Clinical trial NCT00209859: Methotrexate and Cyclosporine in Treatment of Early Rheumatoid Arthritis
Official title: Combination Treatment With Methotrexate and Cyclosporine in Early Rheumatoid Arthritis.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Rheumatoid Arthritis
Lead sponsor: Hvidovre University Hospital
Sponsor class: OTHER
First posted: 2005-09-21
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To investigate whether cyclosporine, added to methotrexate and steroid, increases the possibility of inflammatory management early in the disease; furthermore to investigate the possible steroid-sparing effect of cyclosporine in patients with recently diagnosed rheumatoid arthritis.

Detailed description: Design: Multicentre, prospective, randomised, double-blind study with parallel design.

Selection of patients: Patients with recently diagnosed rheumatoid arthritis (less than 6 months of persistent synovitis).

Eligibility criteria: Inclusion Criteria:

* Synovitis in at least 2 joints.
* Compliance with the ACR criteria for RA.
* Duration of no more than 6 months (from the first anamnestic non-traumatic synovitis of at least 6 weeks' duration).
* Informed consent.

Exclusion Criteria:

* Age less than 18 years or more than 75 years
* Lack of co-operability.
* Previous treatment with DMARD
* Corticosteroid treatment during the preceding 4 weeks.
* Contra indications for the treatments (awaiting the recommendations from Novartis)
* Previous or present malignant or premalignant disease
* Poorly regulated hypertension
* Impaired renal function
* Immuno defective diseases, including HIV
* Cardiac or pulmonary insufficiency
* Serious arteriosclerosis
* Serious granulocytopenia or thrombocytopenia
* Impaired liver function (liver enzymes more than twice the highest normal limit).
* Alcohol consumption of more than 3 drinks a week.
* Poorly controlled epilepsy
* Lack of contraception in fertile patients
* Pregnancy and lactation
* Psoriasis
* Poorly regulated diabetes
* Anticoagulant treatment
* Known allergy to the medicine
* Medicamental interactions
* Other inflammatory rheumatic diseases

Primary outcomes:
measure: ACR20 response
Secondary outcomes:
measure: ACR remission (modified)
measure: Cumulated dose of glucocorticoids
measure: Development of erosions
measure: Development of osteopenia
Other outcomes:
Locations:
city: Hvidovre
country: Denmark
facility: Hvidovre University Hospital
Study officials:
affiliation: Hvidovre Univervsity Hospital
name: Merete L Hetland, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rheumatism Hospital Graasten
name: Kim Hørslev-Petersen, MD, DSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Herly M, Stengaard-Pedersen K, Vestergaard P, Ostergaard M, Junker P, Hetland ML, Horslev-Petersen K, Ellingsen T. The D-vitamin metabolite 1,25(OH)2 D in serum is associated with disease activity and Anti-Citrullinated Protein Antibodies in active and treatment naive, early Rheumatoid Arthritis Patients. Scand J Immunol. 2018 Sep;88(3):e12704. doi: 10.1111/sji.12704. Epub 2018 Aug 22.
citation: Herly M, Stengaard-Pedersen K, Horslev-Petersen K, Hetland ML, Ostergaard M, Christensen R, Logstrup BB, Vestergaard P, Podenphant J, Junker P, Ellingsen T. Association between baseline vitamin D metabolite levels and long-term cardiovascular events in patients with rheumatoid arthritis from the CIMESTRA trial: protocol for a cohort study with patient-record evaluated outcomes. BMJ Open. 2017 Apr 8;7(4):e014816. doi: 10.1136/bmjopen-2016-014816.
citation: Hetland ML, Ostergaard M, Ejbjerg B, Jacobsen S, Stengaard-Pedersen K, Junker P, Lottenburger T, Hansen I, Andersen LS, Tarp U, Svendsen A, Pedersen JK, Skjodt H, Ellingsen T, Lindegaard H, Podenphant J, Horslev-Petersen K; CIMESTRA study group. Short- and long-term efficacy of intra-articular injections with betamethasone as part of a treat-to-target strategy in early rheumatoid arthritis: impact of joint area, repeated injections, MRI findings, anti-CCP, IgM-RF and CRP. Ann Rheum Dis. 2012 Jun;71(6):851-6. doi: 10.1136/annrheumdis-2011-200632. Epub 2012 Feb 1.
citation: Christensen AF, Horslev-Petersen K, Christgau S, Lindegaard HM, Lottenburger T, Junker K, Hetland ML, Stengaard-Pedersen K, Jacobsen S, Ellingsen T, Andersen LS, Hansen I, Skjodt H, Pedersen JK, Lauridsen UB, Svendsen AJ, Tarp U, Podenphant J, Heegaard NH, Vestergaard A, Jurik AG, Ostergaard M, Junker P. Uncoupling of collagen II metabolism in newly diagnosed, untreated rheumatoid arthritis is linked to inflammation and antibodies against cyclic citrullinated peptides. J Rheumatol. 2010 Jun;37(6):1113-20. doi: 10.3899/jrheum.091265. Epub 2010 May 1.
citation: Christensen AF, Sorensen GL, Horslev-Petersen K, Holmskov U, Lindegaard HM, Junker K, Hetland ML, Stengaard-Pedersen K, Jacobsen S, Lottenburger T, Ellingsen T, Andersen LS, Hansen I, Skjodt H, Pedersen JK, Lauridsen UB, Svendsen A, Tarp U, Podenphant J, Vestergaard A, Jurik AG, Ostergaard M, Junker P. Circulating surfactant protein -D is low and correlates negatively with systemic inflammation in early, untreated rheumatoid arthritis. Arthritis Res Ther. 2010;12(2):R39. doi: 10.1186/ar2948. Epub 2010 Mar 8.
citation: Hetland ML, Ejbjerg B, Horslev-Petersen K, Jacobsen S, Vestergaard A, Jurik AG, Stengaard-Pedersen K, Junker P, Lottenburger T, Hansen I, Andersen LS, Tarp U, Skjodt H, Pedersen JK, Majgaard O, Svendsen AJ, Ellingsen T, Lindegaard H, Christensen AF, Vallo J, Torfing T, Narvestad E, Thomsen HS, Ostergaard M; CIMESTRA study group. MRI bone oedema is the strongest predictor of subsequent radiographic progression in early rheumatoid arthritis. Results from a 2-year randomised controlled trial (CIMESTRA). Ann Rheum Dis. 2009 Mar;68(3):384-90. doi: 10.1136/ard.2008.088245. Epub 2008 Apr 3.