Estimated impact for the NHS

Other treatments

A wide range of adjuvant treatments are available for people with Parkinson's disease who are experiencing end-of-dose motor fluctuations on levodopa alone, including other catechol-O-methyl transferase (COMT) inhibitors (entacapone and tolcapone). Entacapone is licensed for adjuvant therapy to levodopa/DOPA decarboxylase inhibitor (DDCI) in people with Parkinson's disease and end-of-dose motor fluctuations which cannot be stabilised on these combinations. Tolcapone is licensed for adjuvant therapy to levodopa/DDCI in people with Parkinson's disease and motor fluctuations, when other COMT inhibitors are not tolerated or when they have failed. Tolcapone is prescribed under specialist supervision only and needs frequent monitoring of liver function. Entacapone is commonly prescribed as a combination product, levodopa/carbidopa/entacapone (Prescription cost analysis, England 2015).

Alternative adjuvant options include dopamine agonists (for example, pramipexole, ropinirole and rotigotine) and monoamine oxidase‑B (MAO‑B) inhibitors (for example rasagiline, selegiline and safinamide).

Costs of other treatments

See table 3 for the costs of other COMT inhibitors.

Table 3 Costs of other treatments

Medicine/treatment

Usual dose

30‑day cost, excluding VAT a

Entacapone 200 mg tabletsb

200 mg taken with each levodopa/DDCI dose up to 10 times a dayf

£50.30b, c

Tolcapone 100 mg tablets (Tasmar)

100 to 200 mg 3 times a day as adjunct to levodopad

£85.68 to £171.36e

Abbreviation: DDCI, DOPA decarboxylase inhibitor.

a Based on maximum daily dose, taken from the relevant summary of product characteristics (SPC). These directions do not represent the full range that can be used and they do not imply therapeutic equivalence.

b Entacapone is also available as a combination preparation with different strengths of levodopa and carbidopa.

c Costs taken from Drug Tariff, February 2017 (excluding VAT).

d The SPC for tolcapone states that the dose should only be increased to 200 mg 3 times a day in exceptional circumstances, when the anticipated incremental clinical benefit justifies the increased risk of hepatic reactions.

e Costs taken from MIMS, February 2017 (excluding VAT).

f Specialists who commented on this evidence summary suggested that for most people, entacapone is taken between 4 and 7 times a day.

Current or estimated usage

The manufacturer estimates the number of people prescribed opicapone over the next 3 years will be 747 (2017), 1,748 (2018) and 2,982 (2019).

Likely place in therapy

Entacapone is the most prescribed COMT inhibitor as adjunctive therapy to levodopa and may be taken up to 10 times daily with each levodopa dose to manage end-of-dose motor fluctuations in Parkinson's disease. The use of tolcapone is limited because of the increased risk of hepatotoxicity and can only be prescribed and supervised by physicians experienced in the management of advanced Parkinson's disease (SPC: tolcapone). Opicapone is the third COMT inhibitor licensed in the UK as adjunctive therapy to levodopa in people with Parkinson's disease who are experiencing end-of-dose motor fluctuations. Opicapone is taken once a day, which enables a simplified regimen compared with entacapone, although combination preparations of entacapone/levodopa/DDCI are available and are frequently prescribed.

Specialists who reviewed this evidence summary highlighted that a combination product of entacapone may be difficult for some people who are on differing levodopa doses at different times of the day. Some people taking complicated dosing regimens may find it easier to add in a single tablet like opicapone and keep their familiar levodopa doses over the day. In addition, using a once-daily opicapone enables flexible dosing of levodopa without altering opicapone dose, unlike when using entacapone. Specialists who commented on this evidence summary suggested that opicapone may be an option to consider when entacapone is not tolerated or is inadequate at controlling symptoms. The majority of the participants in the study were taking additional medicines for Parkinson's disease such as dopamine agonists, monoamine oxidase inhibitors, anticholinergics and amantadine. Therefore, there are limited data on the use of opicapone as a first choice adjunctive therapy to levodopa.

Opicapone 50 mg showed efficacy in the primary outcome measure and also in most secondary outcomes including clinician and patient global assessment of change (see clinical effectiveness). The magnitude of effect of opicapone 50 mg with a reduced off time of 60.8 minutes and an increase in on time without troublesome dyskinesia of 62.6 minutes compared with placebo was considered clinically relevant and moderate (European public assessment report [EPAR]: opicapone). The duration of time in the on state with troublesome dyskinesia did not change. Opicapone 50 mg was shown to be non-inferior to entacapone 200 mg for improving motor fluctuations and indicated a greater reduced off time compared with entacapone.

The EPAR for opicapone states that the daily dose of 50 mg has proven to be consistently efficacious. BIPARK I demonstrated efficacy of opicapone 50 mg in up to 15 weeks only. Reduction in off time was sustained for 1 year with opicapone 25 mg to 50 mg in an open-label study (Lees et al. 2016; BIPARK II). The incidence of serious treatment-emergent adverse events with opicapone did not differ from that in the placebo or entacapone groups (Ferreira et al. 2016). The most common adverse events reported with opicapone were dyskinesia, constipation, insomnia and dry mouth. The EPAR for opicapone states that dyskinesias were reported in more than 10% of participants receiving opicapone in which case it may be necessary to reduce the levodopa dose within the first days to first weeks after starting opicapone to prevent severe dyskinesias.

In addition to effectiveness, safety and patient factors, local decision-makers will need to take cost into account when considering the likely place in therapy of opicapone. Opicapone is more expensive than entacapone, which is the most commonly prescribed COMT inhibitor: 30‑day treatment costs (excluding VAT) for: opicapone 50 mg is £93.90 (MIMS, February 2017); entacapone based on maximum dose is £50.30 (Drug Tariff, February 2017); and tolcapone based on 100 mg dose is £85.68 (MIMS, February 2017).

The NICE guideline on Parkinson's disease makes recommendations on the place in therapy of adjuvant treatments, including COMT inhibitors (see introduction and current guidance). The choice of treatment will depend on the person's clinical and lifestyle characteristics, and their preferences, after an informed discussion about the benefits and risks of treatment.