scholarly journals Early response to anti-TNF predicts long-term outcomes including sustained remission: an analysis of the BSRBR-RA

Rheumatology ◽  
2019 ◽  
Vol 59 (7) ◽  
pp. 1709-1714 ◽  
Author(s):  
Philip D H Hamann ◽  
John D Pauling ◽  
Neil McHugh ◽  
Kimme Hyrich ◽  
Gavin Shaddick ◽  
...  

Abstract Objective To identify different trajectories of disease activity in patients with RA following initiation of a first anti-TNF. Methods Patients with RA starting their first anti-TNF between 2001 and 2013 were selected from the British Society for Rheumatology Biologics Register for RA. Six-monthly DAS28-ESR scores were used to identify trajectories of disease activity using latent class modelling. Data were included for six follow-ups after registration (approximately 3 years). Subgroup analysis examined changes in disease activity profiles over time. Results A total of 14 436 patients with RA starting their first anti-TNF were enrolled between 2001 and 2013 (13 115 between 2001 and 2008, 1321 between 2010 and 2013). The mean number of DAS28-ESR scores was 3.5/patient (s.d. 2.1), with a mean of 184.9 days (s.d. 69.9) between scores. The DAS28-ESR nadir was achieved within 250 days of commencing anti-TNF, although apparent trajectory divergence emerged by first 6-monthly follow-up at 180 days. Four distinct response trajectories comprised the most stable model. Most patients fitted into ‘modest’ (7986 patients; 55.3%) or ‘substantial’ (4676 patients; 32.4%) response trajectories. Of the remainder, 1254 (8.7%) and 520 (3.6%) fitted ‘maximal’ and ‘minimal’ response trajectories, respectively. There was a significant (P < 0.01) increase in proportion achieving ‘maximal’ response between 2001–2008 and 2010–2013. Conclusion This is the largest study to identify long-term response trajectories with anti-TNF. By 6 months, longer-term trajectory profiles of DAS28 could already be identified, with many patients identified earlier. The majority of patients had persistent moderate response, equivalent to maintained DAS28-ESR moderate disease activity. The maximal response trajectory (equivalent to sustained DAS2-ESR remission) was only achieved by approximately one-third of patients.

2011 ◽  
Vol 71 (5) ◽  
pp. 700-706 ◽  
Author(s):  
Joachim Sieper ◽  
Désirée van der Heijde ◽  
Maxime Dougados ◽  
L Steve Brown ◽  
Frederic Lavie ◽  
...  

ObjectivesTo describe the efficacy and safety through 5 years of adalimumab treatment in patients with ankylosing spondylitis (AS), and to identify predictors of remission.MethodsPatients with active AS were followed up to 5 years during a 24-week randomised, controlled period, followed by an open-label extension. Disease activity and clinical improvement were evaluated by Assessment in Spondyloarthritis International Society (ASAS) responses, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS). Kaplan–Meier was used to identify patients with sustained ASAS partial remission (PR) or ASDAS inactive disease (ID) for three or more consecutive visits spanning ≥6 months. Logistic regression was used to identify factors associated with remission. Explanatory variables included baseline demographic and disease characteristics and week 12 responses.ResultsOf the 311 patients who received at least one dose of adalimumab, 202 (65%) completed the 5-year study. Among 125 patients who received 5 years of adalimumab, 70%, 77%, 51% and 61% achieved ASAS40, BASDAI 50, ASAS PR and ASDAS ID, respectively. Of 311 adalimumab-treated patients, 45% and 55% achieved sustained ASAS PR and ASDAS ID at any time during study participation. The strongest predictor of remission at years 1 and 5 and of sustained remission was achieving remission at 12 weeks of treatment; baseline characteristics showed weaker associations. Adverse events were comparable with previous reports on adalimumab safety.ConclusionsIn patients with active AS, the efficacy and safety of adalimumab were maintained through 5 years with about half of the patients experiencing sustained remission at any time during the study. Early achievement of remission was the best predictor of long-term and sustained remission.


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.


2011 ◽  
Vol 70 (6) ◽  
pp. 1099-1103 ◽  
Author(s):  
M F Bakker ◽  
J W G Jacobs ◽  
P M J Welsing ◽  
S A Vreugdenhil ◽  
C van Booma-Frankfort ◽  
...  

ObjectiveTo investigate the long-term effects of the tight control (TC) and conventional (CT) methotrexate-based strategies of the Computer Assisted Management in Early Rheumatoid Arthritis trial in early rheumatoid arthritis and evaluate the predictive value of an early response to treatment.MethodsClinical and radiographic 5-year outcome was compared between initial strategies. Patients were classified according to the EULAR response criteria. The prognostic value of early response to treatment in addition to established predictors was analysed by multiple linear regression analyses.Results5 years of data were available for 205 of 299 patients, with no indication for selective drop-out. At 5 years there was no longer any significant difference for clinical and radiographic outcomes between treatment strategies applied during the first 2 years. Good-responders had a mean disease activity score of 2.39 (1.2) and median yearly radiographic progression rate of 0.6 (0.0 to 2.2) at 5 years; significantly lower (both p<0.02) when compared to moderate- and non-responders. Multiple regression analysis showed that early response to treatment is an independent predictor of 5-year outcome, irrespective of treatment strategy.ConclusionsThe difference in disease activity between treatment strategies disappeared over the years. Good-response to treatment independently predicts significantly better 5-year clinical and radiographic outcome. The TC principle probably should be continued in the long-term.


2018 ◽  
Vol 77 (7) ◽  
pp. 996-1002 ◽  
Author(s):  
Jens Klotsche ◽  
Kirsten Minden ◽  
Martina Niewerth ◽  
Gerd Horneff

ObjectivesTo determine the reasons of methotrexate (MTX) discontinuation, frequency of adverse events (AE) and whether the time in inactive disease before MTX withdrawal disease is associated with the risk of disease flare.MethodsPatients with juvenile idiopathic arthritis (JIA) beginning treatment with MTX were prospectively observed in the national JIA biologic register Biologika in der Kinderrheumatologie/Biologics in Paediatric Rheumatology and its follow-up register Juvenile arthritis Methotrexate/Biologics long-term Observation. Inactive disease was defined by a clinical Juvenile Arthritis Disease Activity Score ≤1, flare after MTX discontinuation by reoccurrence of at least moderate disease activity or restart of treatment with a disease-modifying antirheumatic drug .ResultsMTX treatment was initiated in 1514 patients after a mean disease duration of 2.1 years (SD=2.8). 40% of the patients experienced oligoarticular onset of JIA. MTX was discontinued in 982 (64.9%) patients. Ineffectiveness (36.9%) and achieving inactive disease (32.1%) were the most common reasons. Among the latter (n=316), 184 (58.2%) patients experienced a flare on follow-up. The likelihood of a flare was a function of time in inactive disease prior to MTX discontinuation (HR 0.95; 95% CI 0.92 to 0.97). Patients with inactive disease for longer than 12 months had a significantly lower flare rate (58 of 119, 48.7%; HR 0.48; 95% CI 0.34 to 0.69). The most frequently reported AE was MTX intolerance, including nausea, aversion and vomiting, accounting for 441 events (13.0 events/100 exposure years) in 307 (20.3%) patients.ConclusionsPatients who spent at least 12 months in inactive disease before MTX discontinuation had a significantly lower flare rate.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1162.2-1162
Author(s):  
E. Pogozheva ◽  
A. Karateev ◽  
V. Amirdzhanova ◽  
E. Filatova

Objectives:to evaluate the efficacy of long-term pain therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with rheumatoid arthritis (RA) with an initially moderate disease activity (DAS 28 <5,1).Methods:the study included 404 RA patients, disease duration was more than 1 year, mean DAS 28 3.7±1.6, mean age 58.6±10.0 years, 69% women, 76,7% RF “+”, 81,5% ACPA “+”. 91,2% of the patients received conventional DMARDs (methotrexate), 8,8% - biological agents. All patients received NSAIDs (aceclofenac) to control their symptoms. Тhe follow-up period was 6 months. We evaluated the dynamics of the DAS 28 index, the level of pain and patient global health on a 100- mm visual analog scale (VAS).Results:the level of pain (VAS) decreased from 63,1 ± 15,4 to 46,3± 8,3 (p=0,001) by 3 months of follow-up and up to 39,5± 11,2 (p= 0,001) by 6 months of follow-up. The patient global health (VAS) also improved from 58,2 ± 13,4 at baseline to 40,3 ± 11,2 (p=0,001) at 3 months and to 35,5 ± 9,7 (p=0,001) at 6 months of follow up. The mean DAS 28 remained within the moderate disease activity and decreased from 3,7±1,5 to 3,4 ±1,1 (p=0,01) after 3 months, and to 3,1± 0,9 (p=0,01) after 6 months.Conclusion:long-term NSAID therapy allows to control the disease activity in patients with moderate RA. This should be taken into account when planning therapy, including deciding whether to “switch” DMARDs and prescribing biological agents.Disclosure of Interests:None declared


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


2018 ◽  
Vol 56 (3) ◽  
pp. 316-320
Author(s):  
N. V. Demidova ◽  
E. A. Galushko ◽  
S. I. Glukhova ◽  
N. M. Savushkina ◽  
A. M. Satybaldyev ◽  
...  

Objective: to assess whether adalimumab (AD) can be gradually discontinued during continuous methotrexate (MTX) use in patients with early rheumatoid arthritis (ERA).Subjects and methods. Within the REMARCA (the Russian study of methotrexate and biological agents in early active arthritis) study, the investigators examined 20 patients (17 women and 3 men; median age, 51 [41.5; 56] years) with ERA (disease duration, 10 [5.5; 20] months; DAS28, 5.17 [4.37; 6.51]; 85% of the patients were seropositive for rheumatoid factor and 85% for anti-cyclic citrullinated peptide antibodies.Results and discussion. All the patients received subcutaneous MTX 25 mg/week. Twelve weeks after beginning therapy with MTX, due to its inefficiency, ADA was added according to the standard scheme. At week 24, the median DAS28 was 3.0 [1.65; 3.73]; 85% of the patients achieved remission or low disease activity. After 3 months of ADA therapy, high or moderate disease activity remained in 3 (15%) patients; median DAS28 was 4.4 [4.3; 6.1]; the drug was discontinued in them due to ineffective therapy. After 12-month follow-up, low DAS28 scores were observed in 5 (29.4%), DAS28 remission was in 12 (70.6%) of the 17 patients who continued ADA treatment; after 24 months, all the 17 patients were noted to have remission. After achieving sustained remission (≥ 6-month duration during ADA therapy), there was a carefully controlled reduction (titration) in the dose of ADA with its complete discontinuation, by maintaining remission at 36-month follow-up; the median DAS28 was 1.6 [1.4; 2.2]. During ADA treatment, one female patient developed pustular psoriasis and therefore the drug was discontinued at 24-month follow-up during the period of sustained remission. Other serious adverse events and tuberculosis cases were not recorded.Conclusion. Thus, the results of the study are indicative of the high clinical efficiency of the therapy. After ADA discontinuation, sustained remission can be maintained in patients with ERA and if they took biological agents early. 


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