Initial Treatment With Golimumab in Early PsA

A Randomized, Double-blind, Placebo-controlled Trial of Golimumab+Methotrexate Versus Methotrexate Alone in Methotrexate-naïve Patients With Psoriatic Arthritis

The investigators will perform a 22-week randomized, double-blind, placebo-controlled trial of golimumab + methotrexate (MTX) versus methotrexate alone in methotrexate-naïve patients with Psoriatic Arthritis (PsA). Afterwards, a 28 week open label phase with methotrexate alone is started. Golimumab will be discontinued.

Hypotheses:

First, the investigators hypothesize that initiation of a combination therapy with golimumab + MTX will be safe and superior to MTX alone in MTX-naïve PsA patients, as assessed by the percentage of patients achieving Disease Activity Score (the investigators hypothesize that more patients with the early combination treatment will respond (according to Disease Activity Score (DAS), American college of Rheumatology (ACR), or Psoriatic Arthritis Response Criteria (PsARC) responses) and achieve a state of Low Disease Activity (LDA) or Minimal Disease Activity (MDA) than patients on MTX alone.

Third, the investigators hypothesize that a significant proportion of the patients will continue to benefit from this early aggressive treatment initiation even after stopping golimumab treatment.

Study Overview

• Status: Completed
• Conditions: Psoriatic Arthritis
• Intervention / Treatment: Drug: methotrexate; Drug: golimumab

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 3

Contacts and Locations

Study Locations

• Netherlands
  • Noord Holland
    • Amsterdam, Noord Holland, Netherlands, 1056 AB
      • Reade
    • Amsterdam, Noord Holland, Netherlands, 1105 AZ
      • Academic Medical Center/University of Amsterdam

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Prior to any study procedure, voluntary written informed consent must be obtained, after the nature and purpose of this study were explained
• Patients should be between 18 and 70 years of age at time of consent
• Patients must have a diagnosis of PsA according to the Classification for psoriatic Arthritis (CASPAR) classification criteria (see Appendix 1).
• The patient must have an active disease as defined by 3 swollen and 3 tender joints.
• The use of a stable dose of concomitant nonsteroidal antiinflammatory drug (NSAIDs) and/or corticosteroids is allowed. The dose of corticosteroids should not exceed a prednisone equivalent of 10 mg/day and must be stable for at least 4 weeks prior to baseline. The dose of concomitant NSAIDs and corticosteroids should be kept stable during the whole study period.
• Patients are considered to be in generally good health based upon the result of a medical history, physical examination, laboratory profile, chest X-ray and electrocardiography (ECG).

Exclusion Criteria:

• Patient has a concomitant rheumatic condition other than PsA
• Positivity for rheumatoid factor (RF) or anti-cyclic citrullinated peptide (anti CCP) antibodies (ACPA)
• Current or previous use of methotrexate
• Current use of other Disease Modifying Antirheumatic drug (DMARDs) (sulphasalazine or leflunomide).
• Prior use of other DMARDs (sulphasalazine or leflunomide) within 3 months before baseline.
• Current or previous use of biologicals, including Tumor Necrosis Factor (TNF) blocking therapy
• Patient has active tuberculosis. A purified protein derivative (PPD) skin test and chest X-ray at screening should be negative (in case of latent tuberculosis, a patient may enter the study if prophylaxis with isoniazide is begun prior to administration of study medication). If a patient has an adequately treated tuberculosis in the past, he/she may enter the trial.
• Patient has received an intra-articular injection with corticosteroids within 4 weeks prior to baseline.
• Patient has a malignancy (other than basal cell carcinoma of the skin) in the past 5 years
• Patients has a recent history of (or persistent) infection requiring hospitalization or antibiotic treatment within 4 weeks of baseline Patient has a significant history of cardiac, pulmonary, renal (glomerular filtration rate <40ml/min), hepatic (liver cirrhosis), hematological, neurological, metabolic or any other disease that may affect his/her participation in this study. This should be decided by the opinion of the investigator.
• All females of childbearing potential must use appropriate contraception, be postmenopausal or surgically sterile. A urine pregnancy-test beta-human chorion gonadotropin (Beta-HCG) will be performed at screening and has to be negative.
• Subject is pregnant or a breastfeeding woman
• Liver disease or liver injury as indicated by abnormal liver function tests such as Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), gammaglutamyl transpeptidase (GGT), alkaline phosphatase, or serum bilirubin. The Investigator should be guided by the following criteria: Any single parameter may not exceed 2 x upper limit of normal (ULN).

A single parameter elevated up to and including 2 x ULN should be rechecked once more if elevation levels are found clinically relevant according to the physician, at least prior to enrolment.

- Patient is, in the opinion of the investigator, unable to comply with the requirements of the study protocol or is unsuitable for the study for any reason.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: methotrexate; methotrexate is the active comparator, it will be compared to golimumab + methotrexate	Drug: methotrexate; Methotrexate will be started at a dosage of 15 mg/week orally and, if well tolerated, increased to 20mg/week at week 4 and 25mg/week at week 8 of the trial. If well tolerated, the maximum dose of 25 mg/week will be sustained until end of study (week 50). Folic acid 5 mg/week will be administered orally one day after the MTX intake.
Experimental: golimumab and methotrexate; The combination of golimumab en methotrexate will be compared to methotrexate alone.	Drug: golimumab; golimumab 50mg subcutaneous injections (in combination with methotrexate), once a month, for a period of 22 weeks; Other Names: simponi

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients achieving DAS remission response criteria	1. To demonstrate that golimumab + MTX is superior to MTX alone in achieving DAS remission in MTX naïve PsA patients at week 22 DAS = Disease activity score, remission is defined as a DAS < 1.6	week 22
Number of Participants with Adverse Events	Number of patients with(severe) adverse events (and type) during the study period. Safety will be monitored during the study period by laboratory tests and physical examination.	week 22

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients fulfilling Minimal Disease activity criteria and other outcome measurements	To demonstrate that golimumab + MTX is superior to MTX alone as assessed by DAS, ACR and PsARC responses, as well as by achievement of low disease activity (LDA, as defined by DAS<2.4) and minimal disease activity (MDA, as defined by Coates et al, Ann Rheum Dis 2010). Also the Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) score and Psoriasis Area Severity Index (PASI) score will be determined in MTX naïve PsA patients at week 22.	week 22

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy after withdrawing anti-TNF	To demonstrate that initial treatment of MTX naïve patients with golimumab + MTX is superior to MTX alone to maintain DAS (disease activity score) remission, LDA (Low Disease Activity) and MDA over time (up to week 50) after withdrawing golimumab.	week 50

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Investigators: Principal Investigator: Dominique LP Baeten, Prof. dr. MD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Publications and helpful links

General Publications

• de Jong HMY, van Mens LJJ, Nurmohamed MT, Kok MR, van Kuijk AWR, Baeten DLP, van de Sande MGH. Sustained remission with methotrexate monotherapy after 22-week induction treatment with TNF-alpha inhibitor and methotrexate in early psoriatic arthritis: an open-label extension of a randomized placebo-controlled trial. Arthritis Res Ther. 2019 Sep 14;21(1):208. doi: 10.1186/s13075-019-1998-4.
• van Mens LJJ, de Jong HM, Fluri I, Nurmohamed MT, van de Sande MGH, Kok M, van Kuijk AWR, Baeten D. Achieving remission in psoriatic arthritis by early initiation of TNF inhibition: a double-blind, randomised, placebo-controlled trial of golimumab plus methotrexate versus placebo plus methotrexate. Ann Rheum Dis. 2019 May;78(5):610-616. doi: 10.1136/annrheumdis-2018-214746. Epub 2019 Feb 26.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2013
• Primary Completion (Actual): November 1, 2018
• Study Completion (Actual): November 1, 2018

Study Registration Dates

• First Submitted: January 7, 2013
• First Submitted That Met QC Criteria: June 4, 2013
• First Posted (Estimate): June 7, 2013

Study Record Updates

• Last Update Posted (Actual): November 26, 2018
• Last Update Submitted That Met QC Criteria: November 22, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: safety; methotrexate; psoriatic arthritis; withdrawal; golimumab; minimal disease activity
• Additional Relevant MeSH Terms: Skin Diseases; Joint Diseases; Musculoskeletal Diseases; Skin Diseases, Papulosquamous; Spinal Diseases; Bone Diseases; Spondylarthropathies; Spondylarthritis; Spondylitis; Psoriasis; Arthritis; Arthritis, Psoriatic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Tumor Necrosis Factor Inhibitors; Methotrexate; Golimumab
• Other Study ID Numbers: AMC_ 42670_PsA_Golimumab