scholarly journals Early Monitoring of Infliximab Serum Trough Levels Predicts Long-Term Therapy Failure in Patients With Axial Spondyloarthritis

2020 ◽  
Author(s):  
Ana Martínez Feito ◽  
Victoria Navarro-Compán ◽  
Borja Hernández-Breijo ◽  
Eva Olariaga-Mérida ◽  
Diana Peiteado ◽  
...  

Abstract Background: The aim of our study is to evaluate whether serum infliximab trough levels (ITL) during the early stages of treatment are predictive of long-term clinical failure in patients with axial spondyloarthritis (axSpA).Methods: Longitudinal observational study involving 81 patients with axSpA recruited from the SpA-Paz cohort and monitored during infliximab therapy. Serum ITL were measured at baseline, week 2 (W2), W6 and W12 of treatment. Disease activity was assessed by the Ankylosing Spondylitis Disease Activity Score (ASDAS) at baseline, W24 and W54, and every 6 months thereafter until therapy failure. Non-clinically important improvement was defined by ΔASDAS<1.1. The association between serum ITL levels at W12 and clinical outcomes (non-improvement at W52, drug survival and drop-out due to secondary inefficacy) was investigated through logistic regression models and Kaplan Meier curves. Receiver operating characteristic (ROC) curves were employed to determine the best cut-off for serum ITL. Results: Out of the 81 patients, 45 (56%) did not achieve clinical improvement at W52. These patients had lower serum ITL at W12 compared to those who improved: ITL [median (IQR)]: 4.1(0.9-8.3) µg/ml vs 7.1(4.3-11.3)µg/ml, respectively; p=0.007). A cut-off of ITL<6.7µg/mL at W12 was significantly associated with: i) not achieving clinical improvement at W52 (OR: 2.3; 95%CI: 1.3-3.9); ii) shorter drug survival (5.0 years (95% CI: 3.8-6.2) vs 7.6 years (95% CI: 4.8-6.9); p=0.04); and iii) higher drop-out rates due to secondary inefficacy (OR: 3.5; 95%CI: 1.2-10.2). Conclusions: Serum ITL<6.7 µg/mL at W12 were associated with long-term clinical failure in patients with axSpA, especially due to secondary inefficacy.

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Rosie Barnett ◽  
Anita McGrogan ◽  
Matthew Young ◽  
Charlotte Cavill ◽  
Mandy Freeth ◽  
...  

Abstract Background/Aims  Axial spondyloarthritis (axSpA) is a chronic rheumatic condition, characterised by inflammatory back pain - often associated with impaired function and mobility, sleep disturbance, fatigue, and reduced quality of life. Despite the vast advances in pharmacological treatments for axSpA over the last few decades, physical activity and rehabilitation remain vital for effective disease management. At the Royal National Hospital for Rheumatic Diseases in Bath (RNHRD), the 2-week inpatient axSpA rehabilitation programme has been integral to axSpA care since the 1970’s. Prior research has demonstrated significant short-term improvements in spinal mobility (BASMI), function (BASFI) and disease activity (BASDAI) following course attendance. However, the long-term outcomes are yet to be evaluated in this unique cohort. Methods  Since the early 1990’s, clinical measures of spinal mobility, function and disease activity have been routinely collected at the RNHRD at all clinical appointments through administration of the BASMI, BASFI and BASDAI, respectively. Dates of attending the axSpA course and standard clinical and treatment follow-up data were also collected. Multiple linear regression models were used to investigate the impact of course attendance on final reported BASMI, BASDAI and BASFI scores (final score=most recent). Length of follow-up was defined as time between first and last recorded BASMI. Results  Of the 203 patients within the Bath SPARC200 cohort, 77.8% (158/203) had attended at least one rehabilitation course throughout follow-up. 70.0% (140/203) of patients were male. The mean duration of follow-up was 13.5 years (range 0-35 years); 28.1% (57/203) of individuals with 20+ years of follow-up. Course attendance (yes versus no) significantly reduced final BASMI score by 0.84 (p = 0.001, 95%CI -1.31 to -0.37) and final BASDAI score by 0.74 (p = 0.018, 95%CI -1.34 to -0.13). Although course attendance reduced final BASFI by 0.45 (95%CI -1.17 to 0.28), this relationship did not reach significance (p = 0.225). Whilst minimally clinically important difference (MCID) is, to our knowledge, yet to be defined for BASMI, MCIDs were achieved long-term for both BASDAI and BASFI - defined by van der Heijde and colleagues in 2016 as 0.7 and 0.4 for BASDAI and BASFI, respectively. Conclusion  These results provide novel evidence to support the integral role of education, physical activity and rehabilitation in the management of axSpA. Future work should investigate additional outcomes of critical importance to patients and clinicians, such as fatigue, quality of life and work productivity. Furthermore, a greater understanding of the factors that confound these outcomes may provide insights into those patients who may most benefit from attending a 2-week rehabilitation course. In addition to facilitating identification of those patients who may require additional clinical support. Disclosure  R. Barnett: None. A. McGrogan: None. M. Young: None. C. Cavill: None. M. Freeth: None. R. Sengupta: Honoraria; Biogen, Celgene, AbbVie, Novartis, MSD. Grants/research support; Novartis, UCB.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 422-423
Author(s):  
Y. Erez ◽  
A. Karakas ◽  
S. B. Kocaer ◽  
T. Yüce İnel ◽  
S. Gulle ◽  
...  

Background:The frequency of comorbidities has increased in spondyloarthritis patients compared to the general population. The effect of comorbidities on tumour necrosis factor alpha inhibitor (TNFi) drug retention and treatment response has not been well evaluated.Objectives:The purpose of this study to assess the impact of comorbidities on the first TNFi drug survival and treatment response in patients with axial spondyloarthritis (axSpA) registered in theTURKBIOdatabase.Methods:In this study, the frequency of comorbidities, disease activity scores at baseline and month 6 and drug retention were recorded in AxSpA patients iniating first TNFi treatment between 2011 and 2019. Kaplan Meier plot and log rank tests were used for drug survival analysis. Cox regression analysis with HR was performed to evaluate the correlation between comorbidities and drug survival.Results:There were 2428 patients with AxSpA (39.3% female) who used their first TNFi during the study period. Among them, a total of 770 (31%) had at least one comorbid disease. Hypertension was the most common comorbidity (9.7%), followed by the affective disorders (8%) and chronic lung disease (5.8%). The baseline characteristics of patients are shown in Table 1.The presence of any comorbidity did not impact the first TNFi retention (Figure 1). When comorbidities were analysed seperately, we found that only history of cerebrovascular event was negatively associated with drug retention rate (HR: 6.9, p:0.008). There was no statistically significant difference in Bath AS Disease Activity Index 50% (BASDAI50) response between patients with and without comorbidity at 6 months. Less axSpA patients with comorbidity achieved a ASDAS score ≤ 2.1 compared to patients without comorbidity at 6 months.Table 1.Baseline Characteristics of PatientsRadiographic Spondyloarthritis, n (%)2318 (95.5)Female, n(%)954 (39.3)Age, year42.2±11.8Age at diagnosis, years32.5± 11.3Age at initial TNFi, years39.4 ± 11.1Symptom duration, years9.7± 7.5Time to initial TNFi, years7±6.8HLA-B27- positivity, n (%)1144 (47.1)Smokers, n (%)1068 (44)Baseline BASDAI35.5±22.2Baseline ASDAS-CRP2.8±1.1Baseline CRP (mg/L)15.7±24.4VAS global patient46.6±28.7-Quantitative variables are presented as mean ± SD, and qualitative variables are presented as frequency and percentage-ASDAS-CRP, Ankylosing Spondylitis Disease Activity Score using C-reactive protein VAS, visual analogue scaleConclusion:The results of this study demonstrated that the presence of previous cerebrovascular event decreased the first TNFi survival in patients with axSpA. It also suggested that comorbidities might decrease TNFi treatment response.Disclosure of Interests:None declared


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 437-437
Author(s):  
D. Poddubnyy ◽  
V. Rios Rodriguez ◽  
M. Torgutalp ◽  
M. Verba ◽  
J. Callhoff ◽  
...  

Background:Previous studies showed that patients with non-radiographic and radiographic axial spondyloarthritis (nr- and r-axSpA) have similar disease burden and similar response to anti-inflammatory therapy given similar level of inflammatory activity. Only little is known, however, about long-term disease course in patients with early axSpA.Objectives:To investigate the long-term (up to 10 years) clinical course of patients with early axSpA.Methods:In total, 525 patients with early axSpA (r-axSpA with symptom duration ≤10 years and nr-axSpA with symptom duration ≤5 years) from the German Spondyloarthritis Inception Cohort (GESPIC) were included. The final patient classification was based on central reading results in 458 patients with available pelvic X-rays, and on local rheumatologist judgement in 67 patients. A total of 251 patients were finally classified as r-axSpA and 274 as nr-axSpA. Clinical evaluation, which included disease activity (BASDAI, C-reactive protein – CRP, ASDAS) as well as therapy recording, was performed at baseline and every 6 months thereafter until year 2 and annually thereafter till year 10. Treatment was conducted at the discretion of the local rheumatologist.Results:Since the cohort has started prior to introduction of TNF inhibitors (TNFi), only 2% patients received TNFi at baseline that increased to 23% at year 10 (15% in nr-axSpA and 31% in r-axSpA) – Figure 1. The use of NSAIDs and csDMARDs decreased in both groups (Figure 1), while use of systemic steroids did not change substantially (9% at baseline, 8% at year 10). The proportion of patients with low disease activity according to BASDAI (<4) was higher in r-axSpA as compared to nr-axSpA at almost all time points, while the proportion of patients with low disease activity according to ASDAS (<2.1), as well as with ASDAS inactive disease (<1.3) was similar between nr-axSpA and r-axSpA (Figure 2). In the group of patients who completed year 10 (n=134 in total, 68 with nr-axSpA, 67 with r-axSpA) the same trends in therapy and disease activity were observed.Conclusion:Patients with nr-axSpA and r-axSpA showed a similar disease course in terms of disease activity on the group level. The drop-out rate in this observational cohort was overall high, but comparable between groups. The lower proportion of patients with nr-axSpA being treated with TNFi might reflect a later introduction of TNFi for this indication.Acknowledgments:GESPIC has been financially supported by the German Federal Ministry of Education and Research as well as by Abbott, Amgen, Centocor, Schering–Plough, and Wyeth. From 2010 till 2019 GESPIC has been supported by Abbvie.Disclosure of Interests:Denis Poddubnyy Grant/research support from: AbbVie, MSD, Novartis, and Pfizer, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB, Valeria Rios Rodriguez Consultant of: Abbvie, Novartis, Murat Torgutalp: None declared, Maryna Verba: None declared, Johanna Callhoff: None declared, Mikhail Protopopov Consultant of: Novartis, Fabian Proft Grant/research support from: Novartis Pharma GmbH, Consultant of: Consultancy / speaker fees from: Abbvie, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, UCB, Speakers bureau: Consultancy / speaker fees from: Abbvie, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, UCB, Judith Rademacher: None declared, Hildrun Haibel Consultant of: Abbvie, Jansen, MSD, and Novartis, Speakers bureau: Abbvie, Jansen, MSD, and Novartis, Joachim Sieper Consultant of: AbbVie, Boehringer Ingelheim, Eli Lilly and Company, Janssen, Merck, Novartis, Pfizer, Roche, and UCB Pharma, Speakers bureau: AbbVie, Boehringer Ingelheim, Eli Lilly and Company, Janssen, Merck, Novartis, Pfizer, Roche, and UCB Pharma, Martin Rudwaleit Consultant of: AbbVie, BMS, Celgene, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB Pharma


1983 ◽  
Vol 50 (04) ◽  
pp. 797-799 ◽  
Author(s):  
L Grodzińska ◽  
M Basista ◽  
A Kȩdzior ◽  
R Korbut ◽  
E Kostka-Trąbka ◽  
...  

SummaryTwenty-one patients with arteriosclerosis obliterans of lower extremities were treated with beta-pyridylcarbinol (Ronicol) for five weeks. The long-term therapy with beta-pyridylcarbinol did not influence platelet aggregability. Activation of the fibrinolytic system was observed. This fibrinolytic effect of Ronicol was abolished in patients treated with aspirin. In most cases a slight clinical improvement was seen, manifested by elongation of pain-free walking distance and increased blood flow in affected limbs. It is concluded that the therapeutic effect of Ronicol in humans may be partly mediated by the release of endogenous prostacyclin.


2001 ◽  
Vol 25 (1) ◽  
pp. 25-31 ◽  
Author(s):  
Franco Cozzi ◽  
Piero Marson ◽  
Mara Rosada ◽  
Giustina De Silvestro ◽  
Arianna Bullo ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document