Effects of the anti-interleukin-6 receptor antibody, tocilizumab, on serum lipid levels in patients with rheumatoid arthritis

Abstract

We investigated the effects of anti-IL-6 receptor antibody, tocilizumab (TCZ), on lipid metabolism. Nineteen patients with rheumatoid arthritis (RA), entered in clinical case-control study of SAMURAI trial at Sasebo Chuo Hospital, were examined. Nine patients received TCZ monotherapy at 8 mg/kg intravenously every 4 weeks (TCZ group) and 10 patients received conventional DMARDs (control group). Serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), apolipoprotein (Apo) A-1, Apo A-2 and Apo B as well as disease activity score (DAS), C-reactive protein and serum amyloid A protein were examined at baseline and after 3 months of the treatment. IL-6 inversely was correlated with LDL, Apo A-1 and Apo A-2, and also tended to correlate with Apo B. In TCZ group, serum levels of TC, HDL, LDL, Apo A-1 and Apo A-2 were significantly increased after 3 months treatment with TCZ. There was no significant change in Apo B, the atherogenic index, and TC/HDL by the TCZ treatment. Changes in the DAS28-ESR negatively correlated with those in TC. In one patient, whose serum level of TCZ was not detected after 3 months of the treatment, the absence of the increment in serum levels of Apo A-1 and A-2 in the patient was remarkable. All of the markers did not change during 3 months in control group. These data may raise an important issue to evaluate the impact of these alternations in lipid metabolism for longer periods in RA patients treated with TCZ.

Efficacy and Safety of Baricitinib in Japanese Patients with Active Rheumatoid Arthritis Receiving Background Methotrexate Therapy: A 12-week, Double-blind, Randomized Placebo-controlled Study

“…Increases in CPK were not associated with adverse events consistent with muscle injury or myositis. In addition, LDL cholesterol and HDL cholesterol increased in a dose-dependent fashion, which is consistent with studies of other therapies that inhibit JAK or IL-6 activity 25,26,27 . The longterm effect of baricitinib on lipid metabolism and the effect on the cardiovascular system needs careful evaluation in future studies.…”

Interleukin-6 Protects Human Macrophages from Cellular Cholesterol Accumulation and Attenuates the Proinflammatory Response

“…Indeed, it is noteworthy that IL-6 Ϫ/Ϫ mice developed matureonset obesity and glucose intolerance (54), a result that is consistent with the observation that the treatment of Castleman disease patients with tocilizumab, a humanized IL-6 receptorinhibiting monoclonal antibody, led to an increase of body weight in addition to hypertriglyceridemia (55). Moreover, the regulatory action of IL-6 on lipid metabolism is highlighted by the increase of plasma total cholesterol observed in rheumatoid arthritis patients upon tocilizumab therapy (56). Taken together with our study, those findings suggest that IL-6 is an inflammatory cytokine that may exert a Janus role in metabolic diseases, and further studies are, therefore, required to elucidate the complete spectrum of its pathophysiological actions.…”

Tocilizumab in rheumatoid arthritis: efficacy, safety and its place in therapy

“…Multiple logistic regression analysis indicated concurrent hepatic dysfunction and concomitant methotrexate use as risk factors for this, and particular attention should be paid to the monitoring of hepatic function markers (risk of hepatic dysfunction with concurrent hepatic dysfunction: odds ratio 2.546, 95% CI 1.681-3.857; risk of hepatic dysfunction with concomitant methotrexate use: odds ratio 2.174, 95% CI 1.705-2.771). Levels of low-density and high-density lipoprotein cholesterol may rise immediately after TCZ has been administered; however, the atherogenic index remains steady [Kawashiri et al 2011] and it is unknown whether or not rises in cholesterol directly increase the risk of cardiovascular events. Routine cholesterol control should be practiced [Nishimoto et al 2010].…”