3. Monitoring patients with moderate to severe psoriasis

Patients with moderate to severe psoriasis are usually managed in secondary care with treatments including phototherapy, methotrexate, ciclosporin, acitretin or TNF inhibitors. Clinicians in primary care may provide repeat prescriptions for these treatments. There needs to be a clear understanding between the dermatologist and general practitioner regarding the responsibility for monitoring patients and requesting blood tests; adverse effects of these medicines can be serious and potentially fatal.

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This is the third article in a series of three on psoriasis. An overview of treatment of chronic plaque psoriasis is available in the first article: Chronic plaque psoriasis: an overview of treatment in primary care . Guidance on selecting topical treatments and tailoring treatment to the affected body area is available in the second article: Choosing a topical treatment for patients with chronic plaque psoriasis.

 

Patients with moderate to severe psoriasis are usually managed in secondary care with the following treatments:

  • Phototherapy: suitable for most patients if topical treatments are not sufficient
  • Methotrexate: the preferred oral treatment for patients with chronic plaque psoriasis
  • Ciclosporin: typically used after trialling methotrexate
  • Acitretin: used if methotrexate and ciclosporin are inappropriate or unsuccessful
  • TNF inhibitors: initiated if other treatments are unsuccessful

Clinicians in primary care may provide repeat prescriptions for these treatments. There needs to be a clear understanding between the dermatologist and general practitioner regarding the responsibility for monitoring patients and requesting blood tests; adverse effects of these medicines can be serious and potentially fatal.

Phototherapy is used for patients with moderate to severe chronic plaque psoriasis who have not responded sufficiently to topical treatments.1 It is most effective for thin plaques on the trunk and limbs.

Narrow band UV-B (NB-UVB) is the preferred form of phototherapy, which involves multiple exposures over six to twelve weeks, that are initially a minute or less and extended over subsequent sessions.2, 3 Other forms of phototherapy, such as psoralen with UV-A exposure (PUVA), are no longer preferred treatments for chronic plaque psoriasis but may be used in select patients.

Tanning beds or sun exposure cannot be used as substitutes for phototherapy. They are less effective in the treatment of psoriasis and have a much wider range of wavelengths than NB-UVB phototherapy with a higher risk of skin damage.4, 5

Patients should not apply topical products prior to phototherapy sessions

Patients are advised not to apply topical products such as salicylic acid or sunscreen prior to phototherapy sessions, as they can interact with UV-B treatment. Calcipotriol, if used, should be applied after rather than before treatment, as it is inactivated by UV light.5

One-third of patients have adverse effects from phototherapy, but specific monitoring in primary care is generally not needed

Adverse effects of NB-UVB phototherapy include erythema, pruritus, burning, stinging and occasionally blistering of the skin.6 Advise patients to report burning or pain following a phototherapy session; the phototherapy team will adjust the dose for future sessions. Painful erythema can be treated with emollients, non-steroidal anti-inflammatory medicines, and a few applications of a mild potency topical corticosteroid.

Treatment with NB-UVB may contribute to the development of wrinkles or telangiectasias.6 Encourage patients to be sun smart to mitigate this risk. Photosensitising medicines such as doxycycline should be prescribed with caution or avoided while the patient is undergoing phototherapy. Evidence suggests NB-UVB treatment is not associated with an increased risk of skin cancer, although guidelines recommend increased monitoring if patients have multiple courses.1, 5 Patients with recurrent cold sores may experience a flare following phototherapy.6

A list of commonly prescribed medicines which are associated with photosensitivity reactions is available at: www.dermnetnz.org/topics/drug-induced-photosensitivity

Continued treatment with topical corticosteroids or calcipotriol may be necessary for plaques that are resistant to phototherapy, or at sites which are difficult to treat, such as the scalp.7

Low-dose methotrexate, a mild immunosuppressant with anti-inflammatory properties, is the preferred oral treatment for patients with moderate to severe plaque psoriasis, typically prescribed at doses of 15–30 mg weekly, taken as one dose per week.7, 8 It is usually initiated by a dermatologist with general practitioners providing follow-up prescriptions, which must have specialist endorsement, for full subsidy.

Monitoring recommendations

Patients taking methotrexate require close monitoring (Table 1) as treatment can cause serious and potentially fatal adverse effects including hepatotoxicity, bone marrow suppression, gastrointestinal bleeding and perforation and haemorrhagic enteritis.9, 10 Blood samples should be taken at least five days after the last dose of methotrexate.

Monitoring of HbA1c and lipid levels is recommended. Evidence shows the risk of hepatotoxicity during methotrexate treatment is increased in patients with obesity, diabetes, or liver conditions such as non-alcoholic steatohepatitis or non-alcoholic fatty liver disease.8

Dermatologists may also request that patients have procollagen type 3 (procollagen 3 N-telopeptide) measured, which is a serum marker of hepatic fibrosis.11 Patients with results and risk factors suggestive of liver disease may require referral for liver elastography to detect liver fibrosis, if available. Pulmonary toxicity is less common in patients with psoriasis taking low-dose methotrexate than in patients with rheumatoid arthritis and specific monitoring of lung function is not required; however, inform patients of potential symptoms, such as dry cough, which could indicate pulmonary toxicity.8, 12 Bone marrow suppression is rare during low-dose methotrexate treatment; when it does occur, this is often associated with prescribing or dispensing errors, reduced renal function or medicines interactions.11 Other adverse effects of methotrexate include fatigue, nausea and headaches; less commonly, mouth ulcers; and rarely, hair loss.13

Table 1. Monitoring for complications during methotrexate treatment.8 §

Pre-treatment Weeks after initiating methotrexate† Thereafter†
2 weeks 4 weeks Every 3 months Every 6 months
Full blood count Tick Tick Tick Tick  
Liver function tests* Tick Tick
(Once in the first 3 months of treatment)
Creatinine and electrolytes** Tick
Lipids and HbA1c Tick Tick
(Every 6 to 12 months)
Pregnancy test Tick

* If transaminase levels are persistently elevated, i.e. over three times the upper limit of normal, consider stopping methotrexate; contact the patient’s dermatologist to discuss

** Approximately 85% of methotrexate is excreted through the kidneys; dose reductions or withdrawal may be required if renal function is reduced10, 12

† Blood samples should be taken at least five days after the last dose of methotrexate

§ Local DHB guidance may vary

Safe prescribing of repeat methotrexate prescriptions

Cases of serious toxicity, including deaths, have occurred when methotrexate has been taken daily instead of weekly, often due to prescribing or dispensing errors.

Key points for safe prescribing include:8, 9, 14

  • Prescribe methotrexate as a specific weekly dose, rather than “as directed”
  • Prescribe 5 mg folic acid, once per week, to be taken at least two days after methotrexate. Methotrexate and folic acid tablets are both yellow.
  • Write days of administration out in full on prescriptions
  • Prescribe one strength of tablet at a time, where possible. If both 10 mg and 2.5 mg tablets are prescribed, point out to patients the differences in tablets, especially if doses change.
  • Warn patients to report symptoms that could indicate:
    • Bone marrow suppression, e.g. fever, sore throat, mouth ulcers
    • Hepatotoxicity, e.g. jaundice, abdominal pain
    • Pulmonary toxicity, e.g. dry cough, dyspnoea
  • Methotrexate interacts with many medicines which can result in increased toxicity and serious adverse effects. For example, serious bone marrow suppression can occur due to interaction with folate antagonists, particularly trimethoprim or co-trimoxazole (trimethoprim + sulfamethoxazole).8 Check for drug interactions using the NZF interactions checker: www.nzf.org.nz/nzf_1
  • Immunisation with live vaccines during treatment should be avoided
  • Methotrexate can cause birth deformities and is contraindicated during pregnancy and lactation.15,16 Whether use in males poses a risk is controversial, however, guidelines and manufacturers advise that both males and females should use appropriate contraception during, and for at least three months following, treatment.10, 11
  • Advise patients to limit alcohol intake to no more than one to two standard drinks once or twice a week10
  • Ensure that patients receive clear instructions in written form. A patient information sheet is available from: www.saferx.co.nz/methotrexate-patient-guide.pdf

Discuss with the patient’s dermatologist if their symptoms fail to improve: methotrexate can be titrated according to clinical response, at recommended increments of 2.5–5 mg per week.10 It may take up to four weeks for a response after increasing doses.17

For further information on adverse effects associated with methotrexate use, see: www.bpac.org.nz/BPJ/2014/October/safer-prescribing.aspx

For most patients with chronic plaque psoriasis ciclosporin is a second-line oral treatment, after methotrexate.7 Ciclosporin can be prescribed by any medical practitioner but is likely to be initiated in secondary care by a dermatologist. For the treatment of chronic plaque psoriasis it is typically taken in short courses of two to four months in doses of 2.5–5 mg per kg per day.7, 10

Monitoring for nephrotoxicity or hypertension

Ciclosporin can cause nephrotoxicity and hypertension and frequent monitoring is recommended, particularly during the first months of use (Table 2). Older patients or those with obesity or diabetes are at an increased risk of nephrotoxicity.18

Common adverse effects

Adverse effects from ciclosporin use include headache, respiratory symptoms such as cough and rhinitis, musculoskeletal pain or paraesthesia. Hypertrichosis (an increased growth rate of existing hair) occurs in approximately 5% of patients.17 There is an increased risk of non-melanoma skin cancer in patients taking ciclosporin who have also had psoralen with ultraviolet light (PUVA) treatment.17,18

Safe prescribing of repeat ciclosporin prescriptions

Key points for safe prescribing include:10, 18

  • Check interactions when initiating other medicines: Ciclosporin is metabolised by cytochrome P450 3A4 and interactions can cause changes in ciclosporin concentrations or the concentration of other medicines. The NZF interactions checker is available at: www.nzf.org.nz/nzf_1. Patients should avoid consuming grapefruit or grapefruit juice as this may increase ciclosporin levels.17
  • Patients should not take ciclosporin if they are also undergoing phototherapy17
  • Immunisation with live vaccines during treatment should be avoided. The efficacy of other vaccinations may be reduced.
  • Discuss contraception and pregnancy plans with female patients: ciclosporin is not contraindicated during pregnancy but has been associated with adverse pregnancy outcomes. Discuss the use of ciclosporin during pregnancy with the patient’s dermatologist. Use during breastfeeding is not advised as infants require monitoring of blood levels of ciclosporin and regular review for signs of toxicity.15
  • Ask patients to report symptoms of infections, e.g. fever, chills, sore throat, mouth ulcers, as these may take longer to clear or increase in severity while taking ciclosporin. Infections may also indicate leucopenia.
  • Ask patients to report symptoms of liver toxicity such as jaundice and abdominal pain

 

Table 2. Suggested monitoring for patients taking ciclosporin.17, 19

Pre-treatment First 3 months Thereafter
Every 2 weeks Monthly Monthly Every 2 months
Laboratory investigations *
Full blood count Tick Tick Tick
Creatinine and electrolytes ** Tick Tick Tick
Liver function tests Tick Tick Tick
Uric acid Tick Tick Tick
Bilirubin Tick Tick Tick
Lipid profile Tick Tick
Pregnancy test Tick
Clinical examination
Blood pressure Tick Tick Tick

* Measurement of magnesium levels is recommended if patients report muscle cramps.19

** Reductions in ciclosporin dose are recommended if signs of nephrotoxicity develop, including elevations in serum creatinine of 30% or more within the normal range; discuss these changes with a dermatologist if they occur.10, 18

Acitretin is an oral retinoid which is typically used in patients with chronic plaque psoriasis if other treatments are not tolerated or have been unsuccessful; it is less effective than methotrexate or ciclosporin and has mucocutaneous adverse effects.20 Acitretin is highly teratogenic and should generally be avoided in women of reproductive age.

Acitretin is fully subsidised with Special Authority approval. Female patients must have been informed of the teratogenic potential of acitretin and agree to use appropriate contraception while taking acitretin as well as for at least two years afterwards.16, 20 Two forms of contraception are recommended, e.g. condoms and an intrauterine device or hormonal contraceptive. In addition, since progesterone-only pills must be taken within a three hour window these are not recommended as one of the forms of contraception.21 Acitretin is teratogenic regardless of the treatment duration or dosage used.20

Monitor patients for elevated triglycerides and lipid levels or altered liver function tests

Frequent monitoring of lipid profile is recommended (Table 3) as up to one-third of patients taking acitretin develop hypertriglyceridaemia or hypercholesterolaemia and patients with psoriasis are already at increased risk of cardiovascular disease.20, 22

Elevations in triglycerides while taking acitretin should be managed by lifestyle changes. Discuss with a dermatologist if a patient meets one of the following criteria:22

  • Five year cardiovascular risk is > 20%
  • Triglyceride levels are ≥ 5.7 mmol/L AND patients have at least one risk factor, e.g.:
    • Elevated blood pressure (> 170/100 mmHg)
    • Angina
    • Ischaemic heart disease
    • Peripheral arterial disease
    • Diabetic nephropathy
    • A total cholesterol:high density lipoprotein ratio > 8
    • A genetic lipid disorder

Depending on a patient’s circumstances, stopping acitretin may be appropriate; changes in lipid profile usually improve four to eight weeks after acitretin is stopped.20

Acitretin causes dryness of mucous membranes

Patients commonly experience dry lips and mouth, and may experience stomatitis, taste disturbances or symptoms such as nose bleeds, rhinitis and dryness of the eyes.20 A topical emollient for dry lips and eye drops can help, especially in patients who use contact lenses.20 Additional emollients may be required for use on areas of dry skin, or topical corticosteroids if patients develop asteatotic dermatitis.

Acitretin can also cause thinning of the skin and nails and alopecia, which can increase sun sensitivity. Thinning of the skin affects the whole body but is particularly noticeable on the palms and soles of the feet, and can be accompanied by redness and scaling. Patients may have difficulty grasping objects or placing pressure on the feet while walking.20 Up to 75% of patients experience some degree of hair loss, with alopecia occurring in 10% of patients.20

Safe prescribing of repeat acitretin prescriptions

  • Ensure females of childbearing potential use two forms of contraception and reinforce the need to avoid pregnancy for at least two years post-treatment23
  • Advise female patients of childbearing potential not to drink alcohol.20, 21 This can increase the metabolism of acitretin into etretinate, which has a half-life of 168 days and contributes to teratogenicity after stopping treatment.17
  • Patients taking acitretin should not donate blood during treatment and for two years following treatment21
  • Tetracyclines should not be used with acitretin as both increase the risk of intracranial hypertension10

 

Table 3. Recommended monitoring for patients taking acitretin17, 20

Pre-treatment First 2 months Thereafter
Every 2 to 4 weeks Every 3 months
Lipid profile Tick Tick Tick
Liver function tests Tick Tick Tick
Full blood count Tick Tick
Creatinine and electrolytes * Tick Tick
Pregnancy test Tick**

* Acitretin use should be avoided in patients with renal impairment10

** Within two weeks of starting treatment; patients should start taking acitretin on the second or third day of the next menstrual cycle10, 20

The TNF inhibitors adalimumab and etanercept are subsidised with Special Authority approval for the treatment of moderate to severe plaque psoriasis.10 Applications for Special Authority approval must be made by a dermatologist and patients must have trialled at least three other treatments of phototherapy, methotrexate, ciclosporin or acitretin, as well as have a psoriasis area and severity index (PASI) score > 15 on treatment.*10 Renewal applications can be made by general practitioners on the recommendation of a dermatologist.

* For further information on the PASI score, see: Chronic plaque psoriasis: an overview of treatment in primary care.

Monitoring recommendations and safe prescribing of repeat prescriptions

Patients should be tested to exclude tuberculosis, HIV, hepatitis B or C, or active infection prior to initiating TNF inhibitor treatment (Table 4).19 Monitoring of full blood count, liver and renal function is required as TNF inhibitors can increase the risk of infections, and have infrequently been associated with thrombocytopenia or leucopoenia, renal impairment, and autoimmune-like syndromes.10, 19

The use of TNF inhibitors is not recommended in patients who have developed cancer within the past five years or in patients with moderate to severe heart failure.10, 24

Injection site reactions and flu-like symptoms are common

TNF inhibitors are administered by subcutaneous injection and pain and irritation at the injection site are reported by 15–37% of patients, usually lasting for three to five days.24, 25 Following a dose patients may develop flu-like symptoms, such as chills, headache, musculoskeletal pain and nausea. Patients typically do not find injection site reactions or flu-like symptoms severe enough to withdraw from treatment and these adverse reactions may improve with subsequent doses.24, 25

Safe prescribing of TNF inhibitors:

  • Women who are pregnant or breastfeeding should not use TNF inhibitors19
  • Immunisation with live vaccines during treatment should be avoided24
  • TNF inhibitors should be withdrawn if patients develop a serious infection, or in patients who have new onset or worsening of heart failure25
  • Advise patients to report worsening fever, sore throat, bruising or bleeding as these may be symptoms of blood disorders such as aplastic anaemia or pancytopaenia10, 24

 

Table 4. Recommended monitoring for patients using TNF inhibitors.19, 24

Pre-treatment Initially after treatment begins Thereafter
4 weeks 12 weeks Every 3 to 6 months
Full blood count Tick Tick Tick Tick
Liver function tests Tick Tick Tick Tick
Creatinine and electrolytes Tick Tick Tick Tick
Pregnancy test Tick
HIV Tick
Hepatitis B & C Tick
Tuberculosis Tick

Acknowledgement:

Thank you to Dr Amanda Oakley, Honorary Associate Professor and Dermatologist, Waikato District Health Board for expert review of this article.


References

  1. Scottish Intercollegiate Guidelines Network (SIGN). Guideline 121: Diagnosis and management of psoriasis and psoriatic arthritis in adults. 2010. Available from: www.sign.ac.uk/guidelines/fulltext/121/index.html (Accessed Jan, 2017).
  2. Chen X, Yang M, Cheng Y, et al. Narrow-band ultraviolet B phototherapy versus broad-band ultraviolet B or psoralen-ultraviolet A photochemotherapy for psoriasis. Cochrane Database Syst Rev 2013;10:CD009481. doi:10.1002/14651858.CD009481.pub2
  3. Paul C, Gallini A, Archier E, et al. Evidence-based recommendations on topical treatment and phototherapy of psoriasis: systematic review and expert opinion of a panel of dermatologists. J Eur Acad Dermatol Venereol 2012;26 Suppl 3:1–10. doi:10.1111/j.1468-3083.2012.04518.x
  4. National Psoriasis Foundation. Light therapy. 2015. Available from: www.psoriasis.org/sites/default/files/light_therapy-12-7-2015.pdf (Accessed Jan, 2017).
  5. Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 5. Guidelines of care for the treatment of psoriasis with phototherapy and photochemotherapy. J Am Acad Dermatol 2010;62:114–35. doi:10.1016/j.jaad.2009.08.026
  6. Mehta D, Lim HW. Ultraviolet B phototherapy for psoriasis: review of practical guidelines. Am J Clin Dermatol 2016;17:125–33. doi:10.1007/s40257-016-0176-6
  7. National Institutes for Health and Care Excellence (NICE). Psoriasis: assessment and management. 2012. Available from: www.nice.org.uk/guidance/cg153 (Accessed Jan, 2017).
  8. Rademaker M, Gupta M, Andrews M, et al. The Australasian Psoriasis Collaboration view on methotrexate for psoriasis in the Australasian setting. Australas J Dermatol 2016; [Epub ahead of print]. doi:10.1111/ajd.12521
  9. Waitemata District Health Board. Methotrexate. Safe prescribing - once a week! 2014. Available from: www.saferx.co.nz/full/methotrexate.pdf (Accessed Jan, 2017).
  10. New Zealand Formulary (NZF). NZF v54. 2016. Available from: www.nzf.org.nz (Accessed Dec, 2016)
  11. Warren RB, Weatherhead SC, Smith CH, et al. British Association of Dermatologists’ guidelines for the safe and effective prescribing of methotrexate for skin disease 2016. Br J Dermatol 2016;175:23–44. doi:10.1111/bjd.14816
  12. Kalb RE, Strober B, Weinstein G, et al. Methotrexate and psoriasis: 2009 National Psoriasis Foundation Consensus Conference. J Am Acad Dermatol 2009;60:824–37. doi:10.1016/j.jaad.2008.11.906
  13. Robinson S, Gibson S, George E, et al. Tolerability and adherence problems in patients on a stable dose of methotrexate: results of a multicentre survey. Musculoskeletal Care 2016;14:152–5. doi:10.1002/msc.1129
  14. Rex Medical Ltd. Trexate New Zealand Datasheet. 2014. Available from: www.medsafe.govt.nz/profs/datasheet/t/trexatetab.pdf (Accessed Jan, 2017).
  15. Butler DC, Heller MM, Murase JE. Safety of dermatologic medications in pregnancy and lactation: Part II. Lactation. J Am Acad Dermatol 2014;70:417.e1-10. doi:10.1016/j.jaad.2013.09.009
  16. Murase JE, Heller MM, Butler DC. Safety of dermatologic medications in pregnancy and lactation: Part I. Pregnancy. J Am Acad Dermatol 2014;70:401.e1-14. doi:10.1016/j.jaad.2013.09.010
  17. Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 4. Guidelines of care for the management and treatment of psoriasis with traditional systemic agents. J Am Acad Dermatol 2009;61:451–85. doi:10.1016/j.jaad.2009.03.027
  18. Rosmarin DM, Lebwohl M, Elewski BE, et al. Cyclosporine and psoriasis: 2008 National Psoriasis Foundation Consensus Conference. J Am Acad Dermatol 2010;62:838–53. doi:10.1016/j.jaad.2009.05.017
  19. Nast A, Gisondi P, Ormerod AD, et al. European S3-Guidelines on the systemic treatment of psoriasis vulgaris. Update 2015. EDF in cooperation with EADV and IPC. Zurich: European Dermatology Forum 2015. Available from: www.euroderm.org/edf/index.php/edf-guidelines/category/5-guidelines-miscellaneous (Accessed Jan, 2017).
  20. Ormerod AD, Campalani E, Goodfield MJD, et al. British Association of Dermatologists guidelines on the efficacy and use of acitretin in dermatology. Br J Dermatol 2010;162:952–63. doi:10.1111/j.1365-2133.2010.09755.x
  21. Douglas Pharmaceuticals Limited. Novatretin datasheet. 2011. Available from: www.medsafe.govt.nz/profs/datasheet/n/novatretincap.pdf (Accessed Feb, 2017).
  22. Chan BCY, Reid N, Armour K, et al. Hypertriglyceridaemia with acitretin use: a proposal for its management in the context of overall cardiovascular risk. Br J Dermatol 2014;171:665–7. doi:10.1111/bjd.13027
  23. Ministry of Health. Application for subsidy by Special Authority. Acitretin. Form SA1476. 2017. Available from: www.pharmac.govt.nz/2017/02/01/SA1476.pdf (Accessed Feb, 2017).
  24. Smith CH, Anstey AV, Barker JNWN, et al. British Association of Dermatologists’ guidelines for biologic interventions for psoriasis 2009. Br J Dermatol 2009;161:987–1019. doi:10.1111/j.1365-2133.2009.09505.x
  25. Menter A, Gottlieb A, Feldman SR, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol 2008;58:826–50. doi:10.1016/j.jaad.2008.02.039
Published: 10 February 2017 | Updated:
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