Infliximab therapy increases body fat mass in early rheumatoid arthritis independently of changes in disease activity and levels of leptin and adiponectin: a randomised study over 21 months.
BACKGROUND
Rheumatoid arthritis (RA) is associated with changes in body composition and bone mineral density (BMD). The purpose of the present study was to evaluate whether anti-TNF treatment in early RA has an impact on body composition and BMD besides that which could be achieved by intensive disease-modifying anti-rheumatic drug (DMARD) combination therapy.


METHODS
Forty patients with early RA who failed treatment with methotrexate up to 20 mg/week for 3 months were randomised to addition of sulphasalazine and hydroxychloroquine (treatment A) or addition of infliximab (treatment B). At 3, 12 and 24 months, body composition and BMD were assessed by total-body dual-energy X-ray absorptiometry. At the same time points, leptin, adiponectin, apolipoproteins, insulin-like growth factor-1 (IGF-1) and markers of bone remodelling were analysed. Compliance to treatment was considered in the analyses. Data were analysed with a mixed, linear model.


RESULTS
Patients treated with anti-TNF had a significant increase in fat mass at 2 years, 3.8 (1.6 to 5.9) kg, in contrast to patients in treatment A, 0.4 (-1.5 to 2.2) kg (P = 0.040), despite similar reduction in disease activity. Both treatment strategies prevented loss of muscle mass and bone. Leptin concentrations increased significantly in both groups at 2 years and adiponectin increased significantly at 2 years in treatment A and at 1 year in treatment B. There were no significant changes in apolipoproteins or IGF-1. The markers of bone resorption decreased at 12 months in both treatment groups with no significant difference between the treatment groups.


CONCLUSIONS
Infliximab therapy increased body fat mass, an effect that was not achieved with the combination of DMARDs, despite a similar reduction in disease activity, and thus seemed to be drug specific. The increase of fat mass was not associated with an exacerbated atherogenic lipid profile. Leptin and adiponectin concentrations increased in both treatment groups. The increase of adiponectin may partially explain the reduced frequency of cardiovascular diseases found when disease activity is reduced in RA.


BACKGROUND
ISRCTN39045408.
Engvall
Inga-Lill
IL
Department of Rheumatology, Karolinska Institutet at Karolinska University Hospital Huddinge, R92, Stockholm 141 86, Sweden. inga-lill.engvall@karolinska.se
Tengstrand
Birgitta
B
Brismar
Kerstin
K
Hafström
Ingiäld
I
D015502:Absorptiometry, Photon; D052242:Adiponectin / Q000097:blood; D000273:Adipose Tissue / Q000187:drug effects*; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001053:Apolipoproteins / Q000097:blood; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy*; D001823:Body Composition / Q000187:drug effects*; D015519:Bone Density / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects; D005260:Female; D006801:Humans; D006886:Hydroxychloroquine / Q000008:administration & dosage; D000069285:Infliximab; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D020738:Leptin / Q000097:blood; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D011863:Radioimmunoassay; D012460:Sulfasalazine / Q000008:administration & dosage
D052242:Adiponectin; D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D001053:Apolipoproteins; D020738:Leptin; D012460:Sulfasalazine; D006886:Hydroxychloroquine; D007334:Insulin-Like Growth Factor I; D000069285:Infliximab; D008727:Methotrexate