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Methofill® (methotrexate) SelfDose—results from a real-world patient survey

Jiten Modha, Highly Specialist Pharmacist for Gastroenterology and Rheumatology, Department of Pharmacy, Evelina London Children’s Hospital, St Thomas’s Hospital

 

Key points

  • Methofill® SelfDose device has an ergonomic design and is different from traditional injection devices or pre-filled syringes that are currently available on the market
  • Methofill® SelfDose is easy to grip and may particularly support patients with dexterity issues
  • The majority of patients are confident injecting Methofill® SelfDose at home
  • The majority of patients were satisfied with Methofill® SelfDose device
  • The study was not a direct head-to-head comparison of the different methotrexate devices
  • A larger, multicentre study across both primary and secondary care is needed for more decisive conclusions.

Introduction

Autoimmune diseases are characterised by an abnormal immune response whereby the body produces antibodies that attack and potentially damage its own tissues or organs. This heightened immune response can affect any organ system in the body and accounts for more than 80 immune- mediated diseases. Some common autoimmune diseases include rheumatoid arthritis, Crohn’s disease, and psoriasis.1

It is hypothesised that several factors could increase the risk for an autoimmune disease. These include: gender, age, ethnicity, family history, and exposure to environmental agents. 2

Rheumatoid arthritis 

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease that can cause cartilage and bone damage as well as physical disability.3 According to the National Rheumatoid Arthritis Society, about 1% of the population in the UK has RA—more than 400,000 people.4 It is two to three times more prevalent in women than in men, with an average age of onset between 40–60 years of age. However, people can be diagnosed as young as 14, when it is termed early onset RA.4 The heterogenicity of this chronic disease means that there are various subtypes of RA, so drug treatment is tailored to help control symptoms and improve quality of life (QoL).

Symptoms vary in degree of severity ranging from mild to severe. Most commonly patients may experience pain, swelling, redness, stiffness, and fatigue.4 Severe and progressive symptoms tend to be associated more with chronic RA. In such cases, patients may experience chronic fatigue, loss of appetite, low grade fever, loss in the range of motion of a particular joint, and joint deformity. RA is a systemic disease that can also affect the whole body, including the heart, lungs and eyes.5

Symptom control is key to improving QoL of patients. Patients with RA can live with constant pain that limits their day-to-day activities.6 Maintaining a healthy lifestyle with regular exercise and eating healthily can help and may also help to alleviate secondary symptoms, such as fatigue and mental health issues, while overall improving the patient’s QoL.7

Crohn’s disease

Crohn’s disease and ulcerative colitis account for the two main types of inflammatory bowel disease. Crohn’s disease is characterised by the transmural inflammation of any part of the gastrointestinal tract, that is, from the mouth to the anus. Most commonly the ileum and the colon are affected.8 In the intestines the inflammation may also be associated with ‘skip’ regions—sections of normal gut between inflamed areas. Crohn’s disease affects one in every 650 people in the UK and can occur at any age but is more prevalent between the ages of 10 and 40.8

The severity of symptoms varies from patient to patient and depends where the active disease is.8 Patients may have asymptomatic phases; however, these can be followed with periods of intense symptoms and inflammation, classified as ‘flares’. Inflammatory symptoms include: persistent diarrhoea, rectal bleeding, constipation, and abdominal cramps and pain.8

As with RA, QoL depends on the severity of symptoms and the frequency of flares. Pharmacological management and diet control can help control symptoms, reduce the frequency of flares, and improve periods of wellbeing. However, in certain instances the disease state is so active that despite pharmacological treatment, diet control, and surgical intervention, patients may experience constant symptoms that result in them having to adapt their day-to-day life.8

Psoriasis

Psoriasis is a chronic scaling disease of the skin that can affect any part of the body and is associated with red raised patches known as plaques. It is often found on the elbows, knees, and scalp but can be widespread.9 One in 50 people is affected and the condition is evenly distributed between men and women.10 Most commonly patients may experience itching with little pain; however, the condition can also affect the nails and/or joints. The severity of this autoimmune disease varies from mild to severe; more severe cases are associated with anxiety and depression and an increased risk of cardiovascular disease.10

Psoriasis has a significant negative impact on patients’ health-related QoL. In a survey by the National Psoriasis Foundation of people with psoriasis, almost 75% believed that psoriasis had a moderate to large negative impact on their QoL, with alterations in their daily activities.11 Patients with psoriasis often experience difficulties like maladaptive coping responses, problems with body image, self-esteem, self-concept, alongside feelings of stigma, shame, and embarrassment about their appearance.12

Treatment

The treatment of autoimmune diseases is based on reducing the heightened immune response and so reducing any associated inflammation and pain. Treatment depends on the severity and type of disease. Dietary control and environmental factors may also help to alleviate symptoms. 

Broadly, symptomatic control treatment usually involves the use of anti-inflammatory drugs. Steroids may be used to further reduce inflammation or for periods when patients experience ‘flares’. Disease-modifying anti-rheumatic drugs (DMARDs) such as methotrexate have an immunosuppressive effect and form the basis for most treatment pathways. Immunomodulatory drugs, such as biologic therapies, tend to form the final stage in drug therapy. Biologics target specific inflammatory mediators to stop the immune response further up in the inflammatory cascade and thus help to reduce inflammation. As these drugs are biologically manufactured, they are more costly and so are found further along treatment pathways. 

Methotrexate

Methotrexate, a DMARD, is a folic acid antagonist that belongs to the class of cytotoxic agents known as antimetabolites. It acts by the competitive inhibition of the enzyme dihydrofolate reductase and thus inhibits DNA synthesis.13 It is not yet clear whether the efficacy of methotrexate in the management of psoriasis, psoriatic arthritis, chronic polyarthritis, and Crohn’s disease, is due to an anti-inflammatory or to an immunosuppressive effect and to what extent a methotrexate-induced increase in extracellular adenosine concentration at inflamed sites contributes to these effects.13 Most patients will experience a response to treatment within approximately 4–8 weeks.13

Methotrexate is available in a variety of pharmaceutical forms. These include tablets, oral solution, pre-filled syringes and pre-filled syringe for injection, for example Methofill® SelfDose.

Methofill® SelfDose

Methofill® SelfDose is a pre-filled injector device containing methotrexate for self-injecting. It is available in a variety of dosages with the packaging being colour-coded to aid dose differentiation. The ergonomic handle design aids patients to inject using this single-use device on a weekly basis.

A Methofill® SelfDose patient survey was commissioned by Accord in partnership with Day Lewis plc Pharmacies between April 2019 and May 2020.14 Patients were identified by assessing the patient records for repeat prescriptions of Methofill® SelfDose. Those who were initiating or filling their first prescription for Methofill® were excluded. A total of 63 patients were identified, all of whom were adults aged ≥ 18 years with active rheumatoid arthritis, psoriasis vulgaris, psoriatic arthritis, or Crohn’s disease.14

The survey questionnaire captured:14

  • subject demographics: 
    • age and gender
  • experience self-injecting methotrexate:
    • number of years injecting methotrexate
    • other methotrexate self-injecting devices used before Methofill® SelfDose
    • fear or concerns about self-injecting methotrexate
  • perceptions of Methofill® SelfDose: 
    • ease of use
    • preference of Methofill® SelfDose versus other methotrexate self-injection devices used in the past 
  • levels of confidence and satisfaction with Methofill® SelfDose
    • confidence to inject Methofill® SelfDose at home
    • overall satisfaction with Methofill® SelfDose device.

Of the 63 responses, three questionnaires were excluded from the final analysis as these patients highlighted that they did not self-inject. Thus, a total of 60 patients were analysed as part of the final cohort.14

Demographically, of the 60 patients analysed 61.7% (n=37) were ≥ 60 years of age and 33.3% (n=20) were between the ages of 36 and 59 years, and 5% (n=3) were between the ages of 18 and 35. 61.4% (n=35) patients were female and 38.6% (n=22) were male (n=3 respondent chose not to answer this question).14

The survey highlighted that the majority of patients had previous experience of self-injecting methotrexate. Although this is not a necessity, it instils confidence and allows patients to take ownership in the management of their disease. The results showed that 55% (n=33) of patients had between 2–5 years’ experience, and 28.3% (n=17) had over 5 years’ experience. Three patients were excluded as they did not self-inject.14

Before they switched to the Methofill® SelfDose device, 54.2% (n=32) patients had used Metoject® Pen injector. Twenty-two percent (n=13) had previously used pre-filled syringes, and 3.4% (n=2) had used Nordimet® Pen injector.14

One of the key positives from the study was that the majority of patients did not have negative perceptions of self-injecting methotrexate. The question focused on concerns and fears and the results showed that 80.7% (n=46) had none, 8.8% (n=5) had a lack of confidence, 3.5% (n=2) needle phobia, and 8.8% (n=5) fear of pain. Patients could select more than one response within the question; two patients selected two responses. Three patients were excluded as they did not complete the question.14

Another key finding was that Methofill® SelfDose as a device was easy to grip. Although the sample size was small (total n=57, three patients answered not applicable), 31.6% (n=18) strongly agreed and 43.9% (n=25) agreed with the statement, 10.5% (n=6) were neutral in their response (see Figure 1).14

Figure 1

N=57; no missing data. Three N/A responses corresponded to 3 respondents who answered ‘I have a carer or HCP who administers injection.’

HCP=healthcare professional

Figure 1: Methofill® SelfDose device is easy to grip when giving your injection.10

Methofill® SelfDose has an ergonomic handle design to aid with self-administration. Again, although there was a limited cohort of patients who answered this question, analysis showed that 33.3% (n=19) strongly agreed with the statement Methofill® SelfDose was easy to use. 42.1% (n=24) agreed and 10.5% (n=6) were neutral in their response. A total of 14.1% (n=8) either disagreed or strongly disagreed with the statement (See Figure 2).14

Figure 2

N=57; no missing data. Three N/A responses corresponded to 3 respondents who answered ‘I have a carer or HCP who administers injection.’

HCP=healthcare professional

Figure 2: I find Methofill® SelfDose easy to use.10

Another key finding from the study was that the majority of patients were confident in self-injecting Methofill® SelfDose at home, further highlighting its ease of use. Of the 57 patients who answered this question, 43.9% (n=25) and 45.6% (n=26) strongly agreed and agreed, respectively, that ‘I am confident to self-inject Methofill® SelfDose at home’. A very small proportion of this cohort disagreed with this statement: 3.5% (n=2), and strongly disagreed 1.8% (n=1).14

The final question also showed some promising results. Patients were asked overall to quantify how satisfied they were with the Methofill® SelfDose device for administering their methotrexate injection. They were asked to rank this on a scale of 1–10 with 1 being not at all satisfied and 10 being very satisfied. Of the 60 patients who answered this question, overall 73.3% (n=44) of patients had a degree of satisfaction scoring 6 and above. Only 26.7% (n=16) had a degree of dissatisfaction scoring 5 and below (see Figure 3). From a patient perspective within this cohort, Methofill® SelfDose has demonstrated that:14

  • it does not have any specific or additional concerns for patients versus other self-injecting devices
  • the device is easy to grip, and this may particularly assist patients who have poor dexterity attributed to their autoimmune disease
  • it is easy to use
  • patients are confident in using the device to self-inject at home
  • patients are overall satisfied with the device.

Figure 3

N=60; no missing data. 

Figure 3: Overall, how satisfied are you with the Methofill® SelfDose device for administering methotrexate injections?.10

Study limitations

At the time when the study was commissioned, Methofill® SelfDose had just been introduced to the market, so establishing a suitable cohort of patients proved difficult. Ideally a larger cohort of patients was required to justify any conclusive findings and instil confidence in the findings. Contributing factors possibly include the fact that patients were recruited from only one community pharmacy chain—Day Lewis plc—and within this it is difficult to quantify if there was any geographical bias. The study does not specify the diversity of the patients or whether they were from one part of the UK.

However, even with the limited number of patients recruited the results are positive and encouraging. As with all the methotrexate subcutaneous preparations, it will have its own positives and negatives; however patient choice and preference plays a key part in overall decision making. 

Summary

This small cohort survey has shown some promising outcomes for the use of Methofill® SelfDose. Sixty-two percent of patients were over the age of 60, with 83.3% of patients self-injecting methotrexate for over 2 years. 54.2% of patients had previously used Metoject® Pen Injector with 80.7% of patients having no concerns or fears about self-injecting methotrexate. 75.5% agreed that Methofill® SelfDose was easy to grip and 75.4% agreed it was easy to use. In addition, 89.5% of patients, either strongly agreed/agreed that they were confident in injecting this device at home, while 73.3% were satisfied overall with the device.

Conflicts of interest

The author has received an honorarium to write this article; he also received consultancy fees from other pharmaceutical companies, which may include Accord-UK Ltd, for activities other than writing this article.

References

  1. Medicine Plus. Autoimmune diseases. (accessed April 2021).
  2. Pollard K. Environment, autoantibodies, and autoimmunity. Front Immunol 2015; doi10.3389/fimmu.2015.00060/full 
  3. Smolen J, Aletaha D, McInnes I. Rheumatoid arthritis. Lancet 2016; 388 (10055): 2023–2038.
  4. National Rheumatoid Arthritis Society. What is RA? (accessed April 2021).
  5. NICE. Rheumatoid arthritis in adults: management. NICE Guideline 100. NICE, 2018.Available at:
  6. Ezerioha M. Life with RA: what will my quality of life be like?  (accessed April 2021).
  7. Arthritis Action. Rheumatoid arthritis.  (accessed April 2021).
  8. Crohn’s & Colitis UK. Crohn’s disease. (accessed April 2021).
  9. Primary Care Dermatology Society. Psoriasis: an overview and chronic plaque psoriasis. Last updated 2019. (accessed April 2021).
  10. British Skin Foundation. Psoriasis. (accessed April 2021).
  11. Bhosle M, Kulkarni A, Feldman S et al. Quality of life in patients with psoriasis. Health Qual Life Outcomes 2006; 4: 35. 
  12. Fortune D, Richards H, Griffiths C. Psychologic factors in psoriasis: consequences, mechanisms, and interventions. Dermatol Clin 2005; 23 (4): 681–694. 
  13. Accord Healthcare Limited. Methofill 12.5 mg solution for injection in pre-filled injector. Summary of product characteristics.
  14. Accord-UK Ltd. Methofill (methotrexate) Self Inject patient survey report. June 2020.

Case study—prescribing of Methofill® SelfDose in a rural GP practice

Caroline Pond, Clinical Pharmacist and Operation Director, Medacy Ltd, Bedale.

Overview

This case study examines the outcomes in a primary care setting of several patients who were either initiated on or switched to Methofill® SelfDose device in general practice. The patients were either fully supported in the use of the new device by GP practice staff or managed the initiation of the Methofill® SelfDose device independently.

 

Background

Working as a pharmacist in general practice can be challenging when it comes to managing patients’ needs in a consistent manner. Working with a team in a dispensing practice brings further challenges. Ideally, a pharmacist in a retail or hospital setting would check the  knowledge of a patient when dispensing a new medication device from a prescription; however, when the dispensing is being carried out by dispensers this does not always happen, because the  knowledge about the medicine is primarily with the prescribing clinicians rather than at dispensary level. Unless there are protocols in place, many initial supplies slip through the net and are handed to the patient without formal counselling.

While there could be an argument that these supplies will be few and far between, this is not always true. Medication switches in primary or secondary care can be triggered with various outcomes in mind, e.g. to save the NHS money, to increase profit (or reduce loss) in a dispensing practice, or because of medication shortages related to a particular brand. 

Initiation of injectable methotrexate usually occurs in secondary care with full support from the clinic’s staff on the specific device used in that institution; however, device selection at the point of dispensing is only directive if the prescription is written for a branded product. Generic prescribing, widely encouraged within the NHS, can lead to variation of device supply if more than one device meets the generic specifications on the prescription.

This article discusses the events and outcomes surrounding the prescribing and supply of injectable methotrexate in a rural dispensing GP practice in England.

Case study

Situation: a dispensary team find their current purchasing brand of injectable methotrexate out of stock with the usual wholesaler.

Decision: they order an alternative available injectable methotrexate device in order to give the patients continuity of supply. 

Outcomes: while we would like to claim this was done in an organised and measured manner, in actuality the dispensary staff in this GP practice simply ordered the Methofill® SelfDose alternative to the current methotrexate strength and supplied the items to the patients. They consulted the British National Formulary (BNF) and checked on the clinical system, and as the prescription was written generically and the products are completely interchangeable as far as the molecule supplied, the team did not have particular concerns. They had even gone so far as to check the injection was the same with the GP on duty. It was only when I received a call from one of the affected patients who wanted to check that they understood how to use the device correctly that I realised something was wrong.

At the time, a total of five patients were supplied with the Methofill® SelfDose device without any instruction or communication regarding the change. All patients were long standing users of injectable methotrexate and all had previously been started on an alternative device by the rheumatology team at the local hospital. In each case a shared care protocol and dosage instructions were in place. 

Once the situation regarding the change of device supplied had been drawn to my attention, the other patients who had been supplied with Methofill® SelfDose were rapidly identified and contacted as a matter of urgency.

The findings from the telephone consultations with the patients concerned were interesting:

  • two patients had not yet looked at their prescription items and it was possible to ask them to book an appointment with one of the healthcare assistants (HCA) in the practice to carry out the first injection with the device; this required the HCA undergoing some training herself which was carried out by myself using the Methofill® SelfDose training online 
  • the following two patients had quite simply worked it out for themselves—one 80-year old patient had watched the Methofill® SelfDose video on the Methofill® website and followed the instructions; the other used the product insert to follow the step-by-step guide and had successfully injected themselves that same morning
  • the final patient was having difficulties understanding how the device worked, but was happy to talk through the process over the phone and when contacted again a couple of weeks later was happy to report that she had successfully injected herself as instructed.

Each of these five patients continued to use the device successfully and, when asked, had no issues with the device; three reported preferring the ‘needleless’ appearance of the Methofill® SelfDose device over the previously prescribed device.

In line with the Methofill® SmPC, patients must be educated to use the proper injection technique and the first injection of methotrexate should be performed under direct medical supervision; however, as highlighted in this case study, this does not always happen in practice.

Learning points: since this not very professional approach to changing methotrexate device in our practice, we now have a robust process for switching or initiating patients on the Methofill® SelfDose device; the HCA reports that most patients are perfectly able to manage the change with minimal intervention—a brief discussion and pointing them in the direction of the device resources is usually enough.

We currently have more than 10 patients receiving prescriptions for methotrexate injections and all bar one receive Methofill® SelfDose.

Observations

The Methofill® SelfDose device is usually well received by patients in primary care, and patients can be easily transitioned or initiated with simple instructions and access to further advice if required. The video presentation is very well received by patients as this allows them to watch the instructions as many times as they like before using their device for the first time.

One further observation is that the prescribing team should be aware of the need for a cytotoxic sharps container with a larger aperture than the one usually supplied in general practice. We have had numerous phone calls in the initial stages of prescribing Methofill® SelfDose from patients who were concerned about getting the devices into their existing bins.

Summary

Running a consultation with patients when dispensing a new medication or when switching their current device to a different one is important to check the patients’ knowledge and understanding. Even interchangeable devices (e.g. different methotrexate injection devices) can have different operating procedures, and it is important the patient is trained to confidently apply them.

Conflicts of interest

The author has received an honorarium to write this article; she also received consultancy fees from other pharmaceutical companies, which may include Accord-UK Ltd, for activities other than writing this article.

Adverse events should be reported.
Reporting forms and information can be found at www.mhra.gov.uk/yellowcard
Adverse events should also be reported to Accord-UK LTD on 01271 385257

This supplement has been commissioned and funded by Accord-UK Ltd and developed in partnership with Guidelines in Practice. Accord-UK Ltd suggested the topic and authors, and carried out full medical approval on all materials to ensure compliance with regulations. The authors have been paid an honorarium. The views and opinions of the authors are not necessarily those of Accord-UK Ltd, or of Guidelines in Practice, its publisher, advisers, or advertisers. No part of this publication may be reproduced in any form without the permission of the publisher. 

UK-03037

Date of preparation: May 2021