Use of biologicals in dermatology – following the agreed path or going off-piste? A brief report

Author byline as per print journal:
Michael Wilcock, MPhil; Andrew Pothecary, MSc

Introduction: Biological medicines are used to treat a range of conditions according to National Institute for Health and Care Excellence (NICE) technology appraisals. The annual drug treatment cost per patient per year varies depending on various factors, including newer or older biological, and availability of a biosimilar. Our biologicals pathway for dermatology (moderate or severe psoriasis) listed less expensive older biologicals (including biosimilars) early on in the treatment choices and more recently approved (and generally more expensive) choices lower down the pathway.
Objective: We aimed to identify which biologicals or selective immunosuppressants were used first line in adult patients with moderate or severe psoriasis, and ascertain if the reasons for use of treatments other than adalimumab were in accordance with the locally agreed pathway.
Methods: Medical records were reviewed for a sample of patients prescribed biologicals during late 2019 and early 2020. We identified patients who had commenced any treatment. Contact was made with lead dermatology nurses if needed.
Results: There were 33 patients commenced on a biological – 17 had newly started biological therapy and 16 had switched from a prior biological therapy to a new therapy. Of the 17 new patients, two commenced apremilast (biological contraindicated), 10 commenced adalimumab, and five commenced other biologicals. Of these five who commenced other biologicals, two were on guselkumab, two on ustekinumab, and one on certolizumab. In all five instances there was a valid reason for not using adalimumab as first choice though this was not always explicit in the multidisciplinary team (MDT) documentation.
Discussion: Though the number of psoriasis patients (17) newly starting a biological medicine was relatively small, it was reassuring that for five of these who commenced a subcutaneous biological other than adalimumab, there was a valid reason for this choice, though not always explicit in the MDT letter, which Dermatology will ensure is clear for future decisions. Hence going ‘off-piste’ was deemed justified.
Conclusion: This very small-scale study found that the local guideline was followed with patients commencing treatments other than biosimilar adalimumab for valid reasons.

 Submitted: 19 May 2021; Revised: 26 August 2021; Accepted: 26 August 2021; Published online first: 8 September 2021

Introduction/Study Objectives

Psoriasis, a common, chronic, non-communicable skin disease, affects at least 100 million individuals worldwide, and has great negative impact on patients’ quality of life [1]. Initial psoriasis treatments include topical and systemic therapies, as well as phototherapy, and are designed to control only symptoms. Clearance of all skin lesions has become a realistic goal as a result of the introduction of a wide variety of biological drugs. The different biological drugs approved for use in moderate to severe psoriasis provide targeted inhibition of immune-mediated pathways involving specific cytokines, such as tumour necrosis factor (TNF) (e.g. etanercept, infliximab, adalimumab, and certolizumab pegol), interleukin (IL)-17 (e.g. secukinumab, ixekizumab, and brodalumab), and IL-23 (e.g. ustekinumab, guselkumab, tildrakizumab, and risankizumab).

This range of options of biologicals and oral treatments for moderate to severe psoriasis can be a challenge for clinicians, patients, and policymakers when deciding how the medicines compare in terms of efficacy and safety. There are a limited number of head-to-head trials even though network meta-analyses have been undertaken [2-5].

Across England and Wales, guidance from the National Institute for Health and Care Excellence (NICE) assesses the clinical and cost effectiveness of health technologies, including pharmaceuticals. The National Health Service (NHS) is legally obliged to fund and resource medicines and treatments recommended by NICE’s technology appraisals (TA). Furthermore, the NHS Constitution, which sets out rights to which patients, public and staff are entitled, and pledges which the NHS is committed to achieve, states that patients have the right to drugs and treatments that have been recommended by NICE for use in the NHS, if their doctor believes they are clinically appropriate [6]. NICE’s guidance on psoriasis describes the various treatment options for psoriasis, identifying the relevant TA [7]. The annual medicine acquisition cost to the NHS for treating a patient with moderate to severe psoriasis can range from approximately £3,000 to £13,000 depending on various factors, including availability of a biosimilar of the biological, e.g. for infliximab, etanercept, adalimumab, and whether there is a patient access scheme associated with the TA. A patient access scheme or commercial arrangement when associated with NICE guidance is a way in which pharmaceutical companies lower the acquisition cost of a medicine to the NHS to improve its cost-effectiveness, so enabling patients to gain access to high-cost medicine treatments. For instance, in the NICE TA for guselkumunab the discussion of the NICE committee focused on the cost comparison with ixekizumab and secukinumab and took into account all confidential patient access schemes, enabling the committee to conclude that the criteria for a positive cost comparison for guselkumunab were met [8]. High-cost medicines are so named as they are expensive prescribed items, representing a disproportionate cost relative to the total NHS cost of the relevant hospital episode in terms of volume and cost.

Within England there have been a number of ongoing strategies to promote the use of biosimilars in hospitals including educational [9], setting of targets for the proportion of patients who are prescribed biosimilar choices of biologicals [10], and monitoring the local adoption of biosimilars by regional teams that facilitate implementation of national policy measures [11].

Our hospital is a 750-bed acute secondary care hospital in the south-west of England. The Dermatology Department developed a biologicals pathway which describes use of oral medicines, e.g. methotrexate or ciclosporin, and ultraviolet light therapy prior to the use of biologicals or selective immunosuppressants, e.g. apremilast, and then defaults to biosimilar adalimumab as first choice injectable treatment, see Flowchart 1.

Flowchart 1 pending to upload

Other biologicals may be chosen depending on various patient considerations. This pathway was approved by the health system-wide prescribing committee (composed of clinicians, pharmacists, and commissioners) in February 2019. Within Dermatology, patients considered for starting or switching biological treatment are discussed at a monthly multi-disciplinary team (MDT) meeting, attended by a hospital pharmacist.

The hospital, in conjunction with the local clinical commissioning group (CCG), utilizes the Blueteq high-cost drug management system. CCGs are statutory regional NHS bodies that are responsible for the planning and commissioning of healthcare services for their local area. Many CCGs in England use this Blueteq web-based system which allows clinicians to complete an online proforma for patients prescribed a high-cost medicine, such as a biological, and receive automatic approval for funding if the patient meets all the relevant criteria which normally reflect the NICE TA guidance. This ensures that clinicians receive the approval to treat immediately. The Blueteq system retains, as an audit trail, the request history, including patient name, drug, indication, criteria for use, date of request, requesting clinician, and whether the request was granted or not. This enables CCGs to monitor the use of expensive treatment, so that only treatments prescribed in line with NICE guidelines are reimbursed to the hospital

We aimed to identify which biologicals or selective immunosuppressants were used first line in adult patients with moderate or severe psoriasis, and ascertain the reasons for use of treatments other than adalimumab.

Methods

This was a retrospective, single site study. An extract was downloaded from the Blueteq system for a five-month period commencing November 2019 for adult patients granted approval to commence treatment for moderate to severe plaque psoriasis. This sample was chosen as a recent time period after allowing for a few months to pass since the guideline was approved in March 2019. Relevant data (patient demographics and treatment details) were imported into Excel by a member of the pharmacy team. The medical records of any patients commenced on treatments other than adalimumab were reviewed, and contact was made with the lead nurse in Dermatology if the records did not provide sufficient explanation for the treatment choice.

Health Research Authority criteria about research and service evaluation were considered. This was a retrospective assessment involving no changes to the service delivered to patients, and we used the NHS Health Research Authority tool (http://www.hradecisiontools.org.uk/research/index.html) which helped confirm that no ethical approval was required for this project. Patient data were used in accordance with local NHS hospital policy.

Results

Over the five-month period, 33 patients (mean age 49 [range 20–82] years, 13 [39%] male) were commenced on one of the medicines of interest, see Table 1. Seventeen (52%) of these patients (mean age 49 [range 23–82] years, 9 [53%] male) were biological-naïve, whilst the remaining 16 were registered on Blueteq as they had switched from a prior biological therapy to a new therapy. Patients switching treatment were excluded as most had commenced their previous medicine prior to the introduction of the pathway.

Table 1 pending to upload

Of the 17 biological-naïve patients, two commenced apremilast (as a biological was contraindicated), 10 commenced adalimumab, and five commenced other biologicals. Of these five, two were initiated on guselkumab, two on ustekinumab and one on certolizumab pegol. There was a documented reason in the medical records for choosing a biological other than adalimumab for two of these five patients and in the other three cases, the lead nurse in Dermatology was able to access other records to clarify the reason for the decision. These are summarized in Table 2.

Table 2 pending to upload

Discussion

This small-scale study found that the local guideline from early 2019 was followed as there were valid reasons for patients commencing treatments other than biosimilar adalimumab. Our agreed guideline is not overly prescriptive and deviation is allowed if the MDT agree that it is appropriate for the patient under discussion. The local guideline mirrors advice from national bodies in choice of certolizumab pegol in pregnancy [12, 13]. Guselkumab as first choice for palmoplantar pustulosis or specific body areas however was not explicitly supported by guidance that has emerged since the local guideline was produced [12, 13]. However, the NICE TA does state that evidence from clinical trials and indirect comparisons shows that guselkumab is more effective than TNF-alpha inhibitors, e.g. adalimumab [8]. The evidence papers supporting this appraisal refer to the main comparison with adalimumab [14] noting that guselkumab showed superior clearance when used to treat regional psoriasis, such as scalp, finger nails, and hand and foot. The absolute differences for regional psoriasis outcomes favoured guselkumab by between 10% to 18%. The NICE TA at that time would not have considered the much lower cost to the NHS of a biosimilar adalimumab, and it is not clear from an incremental cost effectiveness viewpoint if patients with these hard-to-treat psoriatic areas should be treated with the less expensive biosimilar adalimumab first before moving on to guselkumab. Some studies do mention guselkumab as first choice based on small patient numbers [14, 15].

Overly prescriptive guidelines that require drugs to be used in a certain sequence with little scope for deviation may be good at controlling costs but may not be clinically appropriate as they do not allow for clinical judgement to over-ride the guideline where it is needed. If deviation from a guideline is tightly restricted this may increase demands on health services if patient’s needs are not adequately met, e.g. repeat clinic visits, poor mental health, comorbidity. The MDT approach allows for discussion of options with decisions reached by consensus not majority, helping to standardize practice across the specialty as decisions on treatment are no longer made by a single clinician. Involvement of nurses and pharmacist in the MDT allows consideration from different perspectives, and in our context the pharmacist is also involved with the Rheumatology team as well, which is useful when it comes to managing patients with psoriatic arthritis.

We recognize the limitations of a single centre, very small-scale study and that we do not report follow up of patients in relation to any improvement in their psoriasis. These results therefore cannot be generalized to other hospitals and to other indications for these classes of medicines.

A recent meta-analysis found that most biologicals cluster together with respect to short-term efficacy and tolerability, and the authors were unable to identify any single agent as ‘best’ [5]. It is argued that the guideline resulting from this meta-analysis [5] and its linked evidence and decision aid will help the confused clinician make the best choices [16]. We argue however that is it may be questionable if this guideline helps the health authority or commissioner payer as well. Hence, local future work should involve a review of our pathway, requiring the MDT decisions to be more explicit in their documentation, reviewing the initiation of biologicals over a longer time period, and possibly comparing pathways from different hospital Dermatology departments.

Conclusion

In this very small study, the choice of first-line biological for the treatment of moderate or severe psoriasis was in accordance with our local guideline in the majority of patients. Where deviation from the guideline occurred this was justified on clinical grounds, though documentation of these could be improved. These preliminary results from a very small sample size suggest the need for a larger study of the effectiveness of the guidelines over a longer period.

Funding sources

There were no funding sources.

Competing interest: None.

Provenance and peer review: Not commissioned; externally peer reviewed.

Authors

Michael Wilcock, MPhil
Pharmacy Department

Andrew Pothecary, MSc
Rheumatology Department

Royal Cornwall Hospitals NHS Trust, Truro, Cornwall TR1 3lJ, UK

Author for correspondence: Michael Wilcock, MPhil, Pharmacy Department, Royal Cornwall Hospitals NHS Trust, Truro, Cornwall TR1 3lJ, UK

References pending to upload

Disclosure of Conflict of Interest Statement is available upon request.

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