Cost-Effectiveness Modelling of Sequential Biologic Strategies for the Treatment of Moderate to Severe Rheumatoid Arthritis in Finland

Abstract: Objective: The main objective was to compare the cost-effectiveness of therapeutic options in moderate or severe rheumatoid arthritis (RA) when a clinical response to a first TNF-blocker, either etanercept (ETA), adalimumab (ADA), or infliximab (INF), is insufficient. Methods: Effectiveness criteria were defined as remission (RS), low disease activity (LDAS), and moderate to high disease activity (MHDAS). Cost-effectiveness was derived as cost per day in RS and in LDAS using simulation modelling to assess six sequential biologic strategies over 2 years. Each sequential treatment strategy was composed of three biologic agents and included a first anti-TNF agent, ETA, ADA or INF, followed by either abatacept (ABA) or rituximab (RTX) as a second therapeutic option in case of an insufficient response, followed by another anti-TNF agent in case of further insufficient response. Results: Over two years and taking into account biologic costs, the following estimated mean costs per day in RS and LDAS were respectively of �829 and �428 for the biologic sequence composed of ADA-ABA-ETA, �1292 and �516 for the sequence ADA-RTX-ETA, �829 and �429 for the sequence ETA-ABA-ADA, �1292 and �517 for the sequence ETA-RTX-ADA, �840 and �434 for the sequence INF-ABA-ETA, and �1309 and �523 for the sequence INF-RTX-ETA. Conclusion: The treatment sequences including ABA as the second biologic option appear more cost-effective than those including RTX in a patients with moderate to severe RA and an insufficient response to a first anti-TNF agent. Keywords: Cost-effectiveness, rheumatoid arthritis, biologics, modelling

Effect of acute nicotine administration on striatal dopamine output and metabolism in rats kept at different ambient temperatures

1. The effect of ambient temperature on the nicotine-induced (0.3, 0.5 or 0.8 mg kg(−1) s.c.) changes of the striatal concentrations of dopamine (DA) and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) was studied in freely-moving rats by in vivo microdialysis. 2. At the ambient temperature of 30–33°C, but not at 20–23°C, nicotine doses of 0.5 (P<0.01) and 0.8 mg kg(−1) (P<0.05) significantly increased the extracellular DA concentration. The nicotine doses of 0.5 and 0.8 mg kg(−1) increased the DA metabolite levels similarly at both ambient temperatures studied (P⩽0.0001), but the dose of 0.3 mg kg(−1) only at 30–33°C (DOPAC: P<0.05; HVA: P<0.01). 3. At 30–33°C, dihydro-β-erythroidine (DHβE 2.8 mg kg(−1) i.p.) blocked the nicotine-induced (0.5 or 0.8 mg kg(−1)) increases of extracellular DA concentration but only tended to antagonize the increases of DA metabolites. Mecamylamine (5.0 mg kg(−1) i.p.) blocked the increase of DA output induced by 0.5 mg kg(−1) but not that induced by 0.8 mg kg(−1) of nicotine and fully prevented the nicotine-induced elevations of DOPAC and HVA. 4. Elevation of ambient temperature did not affect the cerebral concentration of nicotine or the nicotine-induced elevation of serum corticosteroids. Also, the rectal temperatures of rats given nicotine at either ambient temperature did not significantly change. 5. Our results show that the nicotine-induced output of striatal DA is enhanced at high ambient temperature. Further, our findings suggest that the nicotinic cholinoceptors mediating the effects of nicotine on striatal DA release are different from those mediating nicotine's effects on DA metabolism

Biological basis of tobacco addiction: Implications for smoking-cessation treatment

Tobacco use became common all over the world after discovery of Americas. Tobacco, a plant carries in its leaves an alkaloid called nicotine, which is responsible not only for several pathophysiological changes in the body but also develops tolerance to its own action with repeated use. Studies suggest that the alpha-4 beta-2 nicotine acetylcholine receptor subtype is the main receptor that mediates nicotine dependence. Nicotine acts on these receptors to facilitate neurotransmitter release (dopamine and others), producing pleasure and mood modulation. Repeated exposure to nicotine develops neuroadaptation of the receptors, resulting in tolerance to many of the effects of nicotine. Withdrawal symptoms appear on stoppage of tobacco use, which are characterized by irritability, anxiety, increased eating, dysphoria, and hedonic dysregulation, among others. Smoking is also reinforced by conditioning. Pharmacotherapies for smoking cessation should reduce withdrawal symptoms and block the reinforcing effects of nicotine obtained from smoking without causing excessive adverse effects