Predicting low disease activity and remission using early treatment response to antitumour necrosis factor therapy in patients with rheumatoid arthritis: exploratory analyses from the TEMPO trial

Background. Rheumatoid arthritis is a systemic autoimmune disease characterized by joint erosions, progressive focal bone loss, and chronic inflammation.Methods. 20 female patients with moderate-to-severe rheumatoid arthritis were treated with anti-TNF-antibody adalimumab in addition to concomitant antirheumatic therapies. Patients were assessed for overall disease activity using the DAS28 score, and neopterin, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) concentrations as well as osteoprotegerin (OPG) and soluble receptor activator of NF-κB ligand (sRANKL) concentrations were determined before therapy and at week 12. Neopterin as well as OPG and sRANKL were determined by commercial ELISAs.Results. Before anti-TNF therapy patients presented with high disease activity and elevated concentrations of circulating inflammatory markers. OPG concentrations correlated with neopterin (rs=0.494,p=0.027), but not with DAS28. OPG concentrations and disease activity scores declined during anti-TNF-treatment (bothp<0.02). Patients who achieved remission (n=7) or showed a good response according to EULAR criteria (n=13) presented with initially higher baseline OPG levels, which subsequently decreased significantly during treatment (p=0.018for remission,p=0.011for good response).Conclusions. Adalimumab therapy was effective in modifying disease activity and reducing proinflammatory and bone remodelling cascades.

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086 A longitudinal analysis of prevalence of sustained remission and low disease activity in rheumatoid arthritis patients treated with anti-tumour necrosis factor: an analysis of the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis

Rheumatology ◽

10.1093/rheumatology/key075.310 ◽

2018 ◽

Vol 57 (suppl_3) ◽

Author(s):

Philip D H Hamann ◽

Gavin Shaddick ◽

Neil McHugh ◽

Kimme Hyrich ◽

John D Pauling

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Tumour Necrosis Factor ◽

Longitudinal Analysis ◽

Tumour Necrosis ◽

British Society ◽

Sustained Remission ◽

Low Disease Activity ◽

Necrosis Factor ◽

Biologics Register

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Effectiveness of a second biologic after failure of a non-tumor necrosis factor inhibitor as first biologic in rheumatoid arthritis

The Journal of Rheumatology ◽

10.3899/jrheum.201467 ◽

2021 ◽

pp. jrheum.201467

Author(s):

Katerina Chatzidionysiou ◽

Merete Lund Hetland ◽

Thomas Frisell ◽

Daniela Di Giuseppe ◽

Karin Hellgren ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Tumor Necrosis Factor ◽

Disease Activity ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Inhibitor ◽

Primary Response ◽

Low Disease Activity ◽

Factor Inhibitor ◽

Disease Modifying ◽

Necrosis Factor

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.

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

The Journal of Rheumatology ◽

10.3899/jrheum.141520 ◽

2015 ◽

Vol 42 (11) ◽

pp. 2012-2022 ◽

Cited By ~ 46

Author(s):

T. Martijn Kuijper ◽

Femke B.G. Lamers-Karnebeek ◽

Johannes W.G. Jacobs ◽

Johanna M.W. Hazes ◽

Jolanda J. Luime

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

First Year ◽

Low Disease Activity ◽

Dmard Therapy ◽

Disease Flare ◽

Medical Databases ◽

Tnf Blockers ◽

Biologic Dmard ◽

Necrosis Factor

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.

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Autoantibody status is not associated with early treatment response to first-line methotrexate in patients with early rheumatoid arthritis

Rheumatology ◽

10.1093/rheumatology/key263 ◽

2018 ◽

Vol 58 (1) ◽

pp. 149-153 ◽

Cited By ~ 7

Author(s):

Jacqueline S Dekkers ◽

Sytske Anne Bergstra ◽

Arvind Chopra ◽

Mohammed Tikly ◽

João Eurico Fonseca ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Treatment Response ◽

Early Rheumatoid Arthritis ◽

Early Treatment ◽

First Line ◽

Early Treatment Response ◽

Autoantibody Status

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How do dose reduction and discontinuation of tumor necrosis factor-blocking (anti-TNF) agents affect people with low disease activity rheumatoid arthritis?

Cochrane Clinical Answers ◽

10.1002/cca.2637 ◽

2019 ◽

Author(s):

David S. Edwards

Keyword(s):

Rheumatoid Arthritis ◽

Tumor Necrosis Factor ◽

Disease Activity ◽

Dose Reduction ◽

Tumor Necrosis ◽

Low Disease Activity ◽

Necrosis Factor

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Discontinuation of tumour necrosis factor inhibitors in patients with rheumatoid arthritis in low-disease activity: persistent benefits. Data from the Corrona registry

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2014-206435 ◽

2014 ◽

Vol 74 (6) ◽

pp. 1150-1155 ◽

Cited By ~ 29

Author(s):

Arthur Kavanaugh ◽

Susan J Lee ◽

Jeffrey R Curtis ◽

Jeffrey D Greenberg ◽

Joel M Kremer ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Tumour Necrosis Factor ◽

Clinical Benefit ◽

Tumour Necrosis ◽

Patient Characteristics ◽

Low Disease Activity ◽

Kaplan Meier ◽

Factor Inhibitor ◽

Necrosis Factor

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.

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