant oral steroid use was independently associated with the achievement of DAS-low disease activity in both groups, whereas in the baricitinib group, the number of biological and/or targeted synthetic DMARDs previously used was also associated. Conclusions: Our findings indicate that tofacitinib and baricitinib had comparable continuing efficacies and safety profiles. However, the influence of clinical characteristics on the treatment response differed. Direct comparison provides useful information to optimal use of JAK inhibitors in real-world settings.


2020 ◽  
Vol 4 (1) ◽  
Author(s):  
Proton Rahman ◽  
Philip Baer ◽  
Ed Keystone ◽  
Denis Choquette ◽  
Carter Thorne ◽  
...  

Abstract Background Long-term clinical registries are essential tools to evaluate new therapies in a patient population that differs from those in randomized clinical trials. The objectives are to describe the profile of rheumatoid arthritis (RA) patients treated with anti-TNF agents in Canadian routine care. Methods RA patients eligible for treatment with Infliximab (IFX), golimumab (GLM) or intravenous golimumab (GLM-IV) as per their respective Canadian product monographs were enrolled into the BioTRAC registry between 2002 and 2017. Study visits occurred at baseline and every 6 months thereafter. Effectiveness was assessed by changes in disease activity. Safety was evaluated by the incidence of adverse events (AEs) and drug survival. Results Of the 890 IFX-, 530 GLM- and 157 GLM-IV-treated patients, the proportion of females ranged from 77.0–86.6%, the mean ages from 55.8–57.7 and the mean disease duration from 6.5–8.6 years. A significant decrease in baseline disease duration and disease activity parameters (DAS, TJC, SJC, HAQ, AM stiffness, MDGA, PtGA, CRP, ESR) was observed over time. Treatment with IFX, GLM- and GLM-IV significantly improved all disease parameters over time. The incidence of AEs was 105, 113 and 82.6 /100 PYs and the incidence of SAEs was 11.7, 11.2 and 4.68 /100 PYs for IFX, GLM- and GLM-IV-treated patients, respectively. Conclusion Differences in baseline characteristics between patients treated with an anti-TNFs over time shows the evolution of treatment modalities over time. All treatments significantly reduced disease activity and improved functionality in a similar fashion. The incidence of adverse events was consistent with the safety profiles of IFX and GLM. Trial registration ClinicalTrials.gov Identifier: NCT00741793 (Retrospectively registered on August 26, 2008).


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