European League Against Rheumatism Response Rate Research Articles

Impact of Single-Nucleotide Polymorphisms of CTLA-4, CD80 and CD86 on the Effectiveness of Abatacept in Patients with Rheumatoid Arthritis.

Abatacept (ABA) is used as a first-line treatment in patients diagnosed with moderate and severe rheumatoid arthritis (RA). The interindividual response to ABA therapy is very variable in these patients. The objective of our study was therefore to investigate the role of polymorphisms of the CTLA-4, CD80 and CD86 genes, as well as that of clinical factors of the disease, in the response to ABA in patients with RA. A retrospective cohort study was carried out in 109 patients receiving treatment with ABA and diagnosed with RA. The genetic variables were analyzed using real-time PCR with TaqMan® probes. The patients were classified according to the European League Against Rheumatism (EULAR) criteria at 6 and 12 months from start of treatment. The independent variables associated with higher EULAR response were lower duration of previous biologic disease-modifying anti-rheumatic drugs and lower baseline values of the disease activity score 28 after 6 months of ABA treatment; and lower baseline patient’s visual analogue scale (PVAS) after 12 months. In addition, a significant association was found between duration of ABA treatment, non-administration of concomitant glucocorticoids and lower baseline values of the number of inflamed joints and erythrocyte sedimentation rate clinical variables, with remission of the disease after 6 months’ treatment with ABA. Finally, remission of the disease after 12 months’ treatment with ABA was associated with earlier age at start of ABA therapy and lower number of previous biologic therapies (BTs). The CTLA-4 rs5742909-T allele and the CTLA-4 rs231775-G allele were found to be associated with satisfactory EULAR response and low disease activity (LDA) after 12 months’ treatment with ABA (CTLA-4 rs5742909 T vs. CC; OR = 5.88; CI95% = 1.48–23.29 and OR = 4.75; CI95% = 1.35–17.94, respectively, and CTLA-4 rs231775 G vs. AA, OR = 3.48; CI95% = 1.20–10.09 and OR = 4.68; CI95% = 1.49–17.94, respectively). In conclusion, patients with RA treated with ABA showed better EULAR response and LDA rate when they had the CTLA-4 rs5742909-T or CTLA-4 rs231775-G polymorphisms; furthermore, this remission rate increased in patients that began ABA treatment earlier, those with a lower number of previous BTs and those with a lower PVAS value.

Abatacept retention and clinical outcomes in Austrian patients with rheumatoid arthritis: real-world data from the 2-year ACTION study.

AbataCepT In rOutiNe clinical practice (ACTION; NCT02109666) was a2-year international observational study of patients with moderate to severe rheumatoid arthritis. Baseline characteristics, abatacept retention rates, and clinical outcomes were compared by treatment line in the Austrian cohort of ACTION. Of 100 patients enrolled in Austria, 98 (98.0%) were evaluable: 33/98 (33.7%) biologic naïve and 65/98 (66.3%) with ≥1 prior biologic failure. At baseline, biologic-naïve patients had shorter disease duration and lower concomitant corticosteroid use than biologic-failure patients. Overall crude abatacept retention rate was 60.5% and retention rate was higher in biologic-naïve (65.1%) versus biologic-failure (58.0%) patients. Good/moderate EULAR (European League Against Rheumatism) response rates were 85.7% in biologic-naïve and 100% in biologic-failure patients. In the Austrian cohort of ACTION, overall abatacept retention at 2years was high, with higher retention rates in patients receiving abatacept as an earlier treatment line. Good/moderate EULAR response rate was higher in biologic-failure than in biologic-naïve patients.

Abatacept retention and clinical outcomes in rheumatoid arthritis: real-world data from the German cohort of the ACTION study and a comparison with other participating countries

IntroductionAbataCepT In rOutiNe clinical practice (ACTION; NCT02109666) was an observational study of patients with rheumatoid arthritis who initiated intravenous abatacept in clinical practice. We aimed to compare abatacept retention rates and clinical outcomes in patients from Germany versus other countries.MethodBaseline characteristics, crude retention rates, and clinical outcomes were compared by treatment line in the German cohort at 2 years. In addition, biologic-naïve patients were compared with biologic-naïve patients pooled from other participating countries.ResultsIn the German cohort, 677/680 (99.6%) patients enrolled were evaluable and 171/677 (25.3%) were biologic naïve. At baseline, abatacept monotherapy was received by a similar proportion of biologic-naïve and biologic-failure patients in the German cohort, but by a greater proportion of biologic-naïve patients in German versus other countries cohort (27.5 vs. 12.9%). The overall crude abatacept retention rate at 2 years in the German cohort was 39.9%; retention rate did not differ significantly by treatment line, but among biologic-naïve patients it was lower in Germany than in the other countries cohort (42.1 vs. 58.7%; log-rank test p < 0.001). At 2 years, good/moderate European League Against Rheumatism (EULAR) response rates in biologic-naïve patients were 85.5% in the German and 92.1% in other countries cohort (p = 0.163).ConclusionsIn the German cohort of ACTION, abatacept retention at 2 years was similar in biologic-naïve and biologic-failure patients. Biologic-naïve patients in German cohort had a significantly lower abatacept retention rate and a trend of lower good/moderate EULAR response rate than those in the other countries cohort.Key Points• Analyses of data from national patient cohorts provide insight on local treatment patterns.• In the German cohort of the ACTION study, abatacept retention at 2 years was similar in biologic-naïve and biologic-failure patients.• Biologic-naïve patients from the German cohort had a significantly lower abatacept retention rate and a trend of lower good/moderate EULAR response rate than patients from other countries.• Data from large international studies may not be directly applicable to individual countries.

Concomitant methotrexate has little effect on clinical outcomes of abatacept in rheumatoid arthritis: a propensity score matching analysis.

To compare the clinical outcomes of abatacept between rheumatoid arthritis patients with and without concomitant methotrexate (MTX) treatment in daily clinical practice. A retrospective cohort study was performed using data from a multicentre registry. A total of 176 consecutive rheumatoid arthritis patients treated with abatacept were included. The propensity score based on multiple baseline characteristic variables was calculated, and 41 of 86 patients treated without MTX (MTX(-)) and 41 of 90 patients treated with concomitant MTX (MTX(+)) were statistically extracted and analysed. Clinical outcomes were evaluated and compared between the two groups over a 52-week period. Baseline characteristics were statistically comparable. No significant differences were observed in the following clinical outcomes from baseline throughout the 52-week period: drug retention rate (MTX(-)/MTX(+) 79.1%/80.5%), mean change in disease activity score based on 28 joints (DAS28-CRP) from baseline (- 1.35/- 1.54), low disease activity rate (48.8%/43.9%), clinical remission rate (31.7%/36.6%), moderate European League Against Rheumatism (EULAR) response rate (68.3%/68.3%), and good EULAR response rate (36.6%/41.1%) at 52weeks. In rheumatoid arthritis patients with similar background characteristics undergoing abatacept treatment, concomitant MTX does not seem to affect clinical outcomes. Abatacept would be a suitable treatment option in daily clinical practice in patients with contraindications to MTX. • This is the first study to directly compare the clinical efficacy and safety of abatacept between patients with and without concomitant methotrexate (MTX) treatment in 'real-world' settings using the propensity score matching method. • There were no significant differences in clinical outcomes of abatacept between patients with and without concomitant MTX treatment. • We used data from a large Japanese multicentre registry for biologics in rheumatoid arthritis, thereby decreasing selection bias based on the personal preferences of physicians.

Brief Report: Attenuated Effectiveness of Tumor Necrosis Factor Inhibitors for Anti-Human T Lymphotropic Virus Type I Antibody-Positive Rheumatoid Arthritis.

To evaluate the effectiveness of tumor necrosis factor (TNF) inhibitors for the treatment of human T lymphotropic virus type I (HTLV-I)-positive patients with rheumatoid arthritis (RA) in an area endemic for HTLV-I infection. We conducted an observational study of 585 RA patients in whom TNF inhibitors were newly introduced as a first biologic disease-modifying antirheumatic drug in an area in southwestern Japan that is endemic for HTLV-I infection. Fifty patients (8.5%) were anti-HTLV-I antibody-positive. The ages of the patients in this group were significantly higher at entry compared with the ages of patients who were anti-HTLV-I antibody-negative (n = 535). The median Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR) was 5.21. Among the total group of patients, 82% were anti-citrullinated protein antibody (ACPA)-positive. The persistence rate of TNF inhibitors at 24 weeks was 89%. The median DAS28-ESR was significantly decreased at 24 weeks in each group. The European League Against Rheumatism (EULAR) response rate was significantly better in the anti-HTLV-I antibody-negative patients (P = 0.0277). Multiple regression analysis demonstrated that anti-HTLV-I antibody status was significantly associated with the EULAR response rate and change in the DAS28-ESR and was prominent especially in the ACPA-negative subjects. No patients developed adult T cell leukemia/lymphoma (ATL) or HTLV-I-associated myelopathy (HAM) during the 24-week treatment period. The efficacy of TNF inhibitors may be attenuated in anti-HTLV-I antibody-positive patients with RA. ATL and HAM did not develop when TNF inhibitors were used for 24 weeks, but the long-term risk is not known.

Is current smoking status and its relationship to anti-cyclic citrullinated peptide antibodies a predictor of worse response to biological therapies in rheumatoid arthritis patients?

Objective: To assess the association between smoking, anti-cyclic citrullinated peptide (anti-CCP) antibody status, and clinical efficacy of biological therapies in rheumatoid arthritis (RA) patients.Method: This retrospective clinical practice setting study included 1349 RA patients from the METEOR database (aged >18 years). We collected data on sociodemographics, smoking status (smoker, <10, 10–19, and >20 cigarettes/day; ex-smoker; non-smoker), baseline disease activity parameters and anti-CCP, previous disease-modifying anti-rheumatic drugs (DMARDs), biological therapy, combined therapy (steroids and DMARDs), and follow-up disease activity. Clinical efficacy was assessed by European League Against Rheumatism (EULAR) good/moderate response rates for all aggregated biological therapies, based on both smoking and anti-CCP status.Results: The non-smoking RA patients were more often female at biological therapy initiation than the ex-smokers and smokers (91.1% vs 60.4% and 67.9%, respectively, p < 0.001), and ex-smokers were older than non-smokers and smokers (mean ± sd 56.5 ± 11.1, 53.5 ± 13.3 and 51.3 ± 11.0 years old, respectively; p < 0.001). In total, 845 (62.6%) were non-smokers, 214 (15.9%) ex-smokers, and 290 (21.5%) smokers [daily cigarettes smoked: 148 (11%) <11; 61 (4.5%) 11–20; and 81 (6%) >20]. Anti CCP-antibody status was similar in both groups. Non-smokers showed higher baseline DAS28 than ex-smokers and smokers (5.0 ± 1.5 vs 4.7 ± 1.4 and 4.7 ± 1.4, respectively; p < 0.001) and used more baseline steroids and DMARDs. A higher EULAR response rate was observed in non-smokers than in ex-smokers and smokers (73% vs 65% and 64.1%, respectively; p = 0.004). Drug survival was higher in non-smokers compared to ex-smokers and smokers [57.7 months (46.4–53.8), 38.6 (30.3–46.8), and 50.1 (41.8–58.4); p < 0.001, respectively].Conclusion: In daily clinical practice, non-smokers respond better than smokers to biological therapy, but this does not result in better drug survival.

Real-world predictors of 12–month intravenous abatacept retention in patients with rheumatoid arthritis in the ACTION observational study

IntroductionAn understanding of real-world predictors of abatacept retention is limited. We analysed retention rates and predictors of abatacept retention in biologic-naïve and biologic-failure patients in a 12-month interim analysis of...

Two-year Efficacy of tocilizumab in Patients With Active Rheumatoid Arthritis in Clinical Practice

ObjectivesTo evaluate the efficacy of tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) in clinical practice, retention rates of the drug and predictors of response. MethodsWe performed a descriptive, prospective, longitudinal, open-label study in patients receiving TCZ (8mg/kg/4 weeks) in a clinical practice setting. The clinical responses were evaluated using the European League Against Rheumatism (EULAR) response criteria, and the low activity and remission rates according to the Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) and the Clinical Disease Activity Index (CDAI). ResultsThe EULAR response rate was 86.63% and the DAS28 remission rate was 53.7% after 6 months of treatment; rates of low disease activity were 52.9% on CDAI and 47.1% on DAS28 at month 24.There were no statistically significant differences in EULAR response, rates of low activity and remission on DAS28 between patients receiving TCZ alone and those receiving TCZ in combination therapy, or between patients positive or negative for rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide (anti-CCP) antibodies. The naïve biological therapy patients showed better remission and low activity rates after 6 months of treatment. The retention rate was 61% at month 24. Adverse events were among the most frequent causes of discontinuation. ConclusionsTocilizumab is effective in RA, has a similar efficacy when used alone or in combination with synthetic disease-modifying antirheumatic drugs (DMARDs) and shows high retention rates.

Eficacia a 2 años de tocilizumab en pacientes con artritis reumatoide activa en la práctica clínica habitual

ObjectivesTo evaluate the efficacy of tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) in clinical practice, retention rates of the drug and predictors of response. MethodsWe performed a descriptive, prospective, longitudinal, open-label study in patients receiving TCZ (8mg/kg/4 weeks) in a clinical practice setting. The clinical responses were evaluated using the European League Against Rheumatism (EULAR) response criteria, and the low activity and remission rates according to the Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) and the Clinical Disease Activity Index (CDAI). ResultsThe EULAR response rate was 86.63% and the DAS28 remission rate was 53.7% after 6 months of treatment; rates of low disease activity were 52.9% on CDAI and 47.1% on DAS28 at month 24.There were no statistically significant differences in EULAR response, rates of low activity and remission on DAS28 between patients receiving TCZ alone and those receiving TCZ in combination therapy, or between patients positive or negative for rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide (anti-CCP) antibodies. The naïve biological therapy patients showed better remission and low activity rates after 6 months of treatment. The retention rate was 61% at month 24. Adverse events were among the most frequent causes of discontinuation. ConclusionsTocilizumab is effective in RA, has a similar efficacy when used alone or in combination with synthetic disease-modifying antirheumatic drugs (DMARDs) and shows high retention rates.

SAT0139 The preventive effect of infliximab on progression of occipito-cervical lesion in RA patients

BackgroundRheumatoid arthritis (RA) is a chronic, progressive, and inflammatory disease, resulting severe joint destruction. Recent reports on the treatment of anti-TNF-a agent have shown strong clinical efficacy in preventing destruction...

Anti-Ro/SSA Antibodies Are an Independent Factor Associated with an Insufficient Response to Tumor Necrosis Factor Inhibitors in Patients with Rheumatoid Arthritis

To study the significance of anti-Ro/SSA antibodies (anti-Ro) in the clinical response to tumor necrosis factor (TNF) inhibitors in patients with rheumatoid arthritis (RA). The clinical responses of a cohort of 190 patients with RA who were treated with infliximab, etanercept, or adalimumab (n = 112, 64, and 14, respectively) as the first biologics were examined using the Disease Activity Score in 28 joints (DAS28) at 24 weeks and the discontinuation rate at 56 weeks. The baseline characteristics of responders and the nonresponders were compared. The clinical response was compared between anti-Ro-negative and -positive patients. The factors associated with the inefficiency of TNF inhibitors were estimated with a multivariable logistic regression analysis. The positive rate of anti-Ro was significantly higher in patients with no European League Against Rheumatism (EULAR) response at 24 weeks (OR 3.64, 95% CI 1.45-9.01, p = 0.003). In anti-Ro-positive patients, a moderate or good EULAR response rate was significantly lower with a sustaining higher median DAS28 (p = 0.006), and this difference was greater among infliximab-treated patients. The discontinuation rate for TNF inhibitors due to inefficacy at 56 weeks was also higher in anti-Ro-positive patients (OR 4.68, 95% CI 1.82-11.99, p = 0.0005), and 75% of these patients received infliximab. The presence of anti-Ro was strongly associated with no EULAR response at 24 weeks and a higher discontinuation rate of TNF inhibitors by 56 weeks (OR 5.22, 95% CI 1.75-15.57, p = 0.003 and OR 10.18, 95% CI 2.18-49.56, p = 0.003). The presence of anti-Ro might be related to the lesser clinical response to infliximab compared to other TNF inhibitors, suggesting that the presence of anti-Ro should be considered when choosing the appropriate biologics for patients with RA.