A Study to Assess the Effect of Tocilizumab + Methotrexate on Signs and Symptoms in Patients With Moderate to Severe Active Rheumatoid Arthritis Currently on Methotrexate Therapy

Conditions

Rheumatoid Arthritis

Brief summary

This 3 arm study will compare the safety and efficacy, with regard to reduction of signs and symptoms, of tocilizumab versus placebo in combination with methotrexate (MTX) in patients with moderate to severe active rheumatoid arthritis (RA) currently on MTX therapy, and who have had an inadequate response to prior therapy with an anti-tumor necrosis factor (anti-TNF) agent. Patients will be randomized to receive tocilizumab 4mg/kg iv, tocilizumab 8mg/kg or placebo iv, every 4 weeks. All patients will also receive methotrexate 10-25mg/week. The anticipated time on study treatment is 3-12 months, and the target sample size is 500+ individuals.

Schmitt C, Brockwell L, Giraudon M, Zucchetto M, Christ L, Bannert B, Daikeler T, Villiger PM.

2022-06-047 citations

10.1186/s13075-022-02815-9

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Impact of tocilizumab administered intravenously or subcutaneously on patient-reported quality-of-life outcomes in patients with rheumatoid arthritis.

Strand V, Michalska M, Birchwood C, Pei J, Tuckwell K, Finch R, Kivitz AJ, Smolen JS, Burmester GR.

2018-06-1712 citations

10.1136/rmdopen-2017-000602

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RMD Open2018-03-0130 citations

10.1136/rmdopen-2017-000607

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Vieira MC, Zwillich SH, Jansen JP, Smiechowski B, Spurden D, Wallenstein GV.

2016-11-2436 citations

10.1016/j.clinthera.2016.11.004

Early changes in blood-based joint tissue destruction biomarkers are predictive of response to tocilizumab in the LITHE study.

Bay-Jensen AC, Platt A, Siebuhr AS, Christiansen C, Byrjalsen I, Karsdal MA.

2016-01-2029 citations

10.1186/s13075-015-0913-x

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Edward Keystone, Andrew M. Anisfeld, Sarika Ogale, Jenny Devenport, Jeffrey R. Curtis

The Journal of Rheumatology2014-01-159 citations

10.3899/jrheum.130489

Improvements in health-related quality of life after treatment with tocilizumab in patients with rheumatoid arthritis refractory to tumour necrosis factor inhibitors: results from the 24-week randomized controlled RADIATE study.

Strand V, Burmester GR, Ogale S, Devenport J, John A, Emery P.

2012-06-2875 citations

10.1093/rheumatology/kes131

IL-6 receptor inhibition positively modulates bone balance in rheumatoid arthritis patients with an inadequate response to anti-tumor necrosis factor therapy: biochemical marker analysis of bone metabolism in the tocilizumab RADIATE study (NCT00106522).

Karsdal MA, Schett G, Emery P, Harari O, Byrjalsen I, Kenwright A, Bay-Jensen AC, Platt A.

2012-03-0674 citations

10.1016/j.semarthrit.2012.01.004

IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals: results from a 24-week multicentre randomised placebo-controlled trial.

Emery P, Keystone E, Tony HP, Cantagrel A, van Vollenhoven R, Sanchez A, Alecock E, Lee J, Kremer J.

2008-07-14797 citations

10.1136/ard.2008.092932

Interventions

DRUGMethotrexate

10-25mg weekly

DRUGPlacebo

iv every 4 weeks

DRUGtocilizumab [RoActemra/Actemra]

8mg/kg iv every 4 weeks

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

Inclusion criteria

* adult patients at least 18 years of age with moderate to severe active RA for at least 6 months; * inadequate response to current anti-rheumatic therapies, including MTX; * inadequate response or intolerance to treatment with 1 or more anti-TNF therapies within 1 year of entering study; * on stable MTX for at least 8 weeks before entering study; * patients of reproductive potential must be using reliable methods of contraception.

Exclusion criteria

* major surgery (including joint surgery) within 8 weeks before screening, or planned major surgery within 6 months after entering study; * women who are pregnant or breast-feeding.

Design outcomes

Primary

Measure	Time frame
Percentage of patients with ACR 20 response	Week 24
AEs, laboratory parameters, vital signs, ECGs.	Throughout study

Secondary

Measure	Time frame
Percentage of patients with ACR 50 and ACR 70 responses	Week 24
Mean changes in parameters of ACR core set	Week 24

Countries

Australia, Belgium, Canada, France, Germany, Iceland, Italy, Mexico, Netherlands, Puerto Rico, Sweden, Switzerland, United Kingdom, United States

Outcome results

None listed