BACKGROUND: In a clinical trial setting, patients with rheumatoid arthritis (RA) taking the Janus kinase inhibitor (JAKi) tofacitinib demonstrated higher adverse events rates compared with those taking the tumour necrosis factor inhibitors (TNFi) adalimumab or etanercept. OBJECTIVE: Compare treatment discontinuations for adverse events (AEs) among second-line therapies in an international real-world RA population. METHODS: Patients initiating JAKi, TNFi or a biological with another mode of action (OMA) from 17 registers participating in the 'JAK-pot' collaboration were included. The primary outcome was the rate of treatment discontinuation due to AEs. We used unadjusted and adjusted cause-specific Cox proportional hazard models to compare treatment discontinuations for AEs among treatment groups by class, but also evaluating separately the specific type of JAKi. RESULTS: Of the 46 913 treatment courses included, 12 523 were JAKi (43% baricitinib, 40% tofacitinib, 15% upadacitinib, 2% filgotinib), 23 391 TNFi and 10 999 OMA. The adjusted cause-specific hazard rate of treatment discontinuation for AEs was similar for TNFi versus JAKi (1.00, 95% CI 0.92 to 1.10) and higher for OMA versus JAKi (1.11, 95% CI 1.01 to 1.23), lower with TNFi compared with tofacitinib (0.81, 95% CI 0.71 to 0.90), but higher for TNFi versus baricitinib (1.15, 95% CI 1.01 to 1.30) and lower for TNFi versus JAKi in patients 65 or older with at least one cardiovascular risk factor (0.79, 95% CI 0.65 to 0.97). CONCLUSION: While JAKi overall were not associated with more treatment discontinuations for AEs, subgroup analyses suggest varying patterns with specific JAKi, such as tofacitinib, compared with TNFi. However, these observations should be interpreted cautiously, given the observational study design.
- MeSH
- antirevmatika * terapeutické užití MeSH
- azetidiny * MeSH
- inhibitory Janus kinas * terapeutické užití MeSH
- inhibitory TNF terapeutické užití MeSH
- lidé MeSH
- puriny * MeSH
- pyrazoly * MeSH
- revmatoidní artritida * farmakoterapie MeSH
- sulfonamidy * MeSH
- TNF-alfa MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
OBJECTIVES: In bio-naïve patients with PsA initiating a TNF inhibitor (TNFi), we aimed to identify baseline predictors of Disease Activity index for PsA in 28 joints (DAPSA28) remission (primary objective) and DAPSA28 moderate response at 6 months, as well as drug retention at 12 months across 13 European registries. METHODS: Baseline demographic and clinical characteristics were retrieved and the three outcomes investigated per registry and in pooled data, using logistic regression analyses on multiply imputed data. In the pooled cohort, selected predictors that were either consistently positive or negative across all three outcomes were defined as common predictors. RESULTS: In the pooled cohort (n = 13 369), 6-month proportions of remission, moderate response and 12-month drug retention were 25%, 34% and 63% in patients with available data (n = 6954, n = 5275 and n = 13 369, respectively). Five common baseline predictors of remission, moderate response and 12-month drug retention were identified across all three outcomes. The odds ratios (95% CIs) for DAPSA28 remission were: age, per year: 0.97 (0.96-0.98); disease duration, years (<2 years as reference): 2-3 years: 1.20 (0.89-1.60), 4-9 years: 1.42 (1.09-1.84), ≥10 years: 1.66 (1.26-2.20); men vs women: 1.85 (1.54-2.23); CRP of >10 vs ≤10 mg/l: 1.52 (1.22-1.89) and 1 mm increase in patient fatigue score: 0.99 (0.98-0.99). CONCLUSION: Baseline predictors of remission, response and adherence to TNFi therapy were identified, of which five were common for all three outcomes, indicating that the predictors emerging from our pooled cohort may be considered generalizable from country level to disease level.
- MeSH
- imunoterapie MeSH
- inhibitory TNF terapeutické užití MeSH
- lidé MeSH
- psoriatická artritida * farmakoterapie MeSH
- registrace MeSH
- únava MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVES: The expanded therapeutic arsenal in rheumatoid arthritis (RA) raises new clinical questions. The objective of this study is to compare the effectiveness of cycling Janus kinase inhibitors (JAKi) with switching to biologic disease-modifying antirheumatic drug (bDMARD) in patients with RA after failure to the first JAKi. METHODS: This is a nested cohort study within data pooled from an international collaboration of 17 national registries (JAK-pot collaboration). Data from patients with RA with JAKi treatment failure and who were subsequently treated with either a second JAKi or with a bDMARD were prospectively collected. Differences in drug retention rates after second treatment initiation were assessed by log-rank test and Cox regression analysis adjusting for potential confounders. Change in Clinical Disease Activity Index (CDAI) over time was estimated using a linear regression model, adjusting for confounders. RESULTS: 365 cycling and 1635 switching patients were studied. Cyclers were older and received a higher number of previous bDMARDs. Both strategies showed similar observed retention rates after 2 years of follow-up. However, adjusted analysis revealed that cycling was associated with higher retention (p=0.04). Among cyclers, when the first JAKi was discontinued due to an adverse event (AE), it was more likely that the second JAKi would also be stopped due to an AE. Improvement in CDAI over time was similar in both strategies. CONCLUSIONS: After failing the first JAKi, cycling JAKi and switching to a bDMARD appear to have similar effectiveness. Caution is advised if an AE was the reason to stop the first JAKi.
BACKGROUND: JAK-inhibitors (JAKi), recently approved in rheumatoid arthritis (RA), have changed the landscape of treatment choices. We aimed to compare the effectiveness of four current second-line therapies of RA with different modes of action, since JAKi approval, in an international collaboration of 19 registers. METHODS: In this observational cohort study, patients initiating tumour necrosis factor inhibitors (TNFi), interleukin-6 inhibitors (IL-6i), abatacept (ABA) or JAKi were included. We compared the effectiveness of these treatments in terms of drug discontinuation and Clinical Disease Activity Index (CDAI) response rates at 1 year. Analyses were adjusted for patient, disease and treatment characteristics, including lines of therapy and accounted for competing risk. RESULTS: We included 31 846 treatment courses: 17 522 TNFi, 2775 ABA, 3863 IL-6i and 7686 JAKi. Adjusted analyses of overall discontinuation were similar across all treatments. The main single reason of stopping treatment was ineffectiveness. Compared with TNFi, JAKi were less often discontinued for ineffectiveness (adjusted HR (aHR) 0.75, 95% CI 0.67 to 0.83), as was IL-6i (aHR 0.76, 95% CI 0.67 to 0.85) and more often for adverse events (aHR 1.16, 95% CI 1.03 to 1.33). Adjusted CDAI response rates at 1 year were similar between TNFi, JAKi and IL-6i and slightly lower for ABA. CONCLUSION: The adjusted overall drug discontinuation and 1 year response rates of JAKi and IL-6i were similar to those observed with TNFi. Compared with TNFi, JAKi were more often discontinued for adverse events and less for ineffectiveness, as were IL-6i.
- MeSH
- abatacept terapeutické užití MeSH
- antirevmatika * terapeutické užití MeSH
- inhibitory Janus kinas * terapeutické užití MeSH
- inhibitory TNF MeSH
- interleukin-6 MeSH
- lidé MeSH
- revmatoidní artritida * chemicky indukované farmakoterapie MeSH
- TNF-alfa MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
OBJECTIVES: RF and ACPA are used as diagnostic tools and their presence has been associated with clinical response to some biologic DMARDs (bDMARDs) in RA. This study compared the impact of seropositivity on drug discontinuation and effectiveness of bDMARDs in patients with RA, using head-to-head comparisons in a real-world setting. METHODS: We conducted a pooled analysis of 16 observational RA registries. Inclusion criteria were a diagnosis of RA, initiation of treatment with rituximab (RTX), abatacept (ABA), tocilizumab (TCZ) or TNF inhibitors (TNFis) and available information on RF and/or ACPA status. Drug discontinuation was analysed using Cox regression, including drug, seropositivity, their interaction, adjusting for concomitant and past treatments and patient and disease characteristics and accounting for country and calendar year of bDMARD initiation. Effectiveness was analysed using the Clinical Disease Activity Index evolution over time. RESULTS: Among the 27 583 eligible patients, the association of seropositivity with drug discontinuation differed across bDMARDs (P for interaction <0.001). The adjusted hazard ratios for seropositive compared with seronegative patients were 1.01 (95% CI 0.95, 1.07) for TNFis, 0.89 (0.78, 1.02)] for TCZ, 0.80 (0.72, 0.88) for ABA and 0.70 (0.59, 0.84) for RTX. Adjusted differences in remission and low disease activity rates between seropositive and seronegative patients followed the same pattern, with no difference in TNFis, a small difference in TCZ, a larger difference in ABA and the largest difference in RTX (Lundex remission difference +5.9%, low disease activity difference +11.6%). CONCLUSION: Seropositivity was associated with increased effectiveness of non-TNFi bDMARDs, especially RTX and ABA, but not TNFis.
- MeSH
- antirevmatika * klasifikace imunologie terapeutické užití MeSH
- biologické přípravky * klasifikace imunologie terapeutické užití MeSH
- lékové interakce imunologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mezinárodní spolupráce MeSH
- monitorování imunologické * metody statistika a číselné údaje MeSH
- nenasazení léčby statistika a číselné údaje MeSH
- posouzení stavu pacienta MeSH
- registrace statistika a číselné údaje MeSH
- revmatoidní artritida * diagnóza farmakoterapie epidemiologie imunologie MeSH
- revmatoidní faktor krev MeSH
- trvání terapie MeSH
- výběr pacientů MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
OBJECTIVES: To compare treatment effectiveness in rheumatoid arthritis (RA) patients naïve to biological disease-modifying antirheumatic drugs (bDMARDs) treated with tocilizumab (TCZ) or TNF-inhibitor (TNFi) with (-combo) or without (-mono) conventional synthetic DMARDs (csDMARDs). METHODS: Patients with RA across 7 European registries, naïve to bDMARDs who initiated treatment with TCZ or TNFi from 2009 to 2016 were included. Drug retention rate was analyzed using Kaplan-Meier and Cox models, and CDAI over time by mixed models. The proportions of patients reaching CDAI low disease activity (LDA) and remission after one year were corrected for attrition. RESULTS: 6713 TNFi-combo, 3762 TNFi-mono, 646 TCZ-combo and 384 TCZ-mono were eligible. Crude median retention was 3.67 years (95%CI 3.41-3.83) for TNFi-combo, 4.14 (3.77-4.62) for TNFi-mono, 2.98 (2.76-3.34) for TCZ-combo and 3.63 years (3.34-5.03) for TCZ-mono. After adjustment for covariates, country and year of treatment initiation stratification, hazards of discontinuation were lower for TCZ-mono (0.60, 95% CI 0.52-0.69) and TCZ-combo (0.66, 95% CI 0.54-0.81) compared to TNFi-combo. Adjusted CDAI evolution was not significantly different between groups. CDAI LDA and remission corrected for attrition were similar between TCZ with or without csDMARDs and TNFi-combo. CONCLUSION: In routine care across 7 European countries, the adjusted drug retention, adjusted CDAI over time and attrition-corrected response proportion for RA patients were similar for bio-naïve patients if treated with TNFi-combo, TCZ-combo or TCZ-mono.
- MeSH
- antirevmatika terapeutické užití MeSH
- dospělí MeSH
- humanizované monoklonální protilátky terapeutické užití MeSH
- inhibitory TNF terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- registrace MeSH
- revmatoidní artritida farmakoterapie MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Geografické názvy
- Evropa MeSH
OBJECTIVE: To compare the effectiveness of tocilizumab (TCZ) and tumour necrosis factor (TNF) inhibitors (TNFi) as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA) after the use of at least one biologic DMARD (bDMARD). METHODS: We included patients with RA having used at least one bDMARD from 10 European registries. We compared drug retention using Kaplan-Meier and Cox models and Clinical Disease Activity Index (CDAI) change over time with mixed-effects models for longitudinal data. The proportions of CDAI remission and low disease activity (LDA) at 1 year were compared using LUNDEX correction. RESULTS: 771 patients on TCZ as monotherapy (TCZ mono), 1773 in combination therapy (TCZ combo), 1404 on TNFi as monotherapy (TNFi mono) and 4660 in combination therapy (TNFi combo) were retrieved. Crude median retention was higher for TCZ mono (2.31 years, 95% CI 2.07 to 2.61) and TCZ combo (1.98 years, 95% CI 1.83 to 2.11) than TNFi combo (1.37 years, 95% CI 1.30 to 1.45) and TNFi mono (1.31 years, 95% CI 1.18 to 1.47). In a country and year of treatment initiation-stratified, covariate-adjusted analysis, hazards of discontinuation were significantly lower among patients on TCZ mono or combo compared with patients on TNFi mono or combo, and TNFi combo compared with TNFi mono, but similar between TCZ mono and combo. Average adjusted CDAI change was similar between groups. CDAI remission and LDA rates were comparable between groups. CONCLUSION: With significantly longer drug retention and similar efficacy to TNFi combo, TCZ mono or combo are reasonable therapeutic options in patients with inadequate response to at least one bDMARD.
- MeSH
- antirevmatika terapeutické užití MeSH
- dospělí MeSH
- humanizované monoklonální protilátky terapeutické užití MeSH
- Kaplanův-Meierův odhad MeSH
- kombinovaná farmakoterapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- proporcionální rizikové modely MeSH
- registrace MeSH
- revmatoidní artritida farmakoterapie MeSH
- senioři MeSH
- stupeň závažnosti nemoci MeSH
- TNF-alfa antagonisté a inhibitory MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
OBJECTIVES: To examine the effectiveness of tocilizumab (TCZ) with and without synthetic disease-modifying antirheumatic drugs (sDMARDs) in a large observational study. METHODS: Patients with rheumatoid arthritis treated with TCZ who had a baseline visit and information on concomitant sDMARDs were included. According to baseline data, patients were considered as taking TCZ as monotherapy or combination with sDMARDs. Main study outcomes were the change of Clinical Disease Activity Index (CDAI) and TCZ retention. The prescription of TCZ as monotherapy was analysed using logistic regression. CDAI change was analysed with a mixed-effects model for longitudinal data. TCZ retention was analysed with a stratified extended Cox model. RESULTS: Multiple-adjusted analysis suggests that prescription of TCZ as monotherapy varied according to age, corticosteroid use, country of the registry and year of treatment initiation. The change of disease activity assessed by CDAI as well as the likelihood to be in remission were not significantly different whether TCZ was used as monotherapy or in combination with sDMARDs in a covariate-adjusted analysis. Estimates for unadjusted median TCZ retention were 2.3 years (95% CI 1.8 to 2.7) for monotherapy and 3.7 years (lower 95% CI limit 3.1, upper limit not estimable) for combination therapies. In a covariate-adjusted analysis, TCZ retention was also reduced when used as monotherapy, with an increasing difference between mono and combination therapy over time after 1.5 years (p=0.002). CONCLUSIONS: TCZ with or without concomitant sDMARDs resulted in comparable clinical response as assessed by CDAI change, but TCZ retention was shorter under monotherapy of TCZ.
- MeSH
- antirevmatika terapeutické užití MeSH
- humanizované monoklonální protilátky terapeutické užití MeSH
- kombinovaná farmakoterapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- revmatoidní artritida farmakoterapie MeSH
- stupeň závažnosti nemoci MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Evropa MeSH
OBJECTIVE: To compare the effectiveness of biologics after rituximab (RTX) treatment in RA. METHODS: The effectiveness of TNF-α inhibitors (TNFi), abatacept (ABA) or tocilizumab (TCZ) was examined in patients previously treated with RTX using clinical data collected in the Collaborative Registries for the Evaluation of Rituximab in RA Collaborative registry. Patients had stopped RTX 6 months or less prior to the new biologic and had a baseline visit within 21 days of starting the new biologic. RESULTS: Two hundred and sixty-five patients were analysed after 6 months of treatment. Patients on TCZ (n = 86) had a greater decline of DAS28-ESR and clinical disease activity index than patients on TNFi (n = 89) or ABA (n = 90). This effect was also seen after adjusting for baseline prednisone use and the number of previous biologics. The mean DAS28-ESR scores in patients on TCZ were 1.0 (95% CI: 0.2, 1.7) and 1.8 (95% CI: 1.0, 2.5) points lower than in patients on TNFi or ABA, respectively. In patients on TCZ, the clinical disease activity index was 9.4 (95% CI: 1.7, 16.1) and 8.1 (95% CI: 0.9, 15.3) points lower than on TNFi and ABA, respectively. Patients on TCZ more frequently had good EULAR responses than patients on TNFi or ABA (66 vs 31 vs 14%, P < 0.001). The HAQ disability index improved in all treatment groups (P < 0.001), but did not differ between biologics, as did drug retention rates. The reasons for discontinuation of RTX and the number of previous biologics had no influence on outcomes. CONCLUSION: In this observational cohort of patients who discontinued RTX, TCZ provided a better control of RA than ABA or TNFi.
- MeSH
- antirevmatika terapeutické užití MeSH
- časové faktory MeSH
- lidé středního věku MeSH
- lidé MeSH
- následné studie MeSH
- progrese nemoci MeSH
- prospektivní studie MeSH
- registrace * MeSH
- revmatoidní artritida farmakoterapie MeSH
- rituximab terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- pozorovací studie MeSH
- Geografické názvy
- Evropa MeSH
BACKGROUND: The approved dose of rituximab (RTX) in rheumatoid arthritis is 1000 mg × 2, but some data have suggested similar clinical efficacy with 500 mg × 2. The purpose of this study was to compare the effectiveness of the regular and low doses given as first treatment course. METHODS: Twelve European registries participating in the CERERRA collaboration (The European Collaborative Registries for the Evaluation of Rituximab in Rheumatoid Arthritis) submitted anonymized datasets with demographic, efficacy and treatment data for patients who had started RTX. Treatment effectiveness was assessed by DAS28 reductions and EULAR responses after 6 months. RESULTS: Data on RTX dose were available for 2,873 patients, of whom 2,625 (91.4 %) and 248 (8.6 %) received 1000 mg × 2 and 500 mg × 2, respectively. Patients treated with 500 mg × 2 were significantly older, had longer disease duration, higher number of prior DMARDs, but lower number of prior biologics and lower baseline DAS28 than those treated with 1000 mg × 2. Fewer patients in the low-dose group received concomitant DMARDs but more frequently received concomitant corticosteroids. Both doses led to significant clinical improvements at 6 months. DAS28 reductions at 6 months were comparable in the 2 dose regimens [mean DeltaDAS28 ± SD -2.0 ± 1.3 (high dose) vs. -1.7 ± 1.4 (low dose), p = 0.23 adjusted for baseline differences]. Similar percentages of patients achieved EULAR good response in the two dose groups, 18.4 % vs. 17.3 %, respectively (p = 0.36). CONCLUSIONS: In this large observational cohort initial treatment with RTX at 500 mg × 2 and 1000 mg × 2 led to comparable clinical outcomes at 6 months.
- MeSH
- antirevmatika aplikace a dávkování MeSH
- databáze faktografické * MeSH
- dospělí MeSH
- internacionalita * MeSH
- kohortové studie MeSH
- kooperační chování * MeSH
- lidé středního věku MeSH
- lidé MeSH
- registrace MeSH
- revmatoidní artritida diagnóza farmakoterapie epidemiologie MeSH
- rituximab aplikace a dávkování MeSH
- senioři MeSH
- statistika jako téma metody MeSH
- výsledek terapie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- Geografické názvy
- Evropa epidemiologie MeSH
