scholarly journals Effectiveness, Tolerability, and Safety of Tofacitinib in Rheumatoid Arthritis: A Retrospective Analysis of Real-World Data from the St. Gallen and Aarau Cohorts

2019 ◽  
Vol 8 (10) ◽  
pp. 1548 ◽  
Author(s):  
Mueller ◽  
Hasler ◽  
Popp ◽  
Mattow ◽  
Durmisi ◽  
...  

: Introduction: Tofacitinib is an oral JAK inhibitor indicated for the treatment of rheumatoid arthritis (RA). The efficacy and safety of tofacitinib have been shown in several randomized clinical trials. The study presented here aimed to assess the clinical tolerability and effectiveness of tofacitinib among RA patients in real life. Methods: Consecutive patients between January 2015 and April 2017 with RA who fulfilled the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) 2010 criteria were included in a prospectively designed analysis of retrospective data. Patients were initiated on tofacitinib 5 mg bid. The primary objective was to analyze the safety of tofacitinib in a real-life cohort. Safety was assessed by the reasons to stop tofacitinib during follow up and changes of liver enzymes, hemoglobin, and creatinine. The secondary outcome was to analyze the frequency of and time to achieve low disease activity (LDA) and remission as defined by 28 joint count disease activity score (DAS28). Results: A total of 144 patients were treated with tofacitinib. A total of 84.9% of patients were pre-exposed to at least one biological agent. The average DAS28 at the initiation of tofacitinib was 4.43. A total of 50.0% of patients were positive for rheumatoid factor and 49.0% for ACPA. The mean follow up was 1.22 years (range 10d–3.7a) after initiation of tofacitinib treatment. A total of 94 (64.4%) patients remained on tofacitinib during follow-up. The average time to stop tofacitinib was 190.0 days. Reasons to stop tofacitinib were: insufficient response (n = 23), gastrointestinal symptoms (n = 18), infection (n = 5), myalgia (n = 2), remission (n = 2), headache (n = 2), cough, blue finger syndrome, intolerance, heartburn, psoriasis, and increased liver enzymes (all n = 1). Increased alanine amino transferase (ALAT) or aspartate amino transferase (ASAT) > 2× upper limit of normal (ULN) were detected in 3.3% and 4.4% of patients, respectively. Hemoglobin decrease of >10% was detected in 15.1% of the patients and decreased lymphocytes <500/μL in 3.4%. An increase of creatinine >20% was detected in 9.4% of patients. A total of 62.9% and 50.0% of the patients achieved low disease activity (LDA) or remission after a median of 319 and 645 days, respectively. These rates were significantly higher in patients naïve to biologic agents as compared to patients pre-exposed to biologics (LDA: naïve 100% 92 d, pre-exposed 57.0% 434 d, p ≤ 0.001; remission: naïve 86.7% 132 d, pre-exposed 44.1%, 692 d, p = 0.001). Conclusions: Tofacitinib is a safe and effective treatment option for patients with RA. Tofacitinib may induce high rates of LDA and remission in patients with active disease, even after the use of one or more biologics, though the rate appeared higher in patients naïve to biologics. Tofacitinib may be a valuable option in a treat-to-target approach. Our data demonstrate that Janus kinase (JAK) inhibitors are safe and efficacious in real life patients.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1456.1-1457
Author(s):  
D. Iacono ◽  
I. Pantano ◽  
D. Birra ◽  
G. Scalise ◽  
M. A. Coscia ◽  
...  

Background:EULAR recommendations focus the importance of Methotrexate (MTX) therapy as a key element in the treatment of patients with Rheumatoid Arthritis (RA), alone as first line therapy and in combination with biological Disease Modifying Anti-rheumatic Drug (bDMARDs). Abatacept (CTLA4-Ig) in Europe is approved for the treatment of moderate to severe active RA in combination with MTX. Several patients, however, discontinue MTX for intolerance, side effects or contraindications, and real-life data demonstrate how, even in patients receiving therapy with MTX, compliance could be suboptimal. The only data on the use of abatacept in monotherapy come from the ORA-Registry, where a worse performance is observed in monotherapy patients.Objectives:To evaluate a multicenter cohort of RA patients treated with Abatacept in patients underwent combined MTX therapy vs monotherapy.Methods:We retrospectively evaluated RA patients, referring to 2 Italian rheumatology centers, treated with Abatacept monotherapy or in combination with MTX. We compared both persistence in therapy and the rate of remission/low disease activity according to Clinical Disease Activity Index (CDAI) between the 2 groups.Results:We enrolled 147 patients, out of them 66 patients were on monotherapy with Abatacept due to intolerance or controindications and 81 in therapy with Abatacept plus MTX. The two cohorts appeared homogeneous in age, gender, disease duration and baseline activity indexes, with the only difference being higher baseline Physician Global assessment (PhGA) values in monotherapy patients. During the follow-up (median duration 24±14 months), the retention rate of Abatacept treatment was 71.2% in MTX patients (median duration 27–15.6 months) and 62.1% in monotherapy patients (median duration 25.2–17.5; p=ns). No differences between the two groups in terms of retention rate, low-disease activity and CDAI remission (log rank p=ns), Breslow p=ns) were detected.Conclusion:In patients with RA with intolerance or contraindication to MTX use, Abatacept monotherapy could be an efficient and safe option even in the long term follow-up.References:[1]Abatacept monotherapy compared with abatacept plus disease-modifying anti-rheumatic drugs in rheumatoid arthritis patients: data from the ORA registry.Truchetet ME et al. Arthritis Res Ther. 2016 Mar 30;18:72.Disclosure of Interests:DANIELA IACONO Speakers bureau: PFIZER, BRISTOL MAYERS SQUIBB, SANOFI, Ilenia Pantano: None declared, domenico birra: None declared, GIUSEPPE SCALISE: None declared, Melania Alessia Coscia: None declared, VALENTINA MESSINITI: None declared, Gabriella Loi: None declared, Anna Merchionda: None declared, Paolo Moscato: None declared, francesco ciccia Grant/research support from: pfizer, novartis, roche, Consultant of: pfizer, novartis, lilly, abbvie, Speakers bureau: pfizer, novartis, lilly, abbvie


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1154-1155
Author(s):  
L. Cometi ◽  
C. Bruni ◽  
L. Tofani ◽  
G. Tesei ◽  
F. Nacci ◽  
...  

Background:Biologic and target synthetic disease modifying anti-rheumatic drugs (bDMARDs and tcDMARDs) are recommended to control RA disease activity, pain and steroid use. Following randomized clinical trials (RCTs) and their post-hoc analyses, the Janus Kinase Inhibitor tsDMARDs BARI was superior to reference bDMARD Adalimumab in reducing disease activity, pain and functional disability. In addition, BARI monotherapy also determined more significant pain reduction and functional improvement when compared to Tocilizumab monotherapy (3).Objectives:to confirm RCT results in a real-life clinical setting, with focus on disease activity, pain, functional disability and steroid tapering, when comparing BARI to bDMARDs for the treatment of active RA.Methods:RA patients starting BARI or a bDMARD for active RA were retrospectively evaluated from June 2019 to June 2020. Disease activity (DAS28CRP, SDAI, CDAI), pain visual analogic scale (pain_VAS), functional disability (HAQ) assessments and mean prednisone dosage (pred_dose) were collected at baseline (BL), 3 months (3M) and 6 months (6M) after BARI/bDMARD initiation. The changes of the outcome measures were evaluated between BL-3M, 3M-6M and BL-6M, as well as between BARI and bDMARDs groups. Finally, we assessed the variables associated with prednisone tapering in the whole population.Results:90 out of 100 RA patients evaluated (baseline: age 57±12 years, disease duration 131±100 months, DAS28PCR 4.8±1.0, pain_VAS 61±23 mm, prednisone dose 5.5±5.3 mg) were eligible for the study; 49 received BARI and 41 bDMARDs (17 abatacept, 12 TNF inhibitors, 11 tocilizumab, 1 rituximab). At BL, the two groups did not differ statistically in terms of age, sex, disease duration, disease activity, pain_VAS, previous bDMARD failure or ts/bDMARD naive, concomitant conventional synthetic DMARDs treatment, pred_dose. Both BARI and bDMARDs determined a significant reduction in activity scales and HAQ when comparing BL-3M and BL-6M, with only pain_VAS and pred_dose showing a significant decrease in the 3M-6M interval. When comparing the two groups, BARI showed a significantly higher reduction of pred_dose (-3.2±5.1 vs -1.7±3.7 mg at BL-3M, and -4.1±5.3 vs -1.9±4.6 mg at BL-6M), which was not significant after adjusting for BL pred_dose. No other difference was seen when the two groups, including the numerically higher reduction of pain_VAS in the BARI group (-29±28 vs -20±27 mm at BL-3M and -35±25 vs -30±28 mm at BL-6M comparison). The analysis of the predictors for steroid tapering (Δmean_pred) in the two intervals, showed that BL DAS28PCR, DAS28PCR BL-3M change and BL pred_dose were associated with BL-3M Δmean_pred, while 3M pain_VAS and 3M pred_dose were associated with 3M-6M Δmean_pred.Conclusion:Although limited by the small samples and the retrospective nature, our real-life comparison shows similar efficacy of BARI and bDMARDs in terms of disease activity control, functional disability and pain. In addition, the treatment with BARI or bDMARD did not influence the steroid tapering, which was driven mostly by its initial dose, disease activity and pain. Larger real-life multi-center studies are warranted to confirm our results.References:[1]Taylor PC et al. Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis. N Engl J Med. 2017 Feb 16;376(7):652-662.[2]Fautrel B et al. Effect of Baricitinib and Adalimumab in Reducing Pain and Improving Function in Patients with Rheumatoid Arthritis in Low Disease Activity: Exploratory Analyses from RA-BEAM. J Clin Med. 2019 Sep 5;8(9):1394.[3]Fautrel B et al. Comparative effectiveness of improvement in pain and physical function for baricitinib versus adalimumab, tocilizumab and tofacitinib monotherapies in rheumatoid arthritis patients who are naïve to treatment withDisclosure of Interests:Laura Cometi: None declared, Cosimo Bruni Speakers bureau: Actelion, Consultant of: Eli Lilly, Grant/research support from: Fondazione Italiana Ricerca sull’Artrite (FIRA), Gruppo Italiano lotta alla Sclerodermia (GILS), New Horizon Fellowship, European Scleroderma Trials and Research (EUSTAR) group, Foundation for Research in Rheumatology (FOREUM)., Lorenzo Tofani: None declared, Giulia Tesei: None declared, Francesca Nacci: None declared, Ginevra Fiori: None declared, Francesca Bartoli: None declared, Marco Matucci-Cerinic Speakers bureau: Biogen Italia, Actelion, Bayer, Boehringer Ingelheim, CSL Behring, Eli-Lilly, Consultant of: Biogen Italia, Actelion, Bayer, Boehringer Ingelheim, CSL Behring, Eli-Lilly, Grant/research support from: Biogen Italia, Actelion, Bayer, Boehringer Ingelheim, CSL Behring, Eli-Lilly,


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1463.2-1464
Author(s):  
S. Bayat ◽  
K. Tascilar ◽  
V. Kaufmann ◽  
A. Kleyer ◽  
D. Simon ◽  
...  

Background:Recent developments of targeted treatments such as targeted synthetic DMARDs (tsDMARDs) increase the chances of a sustained low disease activity (LDA) or remission state for patients suffering rheumatoid arthritis (RA). tsDMARDs such as baricitinib, an oral inhibitor of the Janus Kinases (JAK1/JAK2) was recently approved for the treatment of RA with an inadequate response to conventional (cDMARD) and biological (bDMARD) therapy. (1, 2).Objectives:Aim of this study is to analyze the effect of baricitinb on disease activity (DAS28, LDA) in patients with RA in real life, to analyze drug persistance and associate these effects with various baseline characteristics.Methods:All RA patients were seen in our outpatient clinic. If a patient was switched to a baricitinib due to medical reasons, these patients were included in our prospective, observational study which started in April 2017. Clinical scores (SJC/TJC 76/78), composite scores (DAS28), PROs (HAQ-DI; RAID; FACIT), safety parameters (not reported in this abstract) as well as laboratory biomarkers were collected at each visit every three months. Linear mixed effects models for repeated measurements were used to analyze the time course of disease activity, patient reported outcomes and laboratory results. We estimated the probabilities of continued baricitinib treatment and the probabilities of LDA and remission by DAS-28 as well as Boolean remission up to one year using survival analysis and explored their association with disease characteristics using multivariable Cox regression. All patients gave informed consent. The study is approved by the local ethics.Results:95 patients were included and 85 analyzed with available follow-up data until November 2019. Demographics are shown in table 1. Mean follow-up duration after starting baricitinib was 49.3 (28.9) weeks. 51 patients (60%) were on monotherapy. Baricitinib survival (95%CI) was 82% (73% to 91%) at one year. Cumulative number (%probability, 95%CI) of patients that attained DAS-28 LDA at least once up to one year was 67 (92%, 80% to 97%) and the number of patients attaining DAS-28 and Boolean remission were 31 (50%, 34% to 61%) and 12(20%, 9% to 30%) respectively. Median time to DAS-28 LDA was 16 weeks (Figure 1). Cox regression analyses did not show any sufficiently precise association of remission or LDA with age, gender, seropositivity, disease duration, concomitant DMARD use and number of previous bDMARDs. Increasing number of previous bDMARDs was associated with poor baricitinib survival (HR=1.5, 95%CI 1.1 to 2.2) while this association was not robust to adjustment for baseline disease activity. Favorable changes were observed in tender and swollen joint counts, pain-VAS, patient and physician disease assessment scores, RAID, FACIT and the acute phase response.Conclusion:In this prospective observational study, we observed high rates of LDA and DAS-28 remission and significant improvements in disease activity and patient reported outcome measurements over time.References:[1]Keystone EC, Taylor PC, Drescher E, Schlichting DE, Beattie SD, Berclaz PY, et al. Safety and efficacy of baricitinib at 24 weeks in patients with rheumatoid arthritis who have had an inadequate response to methotrexate. Annals of the rheumatic diseases. 2015 Feb;74(2):333-40.[2]Genovese MC, Kremer J, Zamani O, Ludivico C, Krogulec M, Xie L, et al. Baricitinib in Patients with Refractory Rheumatoid Arthritis. The New England journal of medicine. 2016 Mar 31;374(13):1243-52.Figure 1.Cumulative probability of low disease activity or remission under treatment with baricitinib.Disclosure of Interests:Sara Bayat Speakers bureau: Novartis, Koray Tascilar: None declared, Veronica Kaufmann: None declared, Arnd Kleyer Consultant of: Lilly, Gilead, Novartis,Abbvie, Speakers bureau: Novartis, Lilly, David Simon Grant/research support from: Else Kröner-Memorial Scholarship, Novartis, Consultant of: Novartis, Lilly, Johannes Knitza Grant/research support from: Research Grant: Novartis, Fabian Hartmann: None declared, Susanne Adam: None declared, Axel Hueber Grant/research support from: Novartis, Lilly, Pfizer, EIT Health, EU-IMI, DFG, Universität Erlangen (EFI), Consultant of: Abbvie, BMS, Celgene, Gilead, GSK, Lilly, Novartis, Speakers bureau: GSK, Lilly, Novartis, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB


2017 ◽  
Vol 33 (S1) ◽  
pp. 59-60
Author(s):  
Jéssica dos Santos ◽  
Haliton Oliveira ◽  
Francisco Acurcio Michael da Silva ◽  
Alessandra Almeida ◽  
Flávia Rodrigues ◽  
...  

INTRODUCTION:Biological disease-modifying anti-rheumatic drugs (bDMARDs) have become firmly established in the management of patients with rheumatoid arthritis (RA), but some patients do not improve despite therapy. This study evaluated the predictors of effectiveness of the bDMARDs on a cohort of patients with rheumatoid arthritis (RA) in the Brazilian Public Health System.METHODS:RA individuals treated with bDMARDs, were included in the open prospective cohort study. The Clinical Disease Activity Index (CDAI) was used to assess the effectiveness comparing results at baseline and after 6 months of follow-up. The association between socio-demographic and clinical characteristics with the disease activity measured by the CDAI was also investigated. The bDMARDs was considered effective when the patient achieved remission or low disease activity and considered not effective when there was still moderate or high disease activity. Pearson's chi-square was applied for the univariate analysis to evaluate the association of effectiveness measured by the CDAI with the socio-demographic (gender, education, marital status and race) and clinical variables (type of drug, EuroQol (EQ)-5D and Health Assessment Questionnaire (HAQ)). Logistic regression was applied in the multivariate analysis of the variables that presented a p< .20 value during the univariate analysis.RESULTS:All 266 RA patients completed six months of follow-up. The most widely used bDMARDs was adalimumab (57.1 percent), with etanercept used by 22.2 percent, golimumab by 7.5 percent, abatacept by 4.5 percent, tocilizumab by 3.4 percent, infliximab by 2.6 percent, certolizumab by 1.5 percent, and rituximab by 1.1 percent. The bDMARDs reduced disease activity as measured by CDAI at six months of follow-up (p<.001). The percentage of patients achieving remission or low disease activity was 40.6 percent. bDMARDs were more effective in patients with better functionality (Odds Ratio, OR = 2.140 / 95 percent Confidence Interval, CI 1.219 - 3.756) at beginning of treatment and in patients who not had a previous bDMARDs (OR = 2.150 / 95 percent CI 1.144 - 4.042).CONCLUSIONS:In this real-world study, functionality and use of previous bDMARDs are predictors in patients with RA treated with bDMARDs.


Author(s):  
Shunsuke Mori ◽  
Yukinori Koga ◽  
Mineharu Sugimoto

We treated 21 patients with organizing pneumonia (OP) associated with rheumatoid arthritis (RA) or related to biological disease-modifying antirheumatic drugs (DMARDs) at our institution between 2006 and 2014. Among these cases, 3 (14.3%) preceded articular symptoms of RA, 4 (19.0%) developed simultaneously with RA onset, and 14 (66.7%) occurred during follow-up periods for RA. In the case of OP preceding RA, increased levels of anti-cyclic citrullinated peptide antibodies and rheumatoid factor were observed at the OP onset. RA disease activity was related to the development of OP in the simultaneous cases. In the cases of OP developing after RA diagnosis, 10 of 14 patients had maintained low disease activity with biological DMARD therapy at the OP onset, and among them, 6 patients developed OP within the first year of this therapy. In the remaining four patients, RA activity was not controlled at the OP onset. All patients responded well to systemic steroid therapy, but two patients suffered from relapses of articular and pulmonary symptoms upon steroid tapering. In most of the RA patients, DMARD therapy was introduced or restarted during the steroid tapering. We successfully restarted a biological DMARD that had not been previously used for patients whose RA would otherwise have been difficult to control. In this study, we also perform a review of the literature on RA-associated or biological DMARD-related OP and discuss the pathogenesis and management of OP occurring in RA patients.


2016 ◽  
Vol 83 (6) ◽  
pp. 721-725 ◽  
Author(s):  
Florenzo Iannone ◽  
Giorgio Carlino ◽  
Antonio Marchesoni ◽  
Piercarlo Sarzi-Puttini ◽  
Roberto Gorla ◽  
...  

RMD Open ◽  
2019 ◽  
Vol 5 (2) ◽  
pp. e000994 ◽  
Author(s):  
Denis Mongin ◽  
Kim Lauper ◽  
Carl Turesson ◽  
Merete Lund Hetland ◽  
Eirik Klami Kristianslund ◽  
...  

ObjectiveTo compare several methods of missing data imputation for function (Health Assessment Questionnaire) and for disease activity (Disease Activity Score-28 and Clinical Disease Activity Index) in rheumatoid arthritis (RA) patients.MethodsOne thousand RA patients from observational cohort studies with complete data for function and disease activity at baseline, 6, 12 and 24 months were selected to conduct a simulation study. Values were deleted at random or following a predicted attrition bias. Three types of imputation were performed: (1) methods imputing forward in time (last observation carried forward; linear forward extrapolation); (2) methods considering data both forward and backward in time (nearest available observation—NAO; linear extrapolation; polynomial extrapolation); and (3) methods using multi-individual models (linear mixed effects cubic regression—LME3; multiple imputation by chained equation—MICE). The performance of each estimation method was assessed using the difference between the mean outcome value, the remission and low disease activity rates after imputation of the missing values and the true value.ResultsWhen imputing missing baseline values, all methods underestimated equally the true value, but LME3 and MICE correctly estimated remission and low disease activity rates. When imputing missing follow-up values at 6, 12, or 24 months, NAO provided the least biassed estimate of the mean disease activity and corresponding remission rate. These results were not affected by the presence of attrition bias.ConclusionWhen imputing function and disease activity in large registers of active RA patients, researchers can consider the use of a simple method such as NAO for missing follow-up data, and the use of mixed-effects regression or multiple imputation for baseline data.


2020 ◽  
Vol 12 ◽  
pp. 1759720X2093713
Author(s):  
Konstantinos Thomas ◽  
Argiro Lazarini ◽  
Evripidis Kaltsonoudis ◽  
Alexandros Drosos ◽  
Ioannis Papalopoulos ◽  
...  

Background: Data regarding the real-life predictors of low disease activity (LDA) in rheumatoid arthritis (RA) patients are limited. Our aim was to evaluate the rate and predictors of LDA and treatment patterns in RA. Methods: This was a multicenter, prospective, RA cohort study where patients were evaluated in two different time points approximately 12 months apart. Statistical analysis was performed in order to identify predictors of LDA while patterns of disease-modifying anti-rheumatic drug [DMARDs; conventional synthetic (csDMARD) or biologic (bDMARD)] and glucocorticoid (GC) use were also recorded. Results: The total number of patients included was 1317 (79% females, mean age: 62.9 years, mean disease duration: 10.3 years). After 1 year, 57% had achieved LDA (DAS28ESR<3.2) while 43% did not (34%: moderate disease activity: DAS28ESR ⩾3.2 to <5.1, 9%: high disease activity, DAS28ESR ⩾5.1). By multivariate analysis, male sex was positively associated with LDA [odds ratio (OR) = 2.29 p < 0.001] whereas advanced age (OR = 0.98, p = 0.005), high Health Assessment Questionnaire (HAQ) score (OR = 0.57, p < 0.001), use of GCs (OR = 0.75, p = 0.037) or ⩾2 bDMARDs (OR = 0.61, p = 0.002), high co-morbidity index (OR = 0.86, p = 0.011) and obesity (OR = 0.62, p = 0.002) were negative predictors of LDA. During follow-up, among active patients (DAS28ESR >3.2), 21% initiated (among csDMARDs users) and 22% switched (among bDMARDs users) their bDMARDs. Conclusion: In a real-life RA cohort, during 1 year of follow-up, 43% of patients do not reach treatment targets while only ~20% of those with active RA started or switched their bDMARDs. Male sex, younger age, lower HAQ, body mass index and co-morbidity index were independent factors associated with LDA while use of GCs or ⩾2 bDMARDs were negative predictors.


Sign in / Sign up

Export Citation Format

Share Document