Randomized Controlled Trial

. 2021 Nov;80(11):1436-1444.

doi: 10.1136/annrheumdis-2020-219585. Epub 2021 May 6.

Efficacy of a tight-control and treat-to-target strategy in axial spondyloarthritis: results of the open-label, pragmatic, cluster-randomised TICOSPA trial

Anna Molto^{1

2}, Clementina López-Medina^{2

3}, Filip E Van den Bosch⁴, Annelies Boonen^{5

6}, Casper Webers^{5

6}, Emanuelle Dernis⁷, Floris A van Gaalen⁸, Martin Soubrier⁹, Pascal Claudepierre^{10

11}, Athan Baillet^{12

13}, Mirian Starmans-Kool¹⁴, Anneke Spoorenberg¹⁵, Peggy Jacques^{4

16}, Philippe Carron^{16

17}, Rik Joos¹⁸, Jan Lenaerts¹⁹, Laure Gossec^{20

21}, Sophie Pouplin²², Adeline Ruyssen-Witrand^{23

24}, Laetitia Sparsa²⁵, Astrid van Tubergen²⁶, Désirée van der Heijde²⁷, Maxime Dougados^{28

2}

Affiliations

¹ Rheumatology Department, Hospital Cochin, Paris, France anna.molto@aphp.fr.
² ECAMO team, INSERM U1153, Paris, France.
³ Rheumatology Department, Reina Sofia University Hospital, Cordoba, Andalucía, Spain.
⁴ Rheumatology Department, University Hospital Ghent, Gent, Oost-Vlaanderen, Belgium.
⁵ Department of Internal Medicine, Division of Rheumatology, Maastricht University, Maastricht, The Netherlands.
⁶ Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, The Netherlands.
⁷ Rheumatology Department, Le Mans Hospital, Le Mans, France.
⁸ Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
⁹ Rheumatology, CHU, Clermont-Ferrand, France.
¹⁰ Rheumatology, Henri Mondor Hospital Rheumatology Service, Creteil, France.
¹¹ EpiDermE, Université Paris Est Créteil, Créteil, France.
¹² Rheumatology, Hopital Sud, Echirolles, France.
¹³ GREPI EA7408, Universite Grenoble Alpes, Saint-Martin-d'Heres, France.
¹⁴ Rheumatology, Zuyderland Medical Centre Heerlen, Heerlen, The Netherlands.
¹⁵ Rheumatology & Clinical Immunology, University Medical Centre Groningen, Groningen, The Netherlands.
¹⁶ Rheumatology, VIB-UGent Center for Inflammation Research, Zwijnaarde, Belgium.
¹⁷ Rheumatology, University Hospital Ghent, Gent, Belgium.
¹⁸ Rheumatology, ZNA UKJA, Antwerpen, Belgium.
¹⁹ Rheumatology, Reumainstituut Hasselt, Hasselt, Belgium.
²⁰ Rheumatology Department, University Hospital Pitié Salpêtrière, Paris, France.
²¹ Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France.
²² Rheumatology, Bois-Guillaume CHU, Rouen, France.
²³ Rheumatology, University Hospital Centre Toulouse, Toulouse, France.
²⁴ Paul Sabatier University, Toulouse, France.
²⁵ Rheumatology department, Hospital Centre Mulhouse, Mulhouse, France.
²⁶ Department of Medicine, Division of Rheumatology, Maastricht University Medical Center, Maastricht, The Netherlands.
²⁷ Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
²⁸ Rheumatology Department, Hospital Cochin, Paris, France.

PMID: 33958325
PMCID: PMC8522451
DOI: 10.1136/annrheumdis-2020-219585

Randomized Controlled Trial

Efficacy of a tight-control and treat-to-target strategy in axial spondyloarthritis: results of the open-label, pragmatic, cluster-randomised TICOSPA trial

Anna Molto et al. Ann Rheum Dis. 2021 Nov.

. 2021 Nov;80(11):1436-1444.

doi: 10.1136/annrheumdis-2020-219585. Epub 2021 May 6.

Authors

Affiliations

¹ Rheumatology Department, Hospital Cochin, Paris, France anna.molto@aphp.fr.
² ECAMO team, INSERM U1153, Paris, France.
³ Rheumatology Department, Reina Sofia University Hospital, Cordoba, Andalucía, Spain.
⁴ Rheumatology Department, University Hospital Ghent, Gent, Oost-Vlaanderen, Belgium.
⁵ Department of Internal Medicine, Division of Rheumatology, Maastricht University, Maastricht, The Netherlands.
⁶ Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, The Netherlands.
⁷ Rheumatology Department, Le Mans Hospital, Le Mans, France.
⁸ Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
⁹ Rheumatology, CHU, Clermont-Ferrand, France.
¹⁰ Rheumatology, Henri Mondor Hospital Rheumatology Service, Creteil, France.
¹¹ EpiDermE, Université Paris Est Créteil, Créteil, France.
¹² Rheumatology, Hopital Sud, Echirolles, France.
¹³ GREPI EA7408, Universite Grenoble Alpes, Saint-Martin-d'Heres, France.
¹⁴ Rheumatology, Zuyderland Medical Centre Heerlen, Heerlen, The Netherlands.
¹⁵ Rheumatology & Clinical Immunology, University Medical Centre Groningen, Groningen, The Netherlands.
¹⁶ Rheumatology, VIB-UGent Center for Inflammation Research, Zwijnaarde, Belgium.
¹⁷ Rheumatology, University Hospital Ghent, Gent, Belgium.
¹⁸ Rheumatology, ZNA UKJA, Antwerpen, Belgium.
¹⁹ Rheumatology, Reumainstituut Hasselt, Hasselt, Belgium.
²⁰ Rheumatology Department, University Hospital Pitié Salpêtrière, Paris, France.
²¹ Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France.
²² Rheumatology, Bois-Guillaume CHU, Rouen, France.
²³ Rheumatology, University Hospital Centre Toulouse, Toulouse, France.
²⁴ Paul Sabatier University, Toulouse, France.
²⁵ Rheumatology department, Hospital Centre Mulhouse, Mulhouse, France.
²⁶ Department of Medicine, Division of Rheumatology, Maastricht University Medical Center, Maastricht, The Netherlands.
²⁷ Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
²⁸ Rheumatology Department, Hospital Cochin, Paris, France.

PMID: 33958325
PMCID: PMC8522451
DOI: 10.1136/annrheumdis-2020-219585

Abstract

Objectives: To compare the benefits of a tight-control/treat-to-target strategy (TC/T2T) in axial spondyloarthritis (axSpA) with those of usual care (UC).

Methods: Pragmatic, prospective, cluster-randomised, controlled, open, 1-year trial (NCT03043846). 18 centres were randomised (1:1). Patients met Axial Spondylo Arthritis International Society (ASAS) criteria for axSpA, had an Ankylosing Spondylitis Disease Activity Score (ASDAS) ≥2.1, received non-optimal treatment by non-steroidal anti-inflammatory drugs and were biologic-naive.

Interventions: (1) TC/T2T: visits every 4 weeks and prespecified strategy based on treatment intensification until achieving target (ie, ASDAS <2.1); (2) UC: visits every 12 weeks and treatment at the rheumatologist's discretion.

Main outcome: Percentage of patients with a ≥30% improvement on the ASAS-Health Index (ASAS-HI). Other efficacy outcomes and adverse events were recorded. A health economic evaluation was performed.

Statistical analysis: Two-level mixed models were used to estimate efficacy outcomes. Cost-effectiveness was assessed by the incremental cost per quality-adjusted life-year (QALY) gained for TC/T2T versus UC.

Results: 160 patients were included (80/group). Mean (SD) age was 37.9 (11.0) years and disease duration was 3.7 (6.2) years; 51.2% were men. ASDAS at inclusion was 3.0 (0.7), and ASAS-HI was 8.6 (3.7). ASAS-HI improved by ≥30% in 47.3% of the TC/T2T arm and in 36.1% of those receiving UC (non-significant). All secondary efficacy outcomes were more frequent in the TC/T2T arm, although not all statistically significant. Safety was similar in both arms. From a societal perspective, TC/T2T resulted in an additional 0.04 QALY, and saved €472 compared with UC.

Conclusion: TC/T2T was not significantly superior to UC for the primary outcome, while many secondary efficacy outcomes favoured it, had a similar safety profile and was favourable from a societal health economic perspective.

Trial registration number: NCT03043846.

Keywords: ankylosing; healthcare; outcome and process assessment; spondylitis; therapeutics.

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Conflict of interest statement

Competing interests: Dr van Tubergen reports grants and personal fees from Novartis, grants from Pfizer, grants from UCB, grants from Biogen, grants from AbbVie, outside the submitted work. Dr van der Heijde reports personal fees from AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli-Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma, outside the submitted work; and Director of Imaging Rheumatology bv. Dr van Gaalen reports grants from Stichting vrienden van Sole Mio, grants from Stichting ASAS, grants and personal fees from Novartis, grants from UCB, personal fees from MSD, personal fees from AbbVie, personal fees from Bristol Myers Squibb, outside the submitted work. AB received a research grant to her department from AbbVie, consultation fees from Eli Lilly and Galapagos and a speakers fee from UCB, all paid to her department. Dr Van den Bosch reports personal fees from AbbVie, personal fees from Celgene, personal fees from Eli Lilly, personal fees from Galapagos, personal fees from Janssen, personal fees from Novartis, personal fees from Pfizer, personal fees from UCB, outside the submitted work. Dr Claudepierre reports personal fees from Roche Chugai, Novartis, Pfizer, MSD, grants from Roche Chugai, Novartis, Pfizer, UCB, MSD, AbbVie, Lilly, Celgene, Janssen, BMS, outside the submitted work. Dr Molto reports grants from UCB during the conduct of the study; personal fees from AbbVie, grants and personal fees from UCB, personal fees from BMS, grants and personal fees from Pfizer, grants and personal fees from MSD, personal fees from Novartis, personal fees from Gilead, personal fees from Lilly, outside the submitted work. Dr Gossec reports grants from Amgen, Lilly, Janssen, Pfizer, Sandoz, Sanofi, Galapagos, personal fees from AbbVie, Amgen, BMS, Biogen, Celgene, Gilead, Janssen, Lilly, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis, UCB, outside the submitted work. Dr Dougados reports grants from UCB, during the conduct of the study; grants and personal fees from AbbVie, grants and personal fees from Pfizer, grants and personal fees from Lilly, grants and personal fees from Novartis, grants and personal fees from Roche, grants and personal fees from BMS, grants and personal fees from Merck, outside the submitted work. Dr Dernis, Dr Ruyssen-Witrand, Dr Lenaerts, Dr Lopez-Medina, Dr Sparsa, Dr Starmans-Kool, Dr C Webers, Dr Pouplin, Dr Soubrier and Dr Joos have nothing to declare.

Figures

**Figure 1**
Flow chart of the study. ASDAS, Ankylosing Spondylitis Disease Activity Score; SpA, spondyloarthritis; TC/T2T, tight control and treat-to-target; UC, usual care.

**Figure 2**
ASAS-HI improvement ≥30%, ASDAS LDA status and ASAS40 response estimated at 48 weeks. *Statistical significance. ASAS-HI, Axial Spondyloarthritis International Society-Health Index; ASDAS, Ankylosing Spondylitis Disease Activity Score; LDA, low disease activity; T2T/TC, treat-to-target and tight control; UC, usual care.

See this image and copyright information in PMC

Comment in

What is the optimal target for a T2T approach in axial spondyloarthritis?
Sieper J, Poddubnyy D. Sieper J, et al. Ann Rheum Dis. 2021 Nov;80(11):1367-1369. doi: 10.1136/annrheumdis-2021-220603. Epub 2021 Jun 18. Ann Rheum Dis. 2021. PMID: 34144966 Free PMC article. No abstract available.
Correspondence on 'Efficacy of a tight-control and treat-to-target strategy in axial spondyloarthritis: results of the open-label, pragmatic, cluster-randomised TICOSPA trial'.
Cai G, Peng X. Cai G, et al. Ann Rheum Dis. 2023 Jul;82(7):e166. doi: 10.1136/annrheumdis-2021-220904. Epub 2021 Jun 29. Ann Rheum Dis. 2023. PMID: 34187774 Clinical Trial. No abstract available.
Response to: 'Correspondence on 'Efficacy of a tight-control and treat-to-target strategy in axial spondyloarthritis: results of the open-label, pragmatic, cluster-randomised TICOSPA trial'' by Cai and Peng.
Molto A, van der Heijde D, Van den Bosch FE, Dougados M. Molto A, et al. Ann Rheum Dis. 2023 Jul;82(7):e167. doi: 10.1136/annrheumdis-2021-220913. Epub 2021 Jun 29. Ann Rheum Dis. 2023. PMID: 34187778 Clinical Trial. No abstract available.
Correspondence on "Efficacy of a tight-control and treat-to-target strategy in axial spondyloarthritis: results of the open-label, pragmatic, cluster-randomised TICOSPA trial" by Molto et al.
Kiltz U, Braun J. Kiltz U, et al. Ann Rheum Dis. 2023 Dec;82(12):e229. doi: 10.1136/annrheumdis-2021-221423. Epub 2021 Nov 1. Ann Rheum Dis. 2023. PMID: 34725049 Clinical Trial. No abstract available.

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Bautista-Molano W, Fernández-Ávila DG, Brance ML, Ávila Pedretti MG, Burgos-Vargas R, Corbacho I, Cosentino VL, Díaz Coto JF, Giraldo Ho E, Gomes Resende G, Gutiérrez LA, Gutiérrez M, Ibáñez Vodnizza SE, Jáuregui E, Ocampo V, Palleiro Rivero DR, Palominos PE, Pacheco Tena C, Quiceno GA, Saldarriaga-Rivera LM, Sommerfleck FA, Goecke Sariego A, Vera Barrezueta C, Vega Espinoza LE, Vega Hinojosa O, Citera G, Lozada C, Sampaio-Barros PD, Schneeberger E, Soriano ER. Bautista-Molano W, et al. Nat Rev Rheumatol. 2023 Nov;19(11):724-737. doi: 10.1038/s41584-023-01034-z. Epub 2023 Oct 6. Nat Rev Rheumatol. 2023. PMID: 37803079

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Efficacy of a tight-control and treat-to-target strategy in axial spondyloarthritis: results of the open-label, pragmatic, cluster-randomised TICOSPA trial

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Efficacy of a tight-control and treat-to-target strategy in axial spondyloarthritis: results of the open-label, pragmatic, cluster-randomised TICOSPA trial

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