Tumour necrosis factor inhibitor dose adaptation in psoriatic arthritis and axial spondyloarthritis (TAPAS): a retrospective cohort study

Abstract Objectives We investigated the effect of disease activity-guided dose optimization (DAGDO) of TNF inhibitor (TNFi) on disease activity and TNFi dose in PsA and axial spondyloarthritis (axSpA) patients with low disease activity (LDA). Methods A retrospective cohort study was conducted in PsA and axSpA patients doing well on TNFi and eligible for TNFi DAGDO. Three different treatment periods were defined: (i) full dose continuation period, (ii) TNFi DAGDO period, and (iii) period with stable TNFi dose after DAGDO. A mixed-model analysis was used to estimate mean Disease Activity Score 28-joint count CRP (DAS28-CRP) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) during these periods, and a mean percentage of the daily defined dose (%DDD) was calculated as secondary outcome. Results Three hundred and twenty-four patients (153 PsA and 171 axSpA) were included, with a mean of 6.5 DAS28-CRP and 6.4 BASDAI measurements and a median follow-up duration of 46 and 44 months, respectively. A corrected difference of 0.06 (95% CI: −0.09, 0.21) in mean DAS28-CRP was found for the TNFi DAGDO period and 0.03 (95% CI: −0.14, 0.20) for the period with stable TNFi dose, compared with full dose continuation period. Differences for BASDAI were 0.03 (95% CI: −0.21, 0.27) and 0.05 (95% CI: −0.24, 0.34), respectively. The mean %DDD for the three treatment periods was for PsA 108%, 62% and 78%, and for axSpA 108%, 62% and 72%, respectively. Conclusion DAGDO of TNFi reduces drug exposure and has no negative effects on disease activity in PsA and axSpA patients compared with full dose continuation.

[1]  M. Picot,et al.  OP0138 FEASIBILITY OF PROGRESSIVE ANTI-TNF TAPERING IN AXIAL SPONDYLOARTHRITIS PATIENTS IN LOW DISEASE ACTIVITY: RESULTS FROM THE MULTICENTER NON-INFERIORITY PROSPECTIVE RANDOMIZED CONTROLLED TRIAL SPACING , 2021 .

[2]  M. Dougados,et al.  Efficacy of a tight-control and treat-to-target strategy in axial spondyloarthritis: results of the open-label, pragmatic, cluster-randomised TICOSPA trial , 2021, Annals of the Rheumatic Diseases.

[3]  L. Coates,et al.  Withdrawing Ixekizumab in Patients With Psoriatic Arthritis Who Achieved Minimal Disease Activity: Results From a Randomized, Double‐Blind Withdrawal Study , 2021, Arthritis & rheumatology.

[4]  P. Machado.  Faculty Opinions recommendation of 2019 update of the american college of rheumatology/spondylitis association of america/spondyloarthritis research and treatment network recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis. , 2020, Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature.

[5]  J. Primdahl,et al.  EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2019 update , 2020, Annals of the Rheumatic Diseases.

[6]  M. Dougados,et al.  Maintenance of clinical remission in early axial spondyloarthritis following certolizumab pegol dose reduction , 2020, Annals of the Rheumatic Diseases.

[7]  T. Barnetche,et al.  Impact of tapering targeted therapies (bDMARDs or JAKis) on the risk of serious infections and adverse events of special interest in patients with rheumatoid arthritis or spondyloarthritis: a systematic analysis of the literature and meta-analysis , 2020, Arthritis Research & Therapy.

[8]  Tsutomu Takeuchi,et al.  EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update , 2020, Annals of the Rheumatic Diseases.

[9]  D. M. van der Heijde,et al.  Dose reduction and withdrawal strategy for TNF-inhibitors in psoriatic arthritis and axial spondyloarthritis: design of a pragmatic open-label, randomised, non-inferiority trial , 2020, Trials.

[10]  M. Ward,et al.  2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis , 2019, Arthritis care & research.

[11]  E. de Miguel,et al.  Non-inferiority of dose reduction versus standard dosing of TNF-inhibitors in axial spondyloarthritis , 2019, Arthritis Research & Therapy.

[12]  P. Creamer,et al.  Dose reduction of biologic therapy in inflammatory arthritis: A qualitative study of patients' perceptions and needs , 2018, Musculoskeletal care.

[13]  L. Coates,et al.  Tapering and Discontinuation of Biologics in Patients with Psoriatic Arthritis with Low Disease Activity , 2018, Drugs.

[14]  R. Landewé,et al.  Efficacy and safety of continuing versus withdrawing adalimumab therapy in maintaining remission in patients with non-radiographic axial spondyloarthritis (ABILITY-3): a multicentre, randomised, double-blind study , 2018, The Lancet.

[15]  Ting Zhang,et al.  Analysis of relapse rates and risk factors of tapering or stopping pharmacologic therapies in axial spondyloarthritis patients with sustained remission , 2018, Clinical Rheumatology.

[16]  F. Hoogen,et al.  Subjective Complaints as the Main Reason for Biosimilar Discontinuation After Open‐Label Transition From Reference Infliximab to Biosimilar Infliximab , 2018, Arthritis & rheumatology.

[17]  E. Frati,et al.  Low Doses of Etanercept Can Be Effective to Maintain Remission in Psoriatic Arthritis Patients , 2017, Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases.

[18]  M. Hulscher,et al.  bDMARD Dose Reduction in Rheumatoid Arthritis: A Narrative Review with Systematic Literature Search , 2017, Rheumatology and Therapy.

[19]  M. Dougados,et al.  2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis , 2017, Annals of the rheumatic diseases.

[20]  P. Mease,et al.  Persistence of low disease activity after tumour necrosis factor inhibitor (TNFi) discontinuation in patients with psoriatic arthritis , 2017, RMD Open.

[21]  Marien González-Lorenzo,et al.  Risk of infections using anti-TNF agents in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis: a systematic review and meta-analysis , 2016, Expert opinion on drug safety.

[22]  F. V. D. van den Hoogen,et al.  Little Evidence for Usefulness of Biomarkers for Predicting Successful Dose Reduction or Discontinuation of a Biologic Agent in Rheumatoid Arthritis: A Systematic Review , 2016, Arthritis & rheumatology.

[23]  E. Martı́n-Mola,et al.  Anti-TNF discontinuation and tapering strategies in patients with axial spondyloarthritis: a systematic literature review. , 2016, Rheumatology.

[24]  E. Akl,et al.  American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015 Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis , 2016, Arthritis & rheumatology.

[25]  M Cutolo,et al.  European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update , 2015, Annals of the rheumatic diseases.

[26]  P. Tugwell,et al.  Risk of serious infection in biological treatment of patients with rheumatoid arthritis: a systematic review and meta-analysis , 2015, The Lancet.

[27]  H. Doll,et al.  Is Etanercept 25 mg Once Weekly as Effective as 50 mg at Maintaining Response in Patients with Ankylosing Spondylitis? A Randomized Control Trial , 2015, The Journal of Rheumatology.

[28]  M. Dougados,et al.  Preliminary definitions of ‘flare’ in axial spondyloarthritis, based on pain, BASDAI and ASDAS-CRP: an ASAS initiative , 2015, Annals of the rheumatic diseases.

[29]  J. Bijlsma,et al.  Disease activity guided dose reduction and withdrawal of adalimumab or etanercept compared with usual care in rheumatoid arthritis: open label, randomised controlled, non-inferiority trial , 2015, BMJ : British Medical Journal.

[30]  D. M. van der Heijde,et al.  How much does Disease Activity Score in 28 joints ESR and CRP calculations underestimate disease activity compared with the Simplified Disease Activity Index? , 2014, Annals of the rheumatic diseases.

[31]  L. Coates,et al.  Effect of tight control of inflammation in early psoriatic arthritis (TICOPA): a UK multicentre, open-label, randomised controlled trial , 2014, The Lancet.

[32]  G. Schett,et al.  High incidence of disease recurrence after discontinuation of disease-modifying antirheumatic drug treatment in patients with psoriatic arthritis in remission , 2013, Annals of the rheumatic diseases.

[33]  S. Chimenti,et al.  Remission of Psoriatic Arthritis after Etanercept Discontinuation: Analysis of Patients' Clinical Characteristics Leading to Disease Relapse , 2013, International journal of immunopathology and pharmacology.

[34]  O. Madsen.  Agreement Between the DAS28-CRP Assessed with 3 and 4 Variables in Patients with Rheumatoid Arthritis Treated with Biological Agents in the Daily Clinic , 2013, The Journal of Rheumatology.

[35]  F. Cantini,et al.  Duration of remission after halving of the etanercept dose in patients with ankylosing spondylitis: a randomized, prospective, long-term, follow-up study , 2013, Biologics : targets & therapy.

[36]  P. V. van Riel,et al.  Construct and criterion validity of several proposed DAS28-based rheumatoid arthritis flare criteria: an OMERACT cohort validation study , 2012, Annals of the rheumatic diseases.

[37]  Michael J. Green,et al.  Sensitivity and specificity of the classification of psoriatic arthritis criteria in early psoriatic arthritis. , 2012, Arthritis and rheumatism.

[38]  H. Zeidler,et al.  Treatment of active ankylosing spondylitis with infliximab: a randomised controlled multicentre trial , 2002, The Lancet.

[39]  M. Hulscher,et al.  Down-titration and discontinuation strategies of tumour necrosis factor-blocking agents for rheumatoid arthritis in patients with low disease activity. , 2019, The Cochrane database of systematic reviews.