Current medical guidelines in the UK for monitoring the side effects of DMARDS cont

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Monitoring[6][17]

The use of disease-modifying anti-rheumatic drugs (DMARDs) is limited by potentially serious side-effects, and therefore patients who are taking these drugs should be monitored on a regular basis as in the table below. Note throughout that, whilst absolute values are useful indicators, trends are also important. Hence any rapid fall or consistent downward trend in any parameter warrants extra vigilance.[6] A useful quick reference guide has been produced by the British Society for Rheumatology. [18]

Rapid falls or consistent downward trends in any parameter are as equally important as absolute values
Penicillamine FBC and stick testing for urine 2-weekly until dose is stable for 3 months, and then monthly.
Gold - intramuscular FBC and urinalysis at the time of each injection.
Chloroquine and hydroxychloroquine Annual review by an optometrist, or by enquiring about visual symptoms, rechecking visual acuity, and assessing for blurred vision using a reading chart.
Sulfasalazine FBC and LFTs monthly for the first 3 months, and 3-monthly thereafter.
Methotrexate FBC fortnightly until 6 weeks after last dose increase; provided it is stable, monthly thereafter until the dose and disease is stable for 1 year. Thereafter, monitoring may be reduced in frequency, based on clinical judgement. LFTs 3-monthly. U&Es 6–12-monthly (more frequently if there is any reason to suspect deteriorating renal function).
Azathioprine FBC and LFTs weekly for 6 weeks and continue every 2 weeks until dose is stable for 6 weeks; then monthly. If maintenance dose is achieved and stable for 6 months, consider discussing with the person to reduce monitoring to 3-monthly. Repeat after dose change, and then monthly. U&Es 6-monthly.
Ciclosporin FBC and LFTs monthly for the first 6 months; then every 8 weeks. U&Es every 2 weeks until dose and trend are stable for 3 months, and then monthly. Watch when a non-steroidal anti-inflammatory drug (NSAID) is added, particularly diclofenac.
Leflunomide FBC, LFTs every month for 6 months and, if stable, 2-monthly thereafter.
Infliximab 1st 2 hours - monitor for acute hypersensitivity reactions (eg chest pain, fever, hypotension, pruritis). Monitor for latent tuberculosis (TB) during treatment and for six months after. FBC, ESR. LFTs and U&Es monthly.
Etanercept Advise patients to report the development of any symptoms of TB or blood dyscrasias after treatment. FBC, ESR. LFTs and U&Es monthly.

Complications and reasons to discontinue drugs[6][8]

Although some have greater tendency than others, all disease-modifying anti-rheumatic drugs (DMARDs) have a potential to cause myelosuppression. Many also cause renal or liver toxicity, skin rash, or gastrointestinal disturbance (see individual drug monographs or summary of product characteristics (SPC) for further details).[19]
Patients should be warned to report any warning symptoms or signs as detailed below:

Symptoms of myelosuppression
  • Sore throat
  • Fever and other signs of infection
  • Unexpected bleeding or bruising
  • Purpura and rashes
  • Mouth ulcers
  • Cough or breathlessness
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Further reading & references

  1. Luqmani R, Hennell S, Estrach C, et al; British Society for Rheumatology and british health professionals in Rheumatology guideline for the management of rheumatoid arthritis (the first two years). Rheumatology (Oxford). 2006 Sep;45(9):1167-9. Epub 2006 Jul 13.
  2. Rheumatoid arthritis, NICE Clinical Guideline (February 2009); Rheumatoid arthritis: the management of rheumatoid arthritis in adults
  3. Management of early rheumatoid arthritis, SIGN (2004)
  4. Rotherham Healthcare Traffic Light Sytem; Rotherham PCT 2007
  5. Akil M, Amos RS; ABC of rheumatology. Rheumatoid arthritis--II: Treatment. BMJ. 1995 Mar 11;310(6980):652-5.
  6. Disease-modifying anti-rheumatic drugs (DMARDs), Clinical Knowledge Summaries (2008)
  7. Felson DT, Anderson JJ, Meenan RF; Use of short-term efficacy/toxicity tradeoffs to select second-line drugs in rheumatoid arthritis. A metaanalysis of published clinical trials. Arthritis Rheum. 1992 Oct;35(10):1117-25. [abstract]
  8. Summary of Product Characteristics (SPC) - methotrexate sodium tablets 2.5 mg, Hospira UK Ltd, electronic Medicines Compendium. Jan 2005
  9. Management of early rheumatoid arthritis, Scottish Intercollegiate Guidelines Network - SIGN (February 2011)
  10. Rheumatoid arthritis - adalimumab, etanercept and infliximab, NICE Technology Appraisal (October 2007); Adalimumab, etanercept and infliximab for the treatment of rheumatoid arthritis
  11. Rheumatoid arthrits (refractory) - rituximab, NICE Technology Appraisal (2007); Rituximab for the treatment of rheumatoid arthritis.
  12. Klareskog L, van der Heijde D, de Jager JP, et al; Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial.; Lancet. 2004 Feb 28;363(9410):675-81. [abstract]
  13. Venkateshan SP, Sidhu S, Malhotra S, et al; Efficacy of Biologicals in the Treatment of Rheumatoid Arthritis. A Meta-Analysis. Pharmacology. 2008 Oct 28;83(1):1-9. [abstract]
  14. Pincus T, O'Dell JR, Kremer JM; Combination therapy with multiple disease-modifying antirheumatic drugs in rheumatoid arthritis: a preventive strategy. Ann Intern Med. 1999 Nov 16;131(10):768-74. [abstract]
  15. Luqmani R, Hennell S, Estrach C, et al; British Society for Rheumatology and British Health Professionals in Rheumatology guideline for the management of rheumatoid arthritis (after the first 2 years). (Oxford). 2009 Apr;48(4):436-9. Epub 2009 Jan 27.
  16. Hosie G, Field M; Shared Care for Rheumatology. Philadelphia:Taylor and Francis; 2002. ISBN 190186510X
  17. Guideline for disease-modifying anti-rheumatic drug (DMARD) therapy, British Society for Rheumatology and British Health Professionals in Rheumatology (2008)
  18. Quick reference guideline for monitoring of disease-modifying anti-rheumatic drug (DMARD) therapy, British Society for Rheumatology (November 2009); To accompany Disease-modifying anti-rheumatic drug therapy guideline of April 2008
  19. Summary of Product Characteristics (SPC) - Remicade® 100 mg powder for concentrate for solution for infusion (infliximab), Schering-Plough Ltd, electronic Medicines Compendium. Updated February 2011
Original Author: Dr Laurence Knott Current Version: Dr Richard Draper
Last Checked: 20/04/2010 Document ID: 533 Version: 6 © EMIS

Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details