Azathioprine dosed by thiopurine methyltransferase activity for moderate-to-severe atopic eczema: a double-blind, randomised controlled trial

Meggitt, Simon; Gray, Joanne; Reynolds, Nick J.

doi:10.1016/s0140-6736(06)68340-2

Cited by 260 publications

(242 citation statements)

References 38 publications

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“…The trial by Meggitt and colleagues 399 reported that the most frequent adverse event was nausea, which mainly occurred in participants taking azathioprine (51% of this group) and resulted in seven participants having their doses reduced and four withdrawals in the azathioprine group. Another two participants withdrew from the azathioprine group because of hypersensitivity to the treatment.…”

Section: Harmsmentioning

confidence: 97%

“…In the trial by Meggitt and colleagues, 399 the results for the primary outcome, change in severity of eczema over 12 weeks, showed a 5.4-point (17%) difference [95% CI 1.4 to 9.3 (4.3% to 29%)] in favour of azathioprine. This difference was less than the difference of 30% that the trial was powered to detect, based on pilot studies.…”

Section: Benefitsmentioning

confidence: 99%

“…Two fairly high-quality trials 398,399 comparing azathioprine with placebo in adults, with sufficient power to detect a 25% improvement in SASSAD scores, have shown significant benefit in terms of the severity of eczema and disruption of work/daytime activity. There is not yet any clear evidence of benefit for itching and sleep disturbance, which may be of much more importance to some people with severe eczema when weighed against the potential harms of this treatment.…”

Section: Overall Implications For Research and Practicementioning

confidence: 99%

“…There is not yet any clear evidence of benefit for itching and sleep disturbance, which may be of much more importance to some people with severe eczema when weighed against the potential harms of this treatment. The treatment was only given for 3 months and may not yet have reached its full therapeutic potential, 399 which can be established only by conducting trials over a longer period of time. There is insufficient evidence to deduce whether the benefit provided by azathioprine is equivalent to that provided by methotrexate in adults, as there have not been any non-inferiority or equivalence trials.…”

Section: Overall Implications For Research and Practicementioning

confidence: 99%

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Scoping systematic review of treatments for eczema

Nankervis

Kim

Delamere

et al. 2016

Programme Grants Appl Res

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BackgroundEczema is a very common chronic inflammatory skin condition.ObjectivesTo update the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) systematic review of treatments for atopic eczema, published in 2000, and to inform health-care professionals, commissioners and patients about key treatment developments and research gaps.Data sourcesElectronic databases including MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Skin Group Specialised Register, Latin American and Caribbean Health Sciences Literature (LILACS), Allied and Complementary Medicine Database (AMED) and Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched from the end of 2000 to 31 August 2013. Retrieved articles were used to identify further randomised controlled trials (RCTs).Review methodsStudies were filtered according to inclusion criteria and agreed by consensus in cases of uncertainty. Abstracts were excluded and non-English-language papers were screened by international colleagues and data were extracted. Only RCTs of treatments for eczema were included, as other forms of evidence are associated with higher risks of bias. Inclusion criteria for studies included availability of data relevant to the therapeutic management of eczema; mention of randomisation; comparison of two or more treatments; and prospective data collection. Participants of all ages were included. Eczema diagnosis was determined by a clinician or according to published diagnostic criteria. The risk of bias was assessed using the Cochrane Collaboration risk-of-bias tool. We used a standardised approach to summarising the data and the assessment of risk of bias and we made a clear distinction between what the studies found and our own interpretation of study findings.ResultsOf 7198 references screened, 287 new trials were identified spanning 92 treatments. Trial reporting was generally poor (randomisation method: 2% high, 36% low, 62% unclear risk of bias; allocation concealment: 3% high, 15% low, 82% unclear risk of bias; blinding of the intervention: 15% high, 28% low, 57% unclear risk of bias). Only 22 (8%) trials were considered to be at low risk of bias for all three criteria. There was reasonable evidence of benefit for the topical medications tacrolimus, pimecrolimus and various corticosteroids (with tacrolimus superior to pimecrolimus and corticosteroids) for both treatment and flare prevention; oral ciclosporin; oral azathioprine; narrow band ultraviolet B (UVB) light; Atopiclair™ and education. There was reasonable evidence to suggest no clinically useful benefit for twice-daily compared with once-daily topical corticosteroids; corticosteroids containing antibiotics for non-infected eczema; probiotics; evening primrose and borage oil; ion-exchange water softeners; protease inhibitor SRD441 (Serentis Ltd); furfuryl palmitate in emollient; cipamfylline cream; andMycobacterium vaccaevaccine. Additional research evidence is needed for emollients, bath additives, antibacterials, specialist clothing and complementary and alternative therapies. There was no RCT evidence for topical corticosteroid dilution, impregnated bandages, soap avoidance, bathing frequency or allergy testing.LimitationsThe large scope of the review coupled with the heterogeneity of outcomes precluded formal meta-analyses. Our conclusions are still limited by a profusion of small, poorly reported studies.ConclusionsAlthough the evidence base of RCTs has increased considerably since the last NIHR HTA systematic review, the field is still severely hampered by poor design and reporting problems including failure to register trials and declare primary outcomes, small sample size, short follow-up duration and poor reporting of risk of bias. Key areas for further research identified by the review include the optimum use of emollients, bathing frequency, wash products, allergy testing and antiseptic treatments. Perhaps the greatest benefit identified is the use of twice weekly anti-inflammatory treatment to maintain disease remission. More studies need to be conducted in a primary care setting where most people with eczema are seen in the UK. Future studies need to use the same core set of outcomes that capture patient symptoms, clinical signs, quality of life and the chronic nature of the disease.FundingThe National Institute for Health Research Programme Grants for Applied Research programme.

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Section: Harmsmentioning

confidence: 97%

Section: Benefitsmentioning

confidence: 99%

Section: Overall Implications For Research and Practicementioning

confidence: 99%

Section: Overall Implications For Research and Practicementioning

confidence: 99%

See 2 more Smart Citations

Scoping systematic review of treatments for eczema

Nankervis

Kim

Delamere

et al. 2016

Programme Grants Appl Res

View full text Add to dashboard Cite

show abstract

“…Of note, CyA is rarely effective as monotherapy to completely control AD but topical steroids are usually necessary to reach this goal. Azathioprine is an immunosuppressant drug which has been reported to be effective in severe AD 91,92 . It affects the purine nucleotide synthesis and metabolism and has anti-inflammatory and antiproliferative effects.…”

Section: Systemic Treatmentmentioning

confidence: 99%