Flare Rate in Patients with Rheumatoid Arthritis in Low Disease Activity or Remission When Tapering or Stopping Synthetic or Biologic DMARD: A Systematic Review

2015 ◽  
Vol 42 (11) ◽  
pp. 2012-2022 ◽  
Author(s):  
T. Martijn Kuijper ◽  
Femke B.G. Lamers-Karnebeek ◽  
Johannes W.G. Jacobs ◽  
Johanna M.W. Hazes ◽  
Jolanda J. Luime

Objective.To evaluate the risk of having a disease flare in patients with rheumatoid arthritis (RA) with low disease activity (LDA) or in remission when deescalating (tapering or stopping) disease-modifying antirheumatic drug (DMARD) therapy.Methods.A search in medical databases including publications from January 1950 to February 2015 was performed. Included were trials and observational studies in adults with RA who were in LDA or remission, evaluating ≥ 20 patients tapering or stopping DMARD. Flare rates had to have been reported. A metaanalysis was performed on studies deescalating tumor necrosis factor (TNF) blockers.Results.Four studies evaluated synthetic DMARD. Flare rates ranged from 8% at 24 weeks to 63% at 4 months after deescalation. Fifteen studies reported on TNF blockers. Estimated flare rates by metaanalysis on studies tapering or stopping TNF blockers were 0.26 (95% CI 0.17–0.39) and 0.49 (95% CI 0.27–0.73) for good-quality and moderate-quality studies, respectively. Flare rates in 3 studies stopping tocilizumab were 41% after 6 months, 55% at 1 year, and 87% at 1 year. Flare rates in 3 studies deescalating abatacept were 34% at 1 year, 41% at 1 year, and 72% at 6 months. Five studies evaluating radiographic progression in patients deescalating treatment all found limited to no progression.Conclusion.Results suggest that more than one-third of patients with RA with LDA or in remission may taper or stop DMARD treatment without experiencing a disease flare within the first year. Dose reduction of TNF blockers results in lower flare rates than stopping and may be noninferior to continuing full dose. Radiological progression after treatment deescalation remains low, but may increase slightly.

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.


2021 ◽  
pp. jrheum.201467
Author(s):  
Katerina Chatzidionysiou ◽  
Merete Lund Hetland ◽  
Thomas Frisell ◽  
Daniela Di Giuseppe ◽  
Karin Hellgren ◽  
...  

Objective In Rheumatoid Arthritis (RA), evidence regarding the effectiveness of a second biologic Disease Modifying Anti-Rheumatic Drugs (bDMARDs) in patients whose first ever bDMARD was a non-tumor-necrosis-factor-inhibitor (TNFi) bDMARD is limited. The objective of this study was therefore to assess the outcome of the second bDMARD (non-TNFi [rituximab, abatacept or tocilizumab, separately] and TNFi) after failure of a non-TNFi bDMARD as first bDMARD. Methods We identified RA patients from the five Nordic biologics registers started treatment with a non-TNFi as first ever bDMARD but switched to a second bDMARD. For the second bDMARD, we assessed survival-on-drug (at 6 and 12 months), and primary response (at 6 months). Results We included 620 patients starting a second bDMARD (ABA 86, RTX 40, TCZ 67 and TNFi 427) following failure of a first non-TNFI bDMARD. At 6 and 12 months after start of their second bDMARD, around 70% and 50%, respectively, remained on treatment, and at 6 months less than one third of patients were still on their second bDMARD and had reached low disease activity or remission according to DAS28. For those patients whose second bMDARD was a TNFI, the corresponding proportion was slightly higher (40%). Conclusion The survival-on-drug and primary response of a second bDMARD in RA patients switching due to failure of a non-TNFi bDMARD as first bDMARD is modest. Some patients may benefit from TNFi when used after failure of a non-TNFi as first bDMARD.


Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Melanie J Martin ◽  
Nora Ng ◽  
Laura Blackler ◽  
Toby Garrood

Abstract Background Patients with rheumatoid arthritis are generally seen at arbitrary intervals in secondary care. Patients with active disease may not always be seen at the most appropriate time and those with low disease activity may be seen more frequently than necessary. The NHS Long Term Plan expects outpatient appointments to be reduced by up to a third, with digital transformation a key enabler. The remote capture of patient-reported outcome measures (PROMs) has the potential to facilitate more flexible and responsive outpatient services. Methods This project aimed to design a digital remote monitoring platform to test the hypothesis that PROMs can be used to proactively monitor and trigger consultations when patients need them most. The Rheumatoid Arthritis Impact of Disease (RAID) questionnaire, a validated multidimensional PROM, was used. Waiting room testing with patients informed the design of an acceptable mobile device format of the RAID. Recruitment criteria and acceptable cut-offs for defining flare were agreed by the rheumatology multidisciplinary team. Patients in low disease activity or remission (DAS <3.2) were invited to the service via SMS. All patients were informed regarding the governance of handling patient data and an opt-out option was offered. Patients were sent an automated monthly SMS with a PROM link and weekly reminder SMS if required. They also had the option to send in SMS messages at other times or add free text comments. Patients submitting a RAID score of ≥ 4 received a SMS with a link to the rheumatology advice service advising a remote consultation. The SMS-based service went live in January 2019 and all incoming communication was monitored on a daily basis. Results 104 RA patients are currently using the remote monitoring service with 10.3% (13/117) opting-out. 847 monthly PROMs have been sent via SMS. The PROM completion rate has been 68.9% (range 59.0-85.1%). 120 RAID (21.8%) scored 2-≤4 indicating low disease activity and 136 RAID (24.7%) ≤ 2 indicating disease remission. 480 SMS have been sent manually to patients who have engaged in two-way communication or returned a RAID score ≥4. 44 telephone advice appointments were triggered through the remote monitoring service by patients in disease flare. 80% (35/44) of remote consultation were considered to have to have averted a face to face consultation with the remaining 20% providing advice alone. Interviews have been conducted with PROM ‘non-completers’ to learn and inform further service design. Conclusion This project has demonstrated how a user-centred design approach to utilising technology can support access to rheumatology care when patients need it most, such as disease flare. The identification of patients self-reporting low disease activity using multidimensional PROMs may enable more efficient utilisation of clinical capacity through patient-initiated appointment deferment and lead to improved patient-centred care. Disclosures M.J. Martin: Honoraria; Novartis, Abbvie. Grants/research support; National Ankylosing Spondylitis Society. N. Ng None. L. Blackler None. T. Garrood None.


2014 ◽  
Vol 74 (6) ◽  
pp. 1150-1155 ◽  
Author(s):  
Arthur Kavanaugh ◽  
Susan J Lee ◽  
Jeffrey R Curtis ◽  
Jeffrey D Greenberg ◽  
Joel M Kremer ◽  
...  

BackgroundThere is increasing interest in discontinuing biological therapies for patients with rheumatoid arthritis (RA) achieving good clinical responses, provided patients maintain clinical benefit.MethodsWe assessed patients with RA from the Corrona registry who discontinued treatment with their first tumour necrosis factor inhibitor (TNFi) while in low-disease activity (LDA) or lower levels of disease activity. Patients were followed until they lost clinical benefit, defined as increased disease activity or change in RA medications. Duration of maintenance of clinical benefit was estimated using the Kaplan–Meier method. Cox proportional hazard models were assessed to identify factors related to maintenance of benefit.ResultsWe identified 717 eligible patients with RA from 35 656 in the Corrona registry. At discontinuation, patients had a median RA duration of 8 years, mean clinical disease activity score of 4.3±0.11; 41.8% were using TNFi as monotherapy. 73.4% of patients maintained benefit for >12 months after discontinuing therapy and 42.2% did so through 24 months. Factors predictive of maintaining clinical benefit in multivariate analysis included lower disease activity, less pain and better functional status at the time of TNFi discontinuation. Among 301 patients initiating their first TNFi within the registry, faster responders (ie, those who achieved LDA in 4 months or less) did better than slower responders (HR 1.54 (95% CI 1.17 to 2.04)). RA disease duration did not affect maintenance of clinical benefit.ConclusionsDiscontinuation of a first course of TNFi may be associated with persistent clinical benefit. Half of patients maintained response through 20 months. Several patient characteristics may help predict persistent benefit.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1406.1-1407
Author(s):  
S. H. Nam ◽  
J. S. Lee ◽  
S. J. Choi ◽  
W. J. Seo ◽  
J. S. Oh ◽  
...  

Background:Several recent studies have reported that MTX could be discontinued in patients with low disease activity who are taking biologic DMARDs or tofacitinib. However, there are limited studies on whether MTX could be discontinued in patients with low disease activity who have taken MTX for a long term.Objectives:We investigated the disease flare rate in patients with rheumatoid arthritis (RA) who achieved low disease activity following long-term methotrexate (MTX) treatment and the factors related to flare.Methods:This retrospective longitudinal cohort study included patients with RA and low disease activity who were exposed to MTX for >10 years. Disease flare was defined as an increase in DAS28 of >1.2 within 6 months of discontinuation of MTX. Logistic regression analysis was performed to identify the factors associated with flare.Results:In total, 97 patients with RA were included in the study. The mean baseline DAS28 was 1.96 ± 0.56. The median cumulative MTX dose was 11.7g; the median duration of exposure to MTX was 19 years. Following MTX discontinuation, flare occurred in 43 (44.3%) patients; the mean time to flare was 98 ± 37.7 days. According to univariable logistic regression analysis, C-reactive protein, erythrocyte sedimentation rate (ESR) at discontinuation, the average ESR in the 6 months before discontinuation of MTX, a weekly dose of MTX before discontinuation, and use of other conventional synthetic DMARDs were associated with a higher risk of disease flare. In multivariable analysis, a weekly dose of MTX before discontinuation (OR, 1.014; 95% CI, 1.014–1.342; p = 0.031) was significantly associated with flare risk.Conclusion:Among patients with RA who achieved low disease activity with long-term treatment with MTX, more than half of the patients remained flare free after MTX discontinuation. A higher MTX dose before discontinuation was associated with a high flare risk.Disclosure of Interests:None declared


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