Journal of Clinical Nursing 2002; 11: 256–263
`
`A study of parenteral use of methotrexate
`in rheumatic conditions
`
`VALERIEVALERIE ARTHURARTHUR R G N , M P h i l
`
`
`Rheumatology Nurse Specialist, Rheumatology Department, University Hospital Birmingham
`NHS Trust, Selly Oak Hospital, Birmingham, UK
`
`RONALDRONALD JUBBJUBB M D , F R C P
`
`
`Consultant Rheumatologist, Rheumatology Department, University Hospital Birmingham NHS
`Trust, Selly Oak Hospital, Birmingham, UK
`
`DAWNDAWN HOMERHOMER R G N
`
`
`Rheumatology Nurse Specialist, Rheumatology Department, University Hospital Birmingham
`NHS Trust, Selly Oak Hospital, Birmingham, UK
`
`Accepted for publication 20 July 2001
`
`Summary
`
`• This paper reports the findings of a small pragmatic study to compare the
`safety and efficacy of methotrexate administered by intramuscular and subcu-
`taneous injection, and to teach patients to self-administer methotrexate by the
`subcutaneous route.
`
`• Eight patients with rheumatic conditions, already receiving a stable weekly
`dose of methotrexate by intramuscular injection, were entered into this 13-week
`study.
`
`• Serum levels of methotrexate were measured on six consecutive occasions:
`three whilst patients received intramuscular methotrexate and then three after
`switching to the subcutaneous route.
`
`• Patients were taught to self-administer their methotrexate subcutaneously and
`were then discharged to perform this task at home.
`
`• Levels of disease activity and psychological scores were measured at the start
`and end of the study. Satisfaction with self-administration and teaching of
`injection techniques were assessed at 13 weeks.
`
`• Serum methotrexate levels were not significantly affected by the route of
`administration. All patients were able to perform self-injection safely and seven
`out of eight preferred self-administration at home.
`
`• This small study demonstrates that there is no difference in the safety and
`efficacy of methotrexate given by either parenteral route. Patients were able to
`
`Correspondence to: Valerie Arthur, Rheumatology Department, Ward
`E1, University Hospital, Birmingham NHS Trust, Selly Oak Hospital,
`Raddlebarn Road, Birmingham B29 6JD
`(e-mail: valerierichards@dial.pipex.com).
`
`256
`
`(cid:211) 2002 Blackwell Science Ltd
`
`Page 1 of 8
`
`KOIOS Exhibit 1023
`
`

`
`Issues in caring for people with long-term conditions
`
`Parenteral use of methotrexate
`
`257
`
`administer safely methotrexate subcutaneously. Self-administration reduced
`hospital visits, was more convenient
`for patients and improved patient
`satisfaction.
`
`Keywords:
`injections, methotrexate, patient education, patient satisfaction,
`rheumatology, self-administration.
`
`Introduction
`
`Methotrexate (MTX), one of several disease-modifying
`anti-rheumatic drugs (DMARDs), is used to treat rheu-
`matic diseases such as rheumatoid arthritis and psoriatic
`arthritis. It may be given orally or parenterally, although it is
`not licensed in the UK for the latter route of administration.
`Patients are usually prescribed oral MTX. However, where
`this is ineffective or poorly tolerated due to nausea and
`gastrointestinal upset (Consumers’ Association, 1995), it
`may be given as a weekly intramuscular (IM) injection.
`Methotrexate may be better tolerated and more effective in
`this form (Brooks et al., 1990). It is not normal practice in
`rheumatology for MTX to be prescribed by subcutaneous
`(SC) injection except for paediatric patients (Wallace,
`1998). Concerns about the safety of using parenteral MTX
`centre on its cytotoxic properties and the dangers associated
`with handling and spillage. In the UK professional
`guidelines exist for its safe administration and disposal
`(RCN, 1989; Royal Marsden Hospital NHS Trust, 1996a).
`For some years a number of patients with a variety of
`rheumatic conditions attended rheumatology nurse-led
`clinics at a district general hospital on a weekly basis to
`receive IM injections of MTX. They had previously tried
`oral MTX but it proved either to be ineffective or poorly
`tolerated by this route, resulting in a change of administra-
`tion to weekly IM injections. Their continued care in nurse-
`led clinics rather than in primary care was for several reasons:
`the general practitioner was unwilling for them to receive a
`cytotoxic drug in the health centre; district nurses were
`unwilling to administer the injections in patients’ homes; or
`the consultant rheumatologists preferred hospital supervi-
`sion by nurse specialists because of disease complexities. The
`question was asked whether some patients could be safely
`discharged to self-administer their own injections at home,
`with improved convenience for themselves and a reduction
`in hospital visits. In order to do this a switch from the IM
`route of administration to the SC route was considered.
`
`Literature review
`
`A literature review revealed that few studies have been
`undertaken to look at the safety and efficacy of the
`
`(cid:211) 2002 Blackwell Science Ltd, Journal of Clinical Nursing, 11, 256–263
`
`parenteral routes of injectable MTX. A study by Brooks
`et al. (1990) looked at the pharmacokinetics of adminis-
`tration by the two parenteral routes. This small study was
`of five patients with rheumatoid arthritis (RA) already
`taking MTX, but by which route was not disclosed. Each
`patient was randomly assigned to be given two injections
`either of IM MTX or SC MTX, at the same dose as their
`current MTX therapy, and a week apart. Serum MTX
`levels were measured at intervals ranging from time zero
`to 8 h post-injection. Peak concentration values varied
`between the routes of administration and between patients
`but was not shown to be statistically significant. No
`patients complained of any problems relating to the SC
`injection and most found it less painful than the IM route.
`The authors mention the advantages of self-administration
`of SC MTX at home and support its use.
`A brief report by Zackheim (1992) describes how 10
`dermatology patients were given SC MTX injections over
`a period of between 3 to 17 weeks. Six had previously
`been receiving IM MTX injections. It was found that SC
`injections were well
`tolerated,
`less painful, easier to
`administer and clinical response appeared to be similar to
`IM MTX. Zackheim notes that SC injections can be self-
`administered, which is an advantage to patients who would
`otherwise need to make weekly hospital visits for MTX
`administration.
`A study by Jundt et al. (1993) compared the bioavail-
`ability of low dose MTX given by oral solution, oral
`tablet, SC route and IM route. Baseline serum concen-
`trations of MTX were determined for 12 patients with RA
`who were already taking MTX weekly. Over three
`consecutive weekends the subjects were randomized to
`receive MTX either by oral solution, oral tablet or IM
`injection. In an extension to the study six subjects
`returned to receive their MTX as an SC injection. Serum
`MTX concentration was measured at intervals from a
`quarter of an hour post-injection to 24 h post-injection.
`The results
`indicated that
`there was no significant
`difference between the bioavailability of MTX with either
`the SC or the IM routes of injection, and that these two
`routes of injection are interchangeable. The biovailability
`of the tablets was found to be lower than the injection and
`the authors suggest that adjustments should be made to
`
`Page 2 of 8
`
`KOIOS Exhibit 1023
`
`

`
`258
`
`V. Arthur et al.
`
`dosages when changing patients from oral to parenteral
`administration.
`A report by Wallace (1998) that looked at the use of
`MTX in childhood rheumatic diseases, notes that children
`are prescribed higher doses of MTX than adults. The SC
`route is preferred as absorption is better, few gastrointes-
`tinal side-effects occur, and considerable savings occur
`when parents (and/or teenagers) are taught
`to self-
`administer SC MTX at home, compared with the cost
`of tablets.
`This was reflected in a retrospective study of SC MTX
`vs. oral MTX in RA and juvenile rheumatoid arthritis
`(JRA) by Ostrov et al. (1998) that demonstrated that SC
`MTX was more cost-effective than oral MTX. Fifty-two
`patients, 16 with JRA and 36 with RA had received oral
`MTX followed by SC MTX for at least 3 months each.
`The results showed that 73% of patients were switched
`from oral to SC injection due to lack of efficacy. Efficacy
`improved in 65% after the switch and 79% were able to
`self-administer SC MTX. Moreover, the cost of switching
`the route of administration to SC MTX saved $676 000
`annually for a population of 1000 RA and JRA patients.
`Another retrospective study by Arthur et al. (1999),
`from the University of British Columbia, describes the
`safety, efficacy and practicality of self-administration of
`MTX or gold by the IM route. Forty patients, with RA
`and psoriatic arthritis (PSA), were selected to self-
`administer their injections. Twenty were receiving gold,
`17 were receiving MTX and three were receiving both
`drugs. They or a partner were taught IM self-injection
`techniques and were assessed at baseline and every
`3 months thereafter. Compliance was measured by self-
`report, regular monitoring of adherence, drug supply
`requirements and attendance at clinic appointments.
`Patient satisfaction with self-injection was assessed by
`questionnaire. The authors conclude that self- injection is
`convenient for patients in terms of time-saving and costs.
`Clinic visits were reduced from a mean of every 2 weeks to
`every 12th week, indicating substantial savings for the
`health care system. Some problems with non-compliance
`were identified relating to monitoring or injection sched-
`ules. The authors highlight the importance of patient
`education to prevent serious adverse outcomes.
`In conclusion, the studies by Brooks et al. (1990) and
`Jundt et al. (1993) involved only single parenteral doses of
`MTX, small sample sizes and did not look at efficacy or
`patient satisfaction. The study by Zackheim (1992) used a
`small group of dermatology patients. Therefore, no
`conclusive evidence can be drawn from these three
`et al.
`studies. Brooks
`(1990)
`state that
`there is no
`significant difference between the two parenteral routes
`
`of administration. Jundt et al. (1993) concur with this
`opinion and state that the two routes of administration are
`interchangeable. Ostrov et al.
`(1998)
`found that
`the
`efficacy of MTX was increased after switching from the
`oral to the parenteral route. The general opinion appears
`to be that self-administration at home is practical com-
`pared with clinic attendance. The advantages noted by
`Brooks et al. (1990), Zackheim (1992) and Arthur et al.
`(1999) relate to time-saving and cost. The cost savings
`arising from a switch to parenteral MTX from the oral
`route are also noted by Wallace (1998) and Ostrov et al.
`(1998).
`The paucity of studies into the efficacy and safety of
`parenteral MTX is noted by Arthur et al. (1999) and
`reinforces the suggestion by Wallace (1998) that appro-
`priate investigations could optimize the dosage, frequency
`of administration and route of delivery of this treatment.
`
`Design of the study
`
`This was a comparative, descriptive study with both
`qualitative and quantitative aspects. There were two aims
`to the study: to determine whether SC MTX is as safe and
`effective as IM MTX and whether patients could safely
`self-inject SC MTX at home. The objectives of the study
`were to compare blood levels of MTX whilst patients
`received MTX by each route, to assess the impact of
`changing from IM to SC on disease activity, to teach
`patients to safely administer their own injections by the
`SC route and to gauge patient satisfaction with self-
`administration of SC MTX.
`
`Sample selection
`
`Patients were enrolled from those already receiving IM
`MTX for a variety of rheumatic disorders, and who had
`been on a stable dose for a least 1 month. The study had
`been approved by the regional health service ethics
`committee. All participants received written information
`and written consent was obtained.
`
`Research Instruments
`
`An open-ended questionnaire format was used to gain
`qualitative data about symptoms of
`increased disease
`activity from this heterogeneous group. The measures of
`disease activity used were tender and swollen joint counts,
`duration of early morning stiffness (EMS), pain and
`fatigue visual analogue scales (VAS), erythrocyte sedi-
`mentation rate (ESR), C reactive protein (CRP) and in the
`case of one subject creatinine phosphokinase (CPK).
`
`(cid:211) 2002 Blackwell Science Ltd, Journal of Clinical Nursing, 11, 256–263
`
`Page 3 of 8
`
`KOIOS Exhibit 1023
`
`

`
`Issues in caring for people with long-term conditions
`
`Parenteral use of methotrexate
`
`259
`
`Patients were asked to complete both the Stanford Health
`Assessment Questionnaire (HAQ) (Fries et al., 1980) and
`the Hospital Anxiety and Depression Scale (HAD) (Snaith
`& Taylor, 1985). At the end of the study additional
`questionnaires were used to determine patient satisfaction
`and any problems relating to the self-administration of SC
`MTX.
`
`Data collection
`
`Data were collected in five stages.
`
`
`
`STAGE 1STAGE 1
`
`Participants were requested to write down what happened
`to them when their arthritis was better and also when it
`was worse. These qualitative data were used to ensure that
`measurements of disease activity were specific for each
`participant within this small heterogeneous population,
`and that
`the activity of symptoms relevant
`to their
`particular disease could be measured.
`
`
`
`STAGE 2 (3 WEEKS)STAGE 2 (3 WEEKS)
`
`Patients were assessed by one of the nurse specialists (VA)
`for baseline parameters of disease activity as described
`above. Further data recorded at baseline included age,
`gender, rheumatic condition, disease duration and length
`of time on IM MTX. For 3 consecutive weeks metho-
`trexate was administered by IM injection by the clinical
`nurse specialists and blood was taken, 1 h after each
`injection, for measurement of MTX levels.
`
`
`
`STAGE 3 (3 WEEKS)STAGE 3 (3 WEEKS)
`
`The route of MTX administration was switched to SC
`injection, which was administered as specified in the
`Manual of Clinical Nursing Procedures (Royal Marsden
`Hospital NHS Trust, 1996b). For 3 consecutive weeks the
`injections were given by the clinical nurse specialists and
`on each occasion blood was taken, 1 h post-injection, for
`measurement of MTX levels.
`At each visit during this stage participants were taught,
`by the two nurse specialists (VA and DH),
`to self-
`administer SC injections. Comprehensible written infor-
`mation sheets, based on a question and answer format,
`about the injection technique, disposal of used syringes
`and how to deal with any spillage of MTX, were given to
`each participant. These assisted in the teaching process
`and provided participants with a reminder when they
`undertook the procedure at home.
`
`(cid:211) 2002 Blackwell Science Ltd, Journal of Clinical Nursing, 11, 256–263
`
`Before the study commenced, discussions had taken
`place with the hospital pharmacist to ensure that MTX
`injections could be provided in 2-ml Luer lock syringes. It
`had been observed that sometimes the needle can be
`pulled off the end of the syringe when the needle guard is
`removed and also that patients with poor hand function
`could more easily grasp a wider syringe then the pen-type
`syringe that is more commonly used for SC injections. It
`was anticipated that 2-ml Luer lock syringes would avoid
`any problems. Syringes with needles already attached
`could not be provided as the sterility of the drug could not
`be guaranteed by the hospital pharmacy.
`
`
`
`STAGE 4 (3 WEEKS)STAGE 4 (3 WEEKS)
`
`Participants self-administered their MTX subcutaneously
`under the supervision of the nurse specialists at the
`hospital for 3 consecutive weeks. This was to ensure that
`the procedure was carried out in a sterile and safe manner.
`They were assessed regarding their ability to safely self-
`administer the injections and also the safe storage of their
`injections at home. These needed to be stored in a
`refrigerator and care taken that they were not accessible to
`children. Three pre-filled syringes in a lockable box,
`needles, alcohol swabs and a sharps disposal box were
`provided and participants were discharged for a month.
`They were advised to use the rheumatology telephone
`helpline number should they encounter any problems with
`self-administration between hospital visits.
`
`
`
`STAGE 5 (4 WEEKS)STAGE 5 (4 WEEKS)
`
`Participants self-administered their MTX by the SC route
`at home for 3 consecutive weeks. They then returned to
`the nurse-led clinics to collect further injections, for the
`clinical nurse specialist to review their self-administration
`technique, and for safety monitoring of
`their MTX
`therapy. Monitoring for safety was done at weeks 1, 4, 9
`and 13. Disease activity was measured at this hospital visit
`for comparison against the baseline parameters.
`
`Results
`
`
`
`STAGE 1STAGE 1
`
`The qualitative data gained from the open-ended ques-
`tionnaire reflected the views of the individual participants.
`The use of an open-ended question asking about ‘What
`happens when your arthritis is better and when it is
`worse?’ permitted participants to express their experience
`freely. The measurement of health status in rheumatic
`
`Page 4 of 8
`
`KOIOS Exhibit 1023
`
`

`
`260
`
`V. Arthur et al.
`
`conditions, such as RA, can be difficult as symptoms vary
`considerably between patients. It is important therefore to
`understand the patient’s perspective (Ryan, 1998).
`Content analysis of the qualitative data obtained from
`Stage 1 revealed that pain, fatigue, joint swelling, stiffness,
`loss of
`function,
`immobility and depression were all
`factors related to increased disease activity for this group.
`These symptoms are commonly exhibited by patients with
`rheumatic disease and it was decided therefore to adopt
`the disease activity and outcome measures recommended
`by the OMERACT Committee (1993), namely the number
`of tender and swollen joints, visual analogue scale for pain,
`and functional status using the HAQ (Fries et al., 1980).
`Physician and patient global assessment, acute phase
`reactants and radiological damage were excluded as not
`being useful for this study. Other measures used in
`addition were the duration of early morning stiffness
`(EMS), fatigue, anxiety and depression using the HAD
`questionnaire (Snaith & Taylor, 1985).
`
`
`
`STAGE 2STAGE 2
`
`Demographic data
`
`Thirteen patients were invited to participate in the study.
`Five were receiving their IM MTX in primary care
`
`settings and eight were receiving their treatment at the
`nurse-led hospital clinics. The five from primary care were
`contacted by telephone, given an explanation of the study,
`and invited to participate. All declined, preferring to
`remain in primary care for the following reasons: one
`participant preferred to have the injection at home given
`by her husband, two were given it by the nurse as it was
`‘too far to come to the hospital’, two others said that ‘their
`hands were too bad to give the injection themselves’.
`Of the eight participants who entered the study, two
`were male and six were female. Disease characteristics,
`disease duration, age range and length of time on MTX
`are shown in Table 1.
`
`Serum levels of MTX
`
`Analysis of weekly serum levels of MTX were undertaken
`by the biochemistry department using routine assays. As
`shown in Table 2, these varied within individuals each
`week and also between the two routes of administration,
`even although blood was taken strictly at 1 hour post-
`injection. There was no significant difference in blood
`serum levels between IM and SC MTX injections. Brooks
`et al. (1990) found slightly different MTX serum levels in
`their study of IM MTX vs. SC MTX and they list the
`possible factors that may influence this as being: change of
`
`Participant
`No.
`
`Gender
`
`Age
`(yr)
`
`Disease
`
`Disease
`duration
`(months)
`
`Duration
`IM/MTX
`(months)
`
`Dose
`(mg)
`
`Stable
`dose
`(months)
`
`01
`M
`55
`PSA
`48
`15
`7.5
`2
`02
`F
`52
`WG
`30
`13
`22.5
`16
`03
`F
`36
`RA
`72
`6
`15
`1
`04
`F
`49
`PMS
`72
`5
`7.5
`5
`05
`F
`58
`RA
`364
`11
`12.5
`4
`06
`F
`50
`RA
`132
`19
`15
`11
`07
`F
`38
`RA
`62
`5
`10
`2
`08
`M
`55
`PSA
`312
`75
`25
`48
`RA(cid:136) rheumatoid arthritis; WG(cid:136) Wegener’s granulomatosis; PSA(cid:136) psoriatic arthritis; PMS(cid:136)
`polymyositis.
`
`Participant
`No.
`
`01
`02
`03
`04
`05
`06
`07
`08
`
`Week 1 Week 2 Week 3 Mean IM Week 4 Week 5 Week 6 Mean SC
`
`0.5
`1.1
`0.01
`0.35
`0.85
`0.66
`0.75
`1.65
`
`0.55
`1.5
`0.54
`0.6
`0.83
`0.58
`0.81
`1.8
`
`0.67
`0.97
`0.47
`0.29
`0.69
`0.92
`0.55
`1.8
`
`0.57
`1.19
`0.34
`0.41
`0.79
`0.72
`0.7
`1.05
`
`0.44
`1.59
`0.55
`0.51
`0.76
`1.05
`0.67
`1.5
`
`0.44
`1.35
`0.48
`0.75
`0.48
`0.99
`0.78
`1.32
`
`0.38
`1.75
`0.59
`0.27
`0.64
`0.81
`0.84
`0.88
`
`0.42
`1.56
`0.54
`0.51
`0.62
`0.95
`0.76
`1.07
`
`Table 1 Demographic data
`
`Table 2 Weekly and mean serum
`methotrexate levels (mmol L)1)
`
`(cid:211) 2002 Blackwell Science Ltd, Journal of Clinical Nursing, 11, 256–263
`
`Page 5 of 8
`
`KOIOS Exhibit 1023
`
`

`
`Issues in caring for people with long-term conditions
`
`Parenteral use of methotrexate
`
`261
`
`drug administration sites, changes in injection technique
`and differences in blood circulation at different times. The
`first two factors apply to this study, with the changes from
`the thigh as the injection site for IM MTX to the
`abdomen for SC injection.
`
`Disease activity
`
`The results of pre- and post-measures of disease activity
`relating to fatigue, pain, early morning stiffness (EMS)
`and counts for tender and swollen joints were inconclu-
`sive. There was no overall definite increase or decrease in
`these parameters, either in particular participants or at the
`beginning and end of
`the study. Four participants
`reported more fatigue, four reported more pain, one
`reported more stiffness, two had a few more painful joints
`and one had several more swollen joints. Conversely, four
`reported less fatigue, four reported less pain and seven
`experienced the same amount of stiffness.
`Levels of disease activity in the blood (ESR, CRP and
`CPK) showed little difference beyond the variations which
`would occur within the normal fluctuations in disease
`activity (Huskisson & Dudley Hart, 1987).
`
`Physical and psychological status
`
`The Health Assessment Questionnaire (HAQ), to assess
`daily living activities, and the Hospital Anxiety and
`Depression Scale (HAD), to assess psychological status,
`were completed by participants at the beginning and end
`of the study. The results showed little difference in either
`activities of daily living or anxiety and depression.
`
`Patient satisfaction
`
`An important aspect of the study was satisfaction with the
`teaching for self-administration and support from the
`nurses. Participants were asked to complete questionnaires
`
`Table 3 Satisfaction chart
`
`Participant
`No.
`
`How taught by
`the nurses?
`
`Giving the injection
`to yourself?
`
`which used attitudinal scales as demonstrated in Table 3.
`All participants, except one (participant no. 5), felt very
`satisfied with how they were taught to give the injections,
`and all were very satisfied with the support from the
`rheumatology nurses.
`Qualitative data were also gathered from the additional
`questionnaires about self-administration. Participants felt
`‘OK’ or had ‘no problems’, one admitted to ‘feeling
`nervous’, one was ‘unsure at first’ and one felt ‘confident’.
`One person wrote that the subcutaneous injections were
`‘painless and easy’.
`
`
`
`PROBLEMS RELATING TO THE SELF-ADMINISTRATIONPROBLEMS RELATING TO THE SELF-ADMINISTRATION
`
`OFOF MTXMTX
`
`the study participants were asked to
`the end of
`At
`complete a further questionnaire designed to discover any
`problems with self-administration. Participant 5 reported
`difficulties giving the injection and putting the needle on
`to the syringe, stating ‘It is difficult because of poor hand
`function’. Participant 2 ‘Found it difficult to get the cap
`off the needle’. Another participant (No. 7) reported a
`‘clean needle-stick injury’. Although not reported by the
`participant as a problem,
`it
`should be noted that
`participant 1 also incurred a clean needle-stick injury
`when administering his first SC MTX injection under the
`supervision of the nurse specialist. Clean needle-stick
`injuries, i.e. stabbing oneself before giving the injection,
`appear to relate to difficulties with removing the guard
`from the needle, and were noted at the start of the study.
`Skin irritation at the injection site was reported by three
`participants. Participant 2 related this to some itching,
`which was later attributed to a reaction to the plaster
`applied after the injection. Participant 5 noticed slight,
`local tenderness to touch but reported that this was less
`than with IM MTX. Another participant (No. 7) reported
`one incident of
`irritation and some bleeding at
`the
`injection site but no recurrence of this.
`
`01
`02
`03
`04
`05
`06
`07
`08
`
`Very satisfied
`Very satisfied
`Very satisfied
`Very satisfied
`Satisfied
`Very satisfied
`Very satisfied
`Very satisfied
`
`OK
`Unsure at first but becoming familiar
`I feel OK
`OK
`I felt confident
`No problems
`Nervous
`Fine, no problems
`
`(cid:211) 2002 Blackwell Science Ltd, Journal of Clinical Nursing, 11, 256–263
`
`Support from
`nurses
`
`Very satisfied
`Very satisfied
`Very satisfied
`Very satisfied
`Very satisfied
`Very satisfied
`Very satisfied
`Very satisfied
`
`Anything you feel
`we should know
`
`None
`None
`None
`None
`None
`None
`None
`Painless and easy
`
`Page 6 of 8
`
`KOIOS Exhibit 1023
`
`

`
`262
`
`V. Arthur et al.
`
`
`
`PATIENT PREFERENCEPATIENT PREFERENCE
`
`Participants were asked whether they would prefer to
`give their injections at home or come to the hospital, and
`were also asked to write down why this was. As shown in
`Table 4, most preferred to give their injection at home
`and all had reasons for their preference. One preferred to
`visit the hospital but described herself as ‘accident prone’
`and, it should be noted, had a self-inflicted needle-stick
`injury on her first self-administration at home. It is
`interesting to note that two participants ‘missed’ attend-
`ing for their regular hospital visits. This may relate to
`the psychological support that is so important for many
`patients with a chronic disease such as arthritis (Ryan,
`1998).
`
`
`
`OUTCOMESOUTCOMES
`
`the study was that all
`The immediate outcome of
`participants safely administered their injections at home,
`resulting in a reduction in visits to the nurse-led clinics.
`The reduction in clinic visits has implications for
`patients and health service provision. As regards patients,
`these are difficult to calculate but relate to financial aspects
`such as work hours lost and the cost of transport. It is also
`difficult to measure the cost of inconvenience to patients
`in terms of time spent travelling to and from hospital and
`time spent in the clinic waiting to be seen. One implication
`for health service provision is that new referrals are seen
`sooner in the nurse-led clinics, thereby reducing the
`waiting list
`for these clinics. This means that
`these
`patients can be started more quickly on new therapies,
`thus helping to prevent ‘flares’ of their arthritis with the
`consequent necessary input from members of the rheu-
`matology team. As a result of these implications, this
`therapy has been more widely prescribed within the study
`
`Participant
`No.
`
`Home or
`hospital?
`
`Reason given
`
`hospital and offers patients another therapeutic option
`which they might otherwise have been denied.
`
`Limitations of the study
`
`The main limitation of the study was the small number of
`participants, making it impossible to generalize the results.
`Another limitation was that it is impossible to determine
`fully the costs that may be reduced in terms of time and
`inconvenience for patients and permitting the nurse
`specialists to be more profitably employed in educating
`and treating newly diagnosed patients. In a recent study in
`Canada by Arthur et al. (1999), the cost-savings of self-
`administration of injectable gold and MTX were related to
`weekly travel, parking and time for patients, whilst for the
`health care system they were related to costs of nursing
`time or physician visits.
`It should also be noted that the study was carried out by
`the nurses who were also giving the injections, teaching
`self-injection techniques and supporting the participants.
`This highlights another limitation to the study in that
`there could have been some bias towards the investigators
`which may have influenced the responses to the satisfac-
`tion questionnaire.
`
`Recommendations
`
`It is recommended that patients currently receiving MTX
`by the IM route should be switched to the SC route and
`assessed with a view to self-administering their therapy at
`home.
`In the future parenteral MTX should be prescribed by
`the SC route instead of the IM route.
`Patients who are able should self-administer their
`injections at home. Routine monitoring for drug side-
`effects should continue, as should assessment of injection
`
`Table 4 Preference for injections at
`home or at hospital
`
`01
`02
`
`03
`
`04
`05
`06
`
`07
`08
`
`Home
`Home
`
`Home
`
`Home
`Home
`Home
`
`Hospital
`Home
`
`Less time from work
`I feel I have my life back although I miss the feedback from
`the nurses
`Because it is much easier than to keep coming here. Because when
`I come sometimes I don’t get home for the children from
`school but now I am there for them
`I feel relaxed at home
`I can do it in my own time and I’m more relaxed
`It saves coming to the hospital every week, as I only have to
`come every four weeks now for supplies and blood tests!
`Because I am accident prone!
`A matter of convenience. I obviously miss the regular visits.
`
`(cid:211) 2002 Blackwell Science Ltd, Journal of Clinical Nursing, 11, 256–263
`
`Page 7 of 8
`
`KOIOS Exhibit 1023
`
`

`
`Issues in caring for people with long-term conditions
`
`Parenteral use of methotrexate
`
`263
`
`technique to ensure that this has not been compromised
`by any deterioration in hand function.
`A carer should be taught this task for patients who are
`unable to self-administer.
`
`Conclusion
`
`This paper has reported on a small study designed to
`compare the safety and efficacy of methotrexate admin-
`istered by two different parenteral routes. Whilst it is not
`possible to generalize the results, it is possible to state
`that no difference was demonstrated between the routes
`of administration in terms of efficacy.
`It was also
`demonstrated that
`selected patients can safely self-
`administer SC MTX at home,
`thereby reducing the
`number of visits to the nurse-led clinics and freeing up
`time for the nurse specialists to see more referrals to
`their clinics. As the United Kingdom government seeks
`to shift the focus of care from hospital services to the
`community (Department of Health, 1997)
`the self-
`administration of drugs can be seen as integral to that
`initiative.
`
`References
`
`Arthur A.B., Klinkhoff A.V. & Teufel A. (1999) Safety of self-
`injection of gold and methotrexate. The Journal of Rheumatology
`26(2), 302–305.
`Brooks P.J., Spruill W.J., Parish R.C. & Birchmore D.A. (1990)
`Pharmacokinetics of methotrexate administered by intramuscular
`and subcutaneous injections in patients with rheumatoid arthritis.
`Arthritis and Rheumatism 33(1), 91–95.
`Consumers’ Association (1995) Independent review for doctors and
`pharmacists. Methotrexate for rheumatoid arthritis. Drugs and
`Therapeutics Bulletin 33(3), 17–19.
`
`Department of Health (1997) The New NHS – Modern and
`Dependable. Department of Health, London.
`Fries J.F., Spitz P.W., Kraines R.G. & Holman H.R. (1980)
`Measurement of patient out-come in arthritis. Arthritis and
`Rheumatism 23, 137–45.
`Huskisson E.C. & Dudley Hart F. (1987) Joint Disease: All the
`Arthropathies. Wright, Bristol.
`Jundt J.W., Browne B.A., Fiocco G.P., Dean Steele A. & Mock D.
`(1993) A comparison of low dose methotrexate biovaliability. Oral
`solution, oral tablet, subcutaneous and intramuscular dosing.
`Journal of Rheumatology 20, 1845–1849.
`Ostrov B., Robbins L., Ferriss J.A., Newman E., Maclary S., Ayoub
`W., Harrington T. & Perruquet J. (1998) Improved tolerance and
`cost-effectiveness of sub-cutaneous versus oral methotrexate in
`rheumatoid arthritis and juvenile rheumatoid arthritis (Abstract
`257). Arthritis & Rheumatism 41(9) (Suppl.), S75.
`RCN (1989) Safe Practice with Cytotoxics. Royal College of Nursing
`Oncology Society, London.
`Royal Marsden Hospital NHS Trust (1996a) Cytotoxic drugs:
`handling and administration. In Manual of Clinical Nursing
`Procedures, 4th edn (eds J. Murcott & C. Bailey). Blackwell
`Science, Oxford, pp. 191–203.
`Royal Marsden Hospital NHS Trust (1996b) Drug administration.
`In Manual of Clinical Nursing Procedures, 4th edn (eds J. Murcott
`& C. Bailey). Blackwell Science, Oxford, pp. 241–242.
`Ryan S. (1998) The essence of rheumatology nursing. In Rheuma-
`tology Nursing. A Creative Approach (ed. J. Hill). Churchill
`Livingstone, Edinburgh, pp. 3–17.
`Snaith R.P. & Taylor C.M. (1985) Rating scales for depression and
`anxiety: a current perspective. British Journal of Clinical Phar-
`macy 19, 175–205.
`OMERACT Committee (1993) Proceedings of the OMERACT
`Conference