An open-label study assessing the addition of subcutaneous golimumab (GLM) to conventional disease-modifying antirheumatic drug (DMARD) therapy in biologic-naïve subjects with rheumatoid arthritis (Part 1), followed by a randomized study assessing the value of combined intravenous and subcutaneous GLM administration aimed at inducing and maintaining remission (Part 2).

Golimumab (GLM) is a fully human anti-TNF-alfa monoclonal antibody that is
administered subcutaneously once monthly.
GLM (50 mg, SC) has been registered by the European Authorities on October, 1st
2009.
The knowledge related to the safety profile of GLM can change over time through
expanded use in terms of patient characteristics and the number of patients
exposed. As a lot new agents, upon introduction to the market, have usually
been studied only in a limited number of highly selcted patient patient
populations, it is important to continue to investigate and document the
safety and effectiveness of GLM, aiming at increasing the knowledge base of GLM
in the daily clinical practice setting.

Part 1: To assess the safety and effectiveness of subcutaneous golimumab 50 mg
(SC-GLM50), administered by autoinjection once monthly during 6 months, when
combined with different DMARD regimens used in daily rheumatology.

Part 2: In subjects who have responded to the treatment administered in part 1
(i.e., from baseline to the end of month 6( but have not achieved remission at
the end of month 6, to stud ywhether a strategy of using intravenous golimumab
at 2 mg/kg body weight (IV-GLM2) to induce remission, followed by SC-GLM50 to
retain remission, is superior to continuing a SC-GLM50 regimen.

This is an open-label, multinational, multicenter, prospective trial of GLM in
biologic-naive subjects with RA who have active disease despite taking a
conventional DMARD regiman.
In total approximately 3150 patients will participate in part 1 of the study
and approximately 500 patients in part 2 of the study.

Part 1: subjects will be asked to continue their DMARD regimen under wich their
disease is not sufficiently controlled and will receive subcutaneous GLM (50
mg) by autoinjection once monthly.
Patients will be treated during 6 months (i.e. a total of six doses), for which
they will have to visit the hospital 5 times.
During these visits physical examination (including bloodpressure and
heartrate) and RA specific assessments (TJC28 and SJC28) will be performed,
blood samples taken (clinical chemistry, hematology, ESR, RA and inflammatory
factors) and questionnaires completed (HAQ, EQ-5D and evaluation of the
patients regarding illness and treatment).

Patients who only participate in part 1 of the trial (they are not eligible for
part 2 of the trial, or enrollment in part 2 may already been closed) and live
in a country where GLM is commercially available and reimburable, the subject
will end his/her participation in the trial at the end of month 6.
In case GLM is not (yet) available and the investigator feels the subject would
benefit from continued GLM use, then the sponsor will provide GLM free of
charge for an additional 6 months (part 1 extension phase). The subject will
attend a final visit for safety follow up at the end of month 12.

Part 2: subjects who responded to treatment but are not in remission at the end
of part 1 will be randomized in a 1:1 ration to one of the two treatment arms.
- Arm 1 (strategy arm): IV-GLM2 (2mg / kg) will be infused to each subject at
the start of month 7, then at the start of month 8 and 10, if the subject has
not achieved remission at any of these infusion visits. If a subject is found
to be in remission at the time of an infusion visit after month 7, that
subject will receive a subcutaneous GLM (50 mg) injection, and the monthly
SC-GLM50 regimen will continue until the end of month 12 unless the subject is
found to have flared (i.e. remission was not retained) at the start of month
10. In this case the subject will receive an IV-GLM2 infusion at the start of
month 10; SC-GLM50 injections will be resumed at the start of month 11 and
continued until the end of month 12.
- Arm 2 (reference arm): the monthly SC-GLM50 regimen will be continued from
the start of month 7 through the end of month 12

In this period the subject will have 6 study related visits, during which
physical examination (including bloodpressure and heartrate) and RA specific
assessments (TJC68 and SJC66) will be performed, blood samples taken (clinical
chemistry, hematology, ESR, inflammatory factors) and questionnaires completed
(HAQ, EQ-5D and evaluation of the patients regarding illness and treatment).

During part 1 of the study golimumab will be injected once a month (50 mg)
using a autoinjector. Subjects who are eligible for the extension of part 1
will be treated for an additional 6 months with SC-GLM50.

Subjects who are eligible for part 2 of the trial and are randomized to the IV
arm are infused with IV-GLM 2 on month 7, 8 and 10, unless the patient is found
in remission during one of the infusion visits. In that case the patient will
be further treated once a month with subcetaneous GLM until month 12. In case
of a flare the patient can be switched to the IV regimen again until month 10.
Patients in the reference arm will be injected with SC-GLM50 on a monthly base
for 6 months.

The burden for trial subjects consists of administration of GLM by means of an
autoinjector or infustion (part 2).
The SC injections with the autoinjector and/or the infusion of GLM could lead
to occurence of an injection- or infusion reaction.

Further burden for the trial subjects consists of regular visits to the
hospital (max. 6 visits in part 1 as well as in part 2), including
venapunctures, short not extended (physical examination), RA specific
assessments and the completion of questionnaires.
The most important risks for the subjects are the side effects, caused by the
study medication, as described in the Investigator's Brochure version May 2009.

The most common side effects, caused by the use of GLM, are the subject's
higher susceptibility for infections or worsening of existing infections. Also
hypertension is a common side effect of GLM use.