Abstract
BackgroundIn pharmacological conditioning associations are formed between the effects of medication and contextual factors related to the medication. Pharmacological conditioning with placebo medication can result in comparable treatment effects and reduced side effects compared to regular treatment in various clinical populations, and may be applied to achieve enhanced drug effects. In the current study protocol, pharmacological conditioning is applied to achieve enhanced treatment effects in patients with recent-onset rheumatoid arthritis (RA). The results from this study broaden the knowledge on the potential of pharmacological conditioning and provide a potential innovative treatment option to optimize long-term pharmacological treatment effectiveness for patients with inflammatory conditions, such as recent-onset RA.MethodsA multicenter, randomized controlled clinical trial is conducted in patients with recent-onset RA. Participants start on standardized pharmacological treatment for 16 weeks, which consists of methotrexate (MTX) 15 mg/week and a tapered schedule of prednisone 60 mg or 30 mg. After 4 months, participants in clinical remission (based on the rheumatologist’s opinion and a targeted score below 1.6 on a 44-joint disease activity score (DAS44)) are randomized to 1 of 2 groups: (1) the control group (C), which continues with a standardized treatment schedule of MTX 15 mg/week or (2) the pharmacological conditioning group (PC), which receives an MTX treatment schedule in alternating high and low dosages. In the case of persistent clinical remission after 8 months, treatment is tapered and discontinued linearly in the C group and variably in the PC group. Both groups receive the same cumulative amount of MTX during each period. Logistic regression analysis is used to compare the proportion of participants with drug-free clinical remission after 12 months between the C group and the PC group. Secondary outcome measures include clinical functioning, laboratory assessments, and self-reported measures after each 4-month period up to 18 months after study start.DiscussionThe results from this study broaden the knowledge on the potential of pharmacological conditioning and provide a potential innovative treatment option to optimize long-term pharmacological treatment effectiveness in patients with inflammatory conditions, such as recent-onset RA.Trial registrationNetherlands Trial Register, NL5652. Registered on 3 March 2016.
Highlights
In pharmacological conditioning associations are formed between the effects of medication and contextual factors related to the medication
An example is pharmacological conditioning, which is a form of both classical conditioning, whereby associations are formed between the medication effect and contextual factors related to the medication, and instrumental learning, whereby conscious expectations of the drug effects will lead to symptom reduction [1, 3,4,5,6,7]
Pharmacological conditioning is increasingly accepted as a possible promising therapeutic strategy to optimize treatment outcome, as clinical studies indicate its effectiveness in various clinical populations [8,9,10,11,12,13]
Summary
In pharmacological conditioning associations are formed between the effects of medication and contextual factors related to the medication. In the current study protocol, pharmacological conditioning is applied to achieve enhanced treatment effects in patients with recent-onset rheumatoid arthritis (RA). The repeated coupling of the contextual factors with the intake of an active drug, which is accompanied by an unconditioned response (the drug effect), leads to a learned response, the conditioned response (CR), which is similar to the unconditioned response. After forming these associations, the CS in itself (e.g., a placebo tablet looking similar to the active medication) can elicit the CR. The formation of associations between contextual factors and the medicinal effect is a key factor in this process and occurs mainly automatically after the active medication had its effect on disease symptoms [3, 15, 16]
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