Reducing or Maintaining the Dose of Subcutaneous Tocilizumab in Patients With Rheumatoid Arthritis in Clinical Remission: A Randomized, Open-Label Trial

Raimon Sanmarti; Douglas J. Veale; Emilio Martin-Mola; Alejandro Escudero-Contreras; Carlos González; Liliana Ercole; Rocío Alonso; João E. Fonseca; Cristina Alcañiz; José María Álvaro-Gracia; Alejandro Balsa; José Luis de Pablos; Consuelo Díaz Miguel; José Manuel Rodríguez; Jose Alves; Elena Aurrecoechea; Jaime Calvo; Joaquín Belzunegui; Francisco Blanco; Rafael Caliz; Javier Calvo; José Román Ivorra; Helena Canhão; Helena Santos; Eugenio Chamizo; Javier del Pino; Concepción Delgado; César Díaz; Antonio Fernández Nebro; Alexander Fraser; Antonio Gomez; Blanca Hernández; Federico Navarro; Juan Povedano; Antonio Juan Mas; David Kane; Bryan Whelan; Carlos Marras; Juan Moreno; José Pérez Venegas; Manuel Pombo; Elena Riera; Antonio Rosas; John Ryan; José Santos; Maria Santos; Jesús Tornero; Juan Víctor Tovar; Eduardo Ucar; Carlos Vasconcelos

doi:10.1002/art.40905

Reducing or Maintaining the Dose of Subcutaneous Tocilizumab in Patients With Rheumatoid Arthritis in Clinical Remission: A Randomized, Open-Label Trial

Raimon Sanmarti, Douglas J. Veale, Emilio Martin-Mola, Alejandro Escudero-Contreras, Carlos González, Liliana Ercole, Rocío Alonso, João E. Fonseca, Cristina Alcañiz, José María Álvaro-Gracia, Alejandro Balsa, José Luis de Pablos, Consuelo Díaz Miguel, José Manuel Rodríguez, Jose Alves, Elena Aurrecoechea, Jaime Calvo, Joaquín Belzunegui, Francisco Blanco, Rafael CalizJavier Calvo, José Román Ivorra, Helena Canhão, Helena Santos, Eugenio Chamizo, Javier del Pino, Concepción Delgado, César Díaz, Antonio Fernández Nebro, Alexander Fraser, Antonio Gomez, Blanca Hernández, Federico Navarro, Juan Povedano, Antonio Juan Mas, David Kane, Bryan Whelan, Carlos Marras, Juan Moreno, José Pérez Venegas, Manuel Pombo, Elena Riera, Antonio Rosas, John Ryan, José Santos, Maria Santos, Jesús Tornero, Juan Víctor Tovar, Eduardo Ucar, Carlos Vasconcelos

NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)

Research output: Contribution to journal › Article › peer-review

10 Citations (Scopus)

Abstract

Objective: To evaluate the efficacy and safety of increasing the dose interval of subcutaneous tocilizumab (TCZ-SC) in patients with rheumatoid arthritis (RA) who are in clinical remission. Methods: RA patients with active disease and an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or to a biologic agent were entered into a single-arm treatment phase with 162 mg of TCZ-SC administered once weekly (TCZ-SC 162 mg qw) as monotherapy or in combination with a csDMARD for 24 weeks. Patients who achieved clinical remission at weeks 20 and 24 were randomized to continue with the same regimen or to switch to 162 mg TCZ-SC administered every 2 weeks (TCZ-SC 162 mg q2w) for 24 weeks (open-label). Patients with a Disease Activity Score in 28 joints (DAS28) of <2.6 were considered to be in clinical remission. Results: In total, 179 (45%) of 401 patients in the single-arm phase achieved clinical remission and were randomized to continue to receive TCZ-SC 162 mg qw (n = 89) or to switch to TCZ-SC 162 mg q2w (n = 90) for 24 weeks. At week 48, significantly more patients treated with TCZ-SC 162 mg qw remained in clinical remission compared to patients who received TCZ-SC 162 mg q2w (90% versus 73%; P = 0.004). The results of other efficacy measures revealed greater efficacy with TCZ-SC 162 mg qw, but none of the efficacy outcomes in this group were significantly different from those in patients treated with TCZ-SC 162 mg q2w, except for the mean change from baseline in the DAS28 score at week 48 (mean change −4.07 points [SD 1.29] versus −3.65 points [SD 1.35]; P = 0.034). Tolerability and safety parameters were similar between the treatment groups. Conclusion: Increasing the dose interval of TCZ-SC in patients with RA was associated with a lower likelihood of maintaining remission after 24 weeks and was not associated with better tolerability. However, most patients were able to sustain remission with a half-dose of TCZ-SC, and therefore this strategy deserves further investigation.

Original language	English
Pages (from-to)	1616-1625
Number of pages	10
Journal	Arthritis & rheumatology
Volume	71
Issue number	10
DOIs	https://doi.org/10.1002/art.40905
Publication status	Published - 1 Oct 2019

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Sanmarti, R., Veale, D. J., Martin-Mola, E., Escudero-Contreras, A., González, C., Ercole, L., Alonso, R., Fonseca, J. E., Alcañiz, C., Álvaro-Gracia, J. M., Balsa, A., de Pablos, J. L., Miguel, C. D., Rodríguez, J. M., Alves, J., Aurrecoechea, E., Calvo, J., Belzunegui, J., Blanco, F., ... Vasconcelos, C. (2019). Reducing or Maintaining the Dose of Subcutaneous Tocilizumab in Patients With Rheumatoid Arthritis in Clinical Remission: A Randomized, Open-Label Trial. Arthritis & rheumatology, 71(10), 1616-1625. https://doi.org/10.1002/art.40905

@article{92f61d52736f490398df807389e05db7,

title = "Reducing or Maintaining the Dose of Subcutaneous Tocilizumab in Patients With Rheumatoid Arthritis in Clinical Remission: A Randomized, Open-Label Trial",

abstract = "Objective: To evaluate the efficacy and safety of increasing the dose interval of subcutaneous tocilizumab (TCZ-SC) in patients with rheumatoid arthritis (RA) who are in clinical remission. Methods: RA patients with active disease and an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or to a biologic agent were entered into a single-arm treatment phase with 162 mg of TCZ-SC administered once weekly (TCZ-SC 162 mg qw) as monotherapy or in combination with a csDMARD for 24 weeks. Patients who achieved clinical remission at weeks 20 and 24 were randomized to continue with the same regimen or to switch to 162 mg TCZ-SC administered every 2 weeks (TCZ-SC 162 mg q2w) for 24 weeks (open-label). Patients with a Disease Activity Score in 28 joints (DAS28) of <2.6 were considered to be in clinical remission. Results: In total, 179 (45%) of 401 patients in the single-arm phase achieved clinical remission and were randomized to continue to receive TCZ-SC 162 mg qw (n = 89) or to switch to TCZ-SC 162 mg q2w (n = 90) for 24 weeks. At week 48, significantly more patients treated with TCZ-SC 162 mg qw remained in clinical remission compared to patients who received TCZ-SC 162 mg q2w (90% versus 73%; P = 0.004). The results of other efficacy measures revealed greater efficacy with TCZ-SC 162 mg qw, but none of the efficacy outcomes in this group were significantly different from those in patients treated with TCZ-SC 162 mg q2w, except for the mean change from baseline in the DAS28 score at week 48 (mean change −4.07 points [SD 1.29] versus −3.65 points [SD 1.35]; P = 0.034). Tolerability and safety parameters were similar between the treatment groups. Conclusion: Increasing the dose interval of TCZ-SC in patients with RA was associated with a lower likelihood of maintaining remission after 24 weeks and was not associated with better tolerability. However, most patients were able to sustain remission with a half-dose of TCZ-SC, and therefore this strategy deserves further investigation.",

author = "Raimon Sanmarti and Veale, {Douglas J.} and Emilio Martin-Mola and Alejandro Escudero-Contreras and Carlos Gonz{\'a}lez and Liliana Ercole and Roc{\'i}o Alonso and Fonseca, {Jo{\~a}o E.} and Cristina Alca{\~n}iz and {\'A}lvaro-Gracia, {Jos{\'e} Mar{\'i}a} and Alejandro Balsa and {de Pablos}, {Jos{\'e} Luis} and Miguel, {Consuelo D{\'i}az} and Rodr{\'i}guez, {Jos{\'e} Manuel} and Jose Alves and Elena Aurrecoechea and Jaime Calvo and Joaqu{\'i}n Belzunegui and Francisco Blanco and Rafael Caliz and Javier Calvo and Ivorra, {Jos{\'e} Rom{\'a}n} and Helena Canh{\~a}o and Helena Santos and Eugenio Chamizo and {del Pino}, Javier and Concepci{\'o}n Delgado and C{\'e}sar D{\'i}az and Nebro, {Antonio Fern{\'a}ndez} and Alexander Fraser and Antonio Gomez and Blanca Hern{\'a}ndez and Federico Navarro and Juan Povedano and Mas, {Antonio Juan} and David Kane and Bryan Whelan and Carlos Marras and Juan Moreno and Venegas, {Jos{\'e} P{\'e}rez} and Manuel Pombo and Elena Riera and Antonio Rosas and John Ryan and Jos{\'e} Santos and Maria Santos and Jes{\'u}s Tornero and Tovar, {Juan V{\'i}ctor} and Eduardo Ucar and Carlos Vasconcelos",

year = "2019",

month = oct,

day = "1",

doi = "10.1002/art.40905",

language = "English",

volume = "71",

pages = "1616--1625",

journal = "Arthritis & rheumatology",

issn = "2326-5191",

publisher = "American College of Rheumatology | Wiley",

number = "10",

}

Sanmarti, R, Veale, DJ, Martin-Mola, E, Escudero-Contreras, A, González, C, Ercole, L, Alonso, R, Fonseca, JE, Alcañiz, C, Álvaro-Gracia, JM, Balsa, A, de Pablos, JL, Miguel, CD, Rodríguez, JM, Alves, J, Aurrecoechea, E, Calvo, J, Belzunegui, J, Blanco, F, Caliz, R, Calvo, J, Ivorra, JR, Canhão, H , Santos, H, Chamizo, E, del Pino, J, Delgado, C, Díaz, C, Nebro, AF, Fraser, A, Gomez, A, Hernández, B, Navarro, F, Povedano, J, Mas, AJ, Kane, D, Whelan, B, Marras, C, Moreno, J, Venegas, JP, Pombo, M, Riera, E, Rosas, A, Ryan, J, Santos, J, Santos, M, Tornero, J, Tovar, JV, Ucar, E & Vasconcelos, C 2019, 'Reducing or Maintaining the Dose of Subcutaneous Tocilizumab in Patients With Rheumatoid Arthritis in Clinical Remission: A Randomized, Open-Label Trial', Arthritis & rheumatology, vol. 71, no. 10, pp. 1616-1625. https://doi.org/10.1002/art.40905

TY - JOUR

T1 - Reducing or Maintaining the Dose of Subcutaneous Tocilizumab in Patients With Rheumatoid Arthritis in Clinical Remission

T2 - A Randomized, Open-Label Trial

AU - Sanmarti, Raimon

AU - Veale, Douglas J.

AU - Martin-Mola, Emilio

AU - Escudero-Contreras, Alejandro

AU - González, Carlos

AU - Ercole, Liliana

AU - Alonso, Rocío

AU - Fonseca, João E.

AU - Alcañiz, Cristina

AU - Álvaro-Gracia, José María

AU - Balsa, Alejandro

AU - de Pablos, José Luis

AU - Miguel, Consuelo Díaz

AU - Rodríguez, José Manuel

AU - Alves, Jose

AU - Aurrecoechea, Elena

AU - Calvo, Jaime

AU - Belzunegui, Joaquín

AU - Blanco, Francisco

AU - Caliz, Rafael

AU - Calvo, Javier

AU - Ivorra, José Román

AU - Canhão, Helena

AU - Santos, Helena

AU - Chamizo, Eugenio

AU - del Pino, Javier

AU - Delgado, Concepción

AU - Díaz, César

AU - Nebro, Antonio Fernández

AU - Fraser, Alexander

AU - Gomez, Antonio

AU - Hernández, Blanca

AU - Navarro, Federico

AU - Povedano, Juan

AU - Mas, Antonio Juan

AU - Kane, David

AU - Whelan, Bryan

AU - Marras, Carlos

AU - Moreno, Juan

AU - Venegas, José Pérez

AU - Pombo, Manuel

AU - Riera, Elena

AU - Rosas, Antonio

AU - Ryan, John

AU - Santos, José

AU - Santos, Maria

AU - Tornero, Jesús

AU - Tovar, Juan Víctor

AU - Ucar, Eduardo

AU - Vasconcelos, Carlos

PY - 2019/10/1

Y1 - 2019/10/1

N2 - Objective: To evaluate the efficacy and safety of increasing the dose interval of subcutaneous tocilizumab (TCZ-SC) in patients with rheumatoid arthritis (RA) who are in clinical remission. Methods: RA patients with active disease and an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or to a biologic agent were entered into a single-arm treatment phase with 162 mg of TCZ-SC administered once weekly (TCZ-SC 162 mg qw) as monotherapy or in combination with a csDMARD for 24 weeks. Patients who achieved clinical remission at weeks 20 and 24 were randomized to continue with the same regimen or to switch to 162 mg TCZ-SC administered every 2 weeks (TCZ-SC 162 mg q2w) for 24 weeks (open-label). Patients with a Disease Activity Score in 28 joints (DAS28) of <2.6 were considered to be in clinical remission. Results: In total, 179 (45%) of 401 patients in the single-arm phase achieved clinical remission and were randomized to continue to receive TCZ-SC 162 mg qw (n = 89) or to switch to TCZ-SC 162 mg q2w (n = 90) for 24 weeks. At week 48, significantly more patients treated with TCZ-SC 162 mg qw remained in clinical remission compared to patients who received TCZ-SC 162 mg q2w (90% versus 73%; P = 0.004). The results of other efficacy measures revealed greater efficacy with TCZ-SC 162 mg qw, but none of the efficacy outcomes in this group were significantly different from those in patients treated with TCZ-SC 162 mg q2w, except for the mean change from baseline in the DAS28 score at week 48 (mean change −4.07 points [SD 1.29] versus −3.65 points [SD 1.35]; P = 0.034). Tolerability and safety parameters were similar between the treatment groups. Conclusion: Increasing the dose interval of TCZ-SC in patients with RA was associated with a lower likelihood of maintaining remission after 24 weeks and was not associated with better tolerability. However, most patients were able to sustain remission with a half-dose of TCZ-SC, and therefore this strategy deserves further investigation.

AB - Objective: To evaluate the efficacy and safety of increasing the dose interval of subcutaneous tocilizumab (TCZ-SC) in patients with rheumatoid arthritis (RA) who are in clinical remission. Methods: RA patients with active disease and an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or to a biologic agent were entered into a single-arm treatment phase with 162 mg of TCZ-SC administered once weekly (TCZ-SC 162 mg qw) as monotherapy or in combination with a csDMARD for 24 weeks. Patients who achieved clinical remission at weeks 20 and 24 were randomized to continue with the same regimen or to switch to 162 mg TCZ-SC administered every 2 weeks (TCZ-SC 162 mg q2w) for 24 weeks (open-label). Patients with a Disease Activity Score in 28 joints (DAS28) of <2.6 were considered to be in clinical remission. Results: In total, 179 (45%) of 401 patients in the single-arm phase achieved clinical remission and were randomized to continue to receive TCZ-SC 162 mg qw (n = 89) or to switch to TCZ-SC 162 mg q2w (n = 90) for 24 weeks. At week 48, significantly more patients treated with TCZ-SC 162 mg qw remained in clinical remission compared to patients who received TCZ-SC 162 mg q2w (90% versus 73%; P = 0.004). The results of other efficacy measures revealed greater efficacy with TCZ-SC 162 mg qw, but none of the efficacy outcomes in this group were significantly different from those in patients treated with TCZ-SC 162 mg q2w, except for the mean change from baseline in the DAS28 score at week 48 (mean change −4.07 points [SD 1.29] versus −3.65 points [SD 1.35]; P = 0.034). Tolerability and safety parameters were similar between the treatment groups. Conclusion: Increasing the dose interval of TCZ-SC in patients with RA was associated with a lower likelihood of maintaining remission after 24 weeks and was not associated with better tolerability. However, most patients were able to sustain remission with a half-dose of TCZ-SC, and therefore this strategy deserves further investigation.

UR - http://www.scopus.com/inward/record.url?scp=85067626906&partnerID=8YFLogxK

U2 - 10.1002/art.40905

DO - 10.1002/art.40905

M3 - Article

C2 - 31087542

AN - SCOPUS:85067626906

VL - 71

SP - 1616

EP - 1625

JO - Arthritis & rheumatology

JF - Arthritis & rheumatology

SN - 2326-5191

IS - 10

ER -

Reducing or Maintaining the Dose of Subcutaneous Tocilizumab in Patients With Rheumatoid Arthritis in Clinical Remission: A Randomized, Open-Label Trial

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