Methotrexate and Gold Study

A 48-Week Randomized Double-Blind Double-Observer Placebo Controlled Multicentre Trial Of Combination Methotrexate And Intramuscular Gold In Rheumatoid Arthritis: Results of The METGO Study

Introduction:

This study was done to evaluate how safe adding injections (shots) of a gold drug (gold sodium thioglucose) is in persons with rheumatoid arthritis, and whether their arthritis gets a lot better. The study was done in people who were already taking the standard drug to control rheumatoid arthritis, methotrexate, but who had not had got completely better.

A combination of two or more medications is becoming more common, as this often controls rheumatoid arthritis better and prevents joint damage better than one drug alone. Methotrexate is now combined with other Disease Modifying Anti-Rheumatic Drugs (DMARDs). Some of the DMARDs used with methotrexate include:

Hydroxychloroquine
Sulfasalazine
Cyclosporine
Leflunomide (Arava)
Infliximab (Remicade)
Etanercept (Enbrel)
Adalimumab (Humira)

Gold was the first DMARD ever shown to reduce joint damage from rheumatoid arthritis. There was evidence gold might work well with methotrexate but a definitive study was needed to learn if adding gold to methotrexate would be safe and would make a difference to people with rheumatoid arthritis.

Project Methodology:

Sixty-five people from 13 centres across Canada received either a gold shot or placebo injections added to their regular methotrexate treatment weekly for 48 weeks. Neither the participant nor the study team knew whether they received gold or placebo.

A lot of information was collected on everyone. Participants completed questionnaires assessing their quality of life, pain and how disabled they were at the beginning of the study and at 12, 24, 36, and 48 weeks after their first shot. The number of inflamed joints were counted and blood tests to assess the arthritis were also done.

Participant Recruitment:

People with rheumatoid arthritis for less than 10 years who had never had gold shots before could join the study. Participants came from arthritis clinics across Canada - Vancouver, Penticton, Edmonton, Saskatoon, Winnipeg, London, Toronto, Mississauga, Montreal, and St. John. The study was coordinated in Vancouver at the Arthritis Research Centre of Canada.

Relevance For People With Arthritis:

This is the first highly scientific study to show that gold shots can be added to methotrexate in people with rheumatoid arthritis and improve them. In fact, the gold shots increased a person's chance of improvement by more than 300%. Gold reduces the number of inflamed joints, the level of pain, the amount of disability and it improves the quality of life. Even better, using gold like this not only makes people with rheumatoid arthritis better, it saves money.

Results:

The people who received gold shots were over 300% more likely to achieve important improvement in their health after 48 weeks than people who had placebo shots. Improvement was measured using a standard measure that combines inflammation, pain, disability, and how a person feels (called the ACR-20).

A surprising finding was that money was saved when gold was used. The extra costs of the gold shots saved money because the person getting the shot was so much better off that it paid for the gold shots.

Side effects were much more common on gold than placebo (58% vs. 22%). This was expected as gold is known to cause side-effects. Most side-effects were skin rash or skin itch and these tended to disappear even though the gold was continued. Only 11% of the gold group had to stop the gold for good because of side-effects. When people discontinued the gold, the side effects went away.

Consumer Involvement:

A Safety Committee of four people regularly reviewed the information from the study to make certain that the study rules were being followed and to check that the study was safe for the people in the study. Three of the four were from the USA. One of the four, and the only Canadian, was a consumer (in this case a person with rheumatoid arthritis).

Time Frame:

Participants were recruited for the study between 1998 and 2001. The study was completed in 2002.

Funding Agency:

Funding for the study was received from the Canadian Institutes of Health Research (previously the Medical Research Council of Canada) and The Arthritis Society of Canada. Several of the study sites received additional funding - this included support from the Alberta Division of The Arthritis Society of Canada ; the Edmonton Arthritis Association; the Royal Alexandra Hospital Foundation; and, the Penticton Regional Hospital Research Fund. Sanofi Canada provided the study drug at no charge.

Publications / Presentations

Lehman AJ, Esdaile JM, Klinkhoff A, Grant E, Fitzgerald A, Canvin, J., The METGO Study Group. A 48-week, randomized, double-blind, double-observer, placebo-controlled multicenter trial of combination methotrexate and intramuscular gold therapy in rheumatoid arthritis: Results of The METGO Study. Arthritis and Rheumatism 2005;52:1360-1370.

Project Team Members:

Principal Investigator

John M. Esdaile MD, FRCPC, MPH
Scientific Director, ARC

Co-Investigators

Alice Klinkhoff MD
UBC, Mary Pack Arthritis Centre

Diane Lacaille MD, MHSc
Research Scientist, ARC

Michael Schulzer MD, PhD
UBC

Eric Grant; Eva Sadowska
St. John, NB

Avril Fitzgerald; Dale Sholter; Sharon Leclerq
Edmonton, AB

Janice Canvin; Christine Peschken
Winnipeg, MB

William Bensen
Hamilton, ON

Michel Zummer; Pierre Dagenais; Mary-Ann Fitzcharles; Susan Joseph; Ann E Clarke
Montreal, QC

Manfred Harth; John Thompson; Janet Pope
London, ON

Robert Offer; Stuart Kircher
Penticton, BC

Edward Keystone; Vivian Bykerk
Toronto, ON

Jacqueline Stewart
Mississauga, ON

John Sibley; Bin Liu
Saskatoon, SK
Nurse Coordinators

Karen Rangno
Senior Clinical Trials Nurse, ARC Terry Viczko (ARC)

Dianne Grant (St. John)
Edna Hutchings (Edmonton)
Donna Hart (Winnipeg)
Helena Ross (Hamilton)
Lise Lauzon (Montreal)
Lynda Bere (London)
Susan Offer (Penticton)
Deborah Weber (Toronto)
Karen Leblanc (Mississauga)
Lilian Urroz (Saskatoon)
Beverley Rowat (Montreal)

Study Coordinator

Allen Lehman MA, PhD
Research Associate, ARC