British Association of Dermatologists’ guidelines for biologic interventions for psoriasis 2009
Authors: C.H. Smith, A.V. Anstey, J.N.W.N. Barker, A.D. Burden, R.J.G. Chalmers, D.A. Chandler, A.Y. Finlay, C.E.M. Griffiths, K. Jackson, N.J. McHugh, K.E. McKenna, N.J. Reynolds, A.D. Ormerod
Journal: British Journal of Dermatology (2009)

Psoriasis is a common, chronic inflammatory skin disease which typically follows a relapsing and remitting course, and is associated with joint disease in approximately 25% of patients.1 The significant reduction in quality of life and the psychosocial disability suffered by patients underline the need for prompt, effective treatment, and long-term disease control (reviewed2, 3). Localized, limited disease can usually be managed satisfactorily with topical agents. Those with moderate to severe disease often require systemic treatment. Phototherapy and traditional 'standard' systemic therapies, while often effective, can be associated with long-term toxicity; some are expensive, and some patients have treatment-resistant disease.4 Also, phototherapy is not available to many due to geographical, logistical or other constraints. Patients themselves demonstrate high levels of dissatisfaction with standard approaches to treatment.5, 6 Biologic therapies for psoriasis utilize molecules designed to block specific molecular steps important in the pathogenesis of psoriasis and now comprise a number of well-established, licensed, treatment options for patients with severe disease. Since 2005, when the British Association of Dermatologists (BAD) first published guidance on the use of biologic therapies in psoriasis,7 much has changed. There is a substantial body of new evidence pertinent to the clinical use of these treatments, the U.K. National Institute for Health and Clinical Excellence (NICE) has approved the use of a number of biologic therapies in severe chronic plaque psoriasis and the BAD Biologic Interventions Register (BADBIR) has been successfully launched. Despite these developments, use of biologic therapy in clinical practice remains limited in the U.K., with a shortfall in funding cited as a significant obstacle to prescribing in approximately 40% of units recently surveyed.8 These guidelines have been revised and updated in accordance with a predetermined scope. This is based on the original scope used in 2005, and extended to include additional areas of practice. Recommendations in this guideline supersede those in the 2005 guideline. The overall objective of these guidelines is to provide up-to-date, evidence-based recommendations on use of biologic therapies (infliximab, adalimumab, etanercept, ustekinumab) in adults and children with all types of psoriasis and, where relevant, psoriatic arthritis, for clinical staff involved in the care of patients treated with biologic therapies. Efalizumab remains in the scope of the guideline in relation to safety only, given that the European Medicines Agency has withdrawn the marketing authorization of this drug because of concerns over the development of progressive multifocal leukoencephalopathy (PML). This guidance does not cover agents licensed outside the U.K. (alefacept) or use of biologic therapies for indications other than psoriasis and psoriatic arthritis. The guideline working group represents all relevant stakeholders including dermatologists, nurses, rheumatologists and patients. Draft guidance was made available for consultation and review by patients, the BAD membership and the British Dermatological Nursing Group (BDNG). Advice relating to tuberculosis was reviewed and approved by the British Thoracic Society. The guideline has been developed using the BAD's recommended methodology9 and with reference to the AGREE (Appraisal of Guidelines Research and Evaluation) instrument.10 Recommendations were developed for implementation in the National Health Service using a process of considered judgment based on the evidence and an awareness of the European product licence of the various treatments. Cochrane, EMBASE and Medline databases were searched between 1990 and June 2009 for clinical trials involving adalimumab, efalizumab, etanercept, infliximab and ustekinumab using an agreed protocol. Two reviewers screened all titles and abstracts independently, and full papers of relevant material were obtained. In relation to efficacy, only randomized controlled trials (RCTs) of high quality (1+ or more; see Appendix 1) were included for chronic plaque psoriasis, whereas in other clinical phenotypes, given the paucity of published data, all data were included. Data from each paper were extracted by two members of the guideline group using standardized literature evaluation forms in order to create evidence tables. Evidence on safety was extracted from literature on use of biologic agents for any indication in view of the relatively limited data specifically relating to use in psoriasis. The methodological limitations of the safety analysis are detailed in section 15. The guideline was peer reviewed by the Clinical Standards Unit of the BAD (made up of the Therapy & Guidelines and Audit & Clinical Standards Subcommittees) prior to publication. These guidelines have been prepared on behalf of the BAD and reflect the best data available at the time the report was prepared. Caution should be exercised in interpreting the data; the results of future studies may require alteration of the conclusions or recommendations in this report. It may be necessary or even desirable to depart from the guidelines in the interests of specific patients and special circumstances. Just as adherence to guidelines may not constitute defence against a claim of negligence, so deviation from them should not necessarily be deemed negligent. This field of psoriasis biologic therapeutics is in a rapid phase of development, and revision of the scope and content of the guidelines will therefore occur on an annual basis. Where necessary, the guideline will be updated via the BAD website, and a fully revised version is planned for 2012. Most patients with moderate to severe disease achieve satisfactory disease control (i.e. significant or complete clearing of disease) in the short term with at least one of the systemic agents currently available.4 Long-term disease control frequently requires some form of continuous therapy and consequent, predictable risks of toxicity. At present, the risks and benefits of biologic therapies relative to standard systemic therapy are largely unknown. Widespread use of these agents in uncomplicated moderate to severe psoriasis is inappropriate and is not supported by the licensed indications for these drugs. Eligibility criteria should encompass both objective measures of disease severity and the impact the disease has on quality of life. All existing disease severity assessment tools are imperfect11-13 and most require some training to complete. The Psoriasis Area and Severity Index (PASI) is a measure of disease severity in chronic plaque psoriasis12 and has been chosen for the purposes of this guideline as it has been widely used in clinical trials including those investigating biologic therapies, and has also been adopted by NICE. A PASI score of ≥ 10 (range 0–72) has been shown to correlate with a number of indicators commonly associated with severe disease such as need for hospital admission or use of systemic therapy,14 and reflects the minimal level of disease severity required for patient inclusion in most of the clinical trials of biologic therapies to date. Where the PASI is not applicable (e.g. pustular psoriasis), body surface area (BSA) affected should be used, with severe disease defined as > 10% BSA affected.14 The Dermatology Life Quality Index (DLQI) is a validated tool for the measurement of quality of life across all skin diseases, including psoriasis, and has been used in both trial and clinical practice settings.13, 15 A score of > 10 (range 0–30) has been shown to correlate with at least 'a very large effect' on an individual's quality of life.12, 14, 16 When using the PASI and DLQI to determine whether or not a patient should be considered for biologic therapy, clinicians should take into account the applicability of these measures to each individual patient. There are circumstances where the use of these tools fails to give a sufficiently accurate assessment of the clinical situation. With respect to the PASI, this is especially pertinent in patients with localized disease that involves special 'high-impact' sites (genitalia, hands, feet, head and neck) where highly significant functional and/or psychosocial morbidity may exist with a PASI < 10. The DLQI may be a poor indicator of emotional disabilities resulting from psoriasis and the validity of the DLQI (and of other quality of life measures) may also be undermined due to linguistic or other communication difficulties.13 Patients with psoriasis may be considered eligible to receive treatment with any of the licensed biologic interventions when they fulfil the eligibility criteria set out below. However, the decision to proceed with treatment must be made in collaboration with the patient and include a careful assessment of the associated risks and benefits17 Eligibility criteria To be considered eligible for treatment, patients must have severe disease as defined in (a) and fulfil one of the clinical categories outlined in (b): (a) Severe disease defined as a PASI score of 10 or more (or a BSA of 10% or greater where PASI is not applicable) and a DLQI > 10. In exceptional circumstances (for example, disease affecting high-impact sites with associated significant functional or psychological morbidity such as acral psoriasis), patients with severe disease may fall outside this definition but should be considered for treatment (Strength of recommendation D; level of evidence 3) AND (b) Fulfil at least one of the following clinical categories (Strength of recommendation D; level of evidence 3, and formal consensus) where phototherapya and alternative standard systemic therapyb are contraindicated or cannot be used due to the development of, or risk of developing, clinically important treatment-related toxicity. are intolerant to standard systemic therapy are unresponsive to standard systemic therapyb have significant, coexistent, unrelated comorbidity which precludes use of systemic agents such as ciclosporin or methotrexate have severe, unstable, life-threatening disease Eligibility criteria for patients with skin and joint disease patients with active psoriatic arthritis or skin disease that fulfils defined British Society for Rheumatology (BSR)18 or BAD guideline criteria, respectively patients with severe skin psoriasis and psoriatic arthritis who have failed or cannot use methotrexate may need to be considered for biologic treatment given the potential benefit of such treatment on both components of psoriatic disease aPhototherapy may be inappropriate in patients (i) who have exceeded safe exposure limits (150–200 treatments for PUVA, 350 treatments for narrowband UVB19, 20), (ii) who are nonresponsive or relapse rapidly, (iii) who have a history of skin cancer or repeated episodes of severe sunburn, (iv) who are intolerant of UV exposure, especially if skin phototype I (sun-sensitive), or (v) for logistical reasons bStandard systemic therapy includes ciclosporin (2·5 mg kg−1 daily; up to 5 mg kg−1 daily), and in men, and women not at risk of pregnancy, methotrexate [single dose (oral, subcutaneous, intramuscular) of 15 mg weekly; max 25 mg weekly] and acitretin (25–50 mg daily) An adequate response to treatment is defined as either (i) a 50% or greater reduction in baseline PASI (PASI 50 response) (or % BSA where the PASI is not applicable) and a 5-point or greater improvement in DLQI4, 21-23or (ii) a 75% reduction in PASI score compared with baseline (PASI 75 response). Initial response to therapy should be assessed at time points appropriate for the drug in question (Table 1). For patients on tumour necrosis factor (TNF) antagonist treatment with psoriasis and psoriatic arthritis, treatment may be continued if there has been a sufficient response in at least one of these components (see BSR guidelines18 for definition of disease response in psoriatic arthritis). TNF is a proinflammatory cytokine produced by a wide variety of cell types including keratinocytes. It plays a central role in the pathogenesis of psoriasis, psoriatic arthritis and a number of other disease states. TNF is released from cells as a soluble cytokine (sTNF) following cleavage from its cell surface-bound precursor (transmembrane TNF, tmTNF). Both sTNF and tmTNF are biologically active, and bind to either of two distinct receptors: TNF receptor 1 (TNFR1, p55) and TNF receptor 2 (TNFR2, p75). This leads to NF-κB activation (which promotes inflammation) and/or cell apoptosis. In addition, tmTNF can itself act as a ligand (via a process of reverse signalling) to induce cell activation, cytokine suppression or apoptosis of the tmTNF-bearing cell. Soluble forms of the TNF receptors also exist and, by binding and neutralizing sTNF, may act as natural TNF antagonists. There are currently two approved groups of biologic agents that target TNF: anti-TNF monoclonal antibodies (adalimumab and infliximab), and sTNF receptors (etanercept). Infliximab is a chimeric human–murine monoclonal antibody (∼ 25% mouse-derived protein) whereas adalimumab is fully human. Etanercept is a genetically engineered fusion protein composed of a dimer of the extracellular portions of human TNFR2 (p75) fused to the Fc domain of human IgG1. All three agents specifically bind both soluble and transmembrane forms of TNF and act by (i) blocking TNFR-mediated mechanisms and (ii) inducing tmTNF (reverse-signalling) events. Etanercept also binds members of the lymphotoxin family [LTα3 (also known as TNF-β) and LTα2β1] although the biological significance of this is unclear. Aside from the latter, there are important differences between the three agents with respect to pharmacokinetics, immunogenicity and structure-based mechanisms of action (only some of which are completely understood).24 It is likely that these differences, in the context of the highly complex biology of TNF, account for observed differences in the efficacy and adverse events profile of TNF antagonists. Lymphocyte function-associated antigen-1 (LFA-1) is a cell surface protein that binds to intracellular adhesion molecule (ICAM) 1–3 and plays a key role in T-lymphocyte recirculation, trafficking to sites of inflammation, antigen presentation by dendritic cells and other activated cells including keratinocytes, and T-cell costimulation. Efalizumab is a recombinant humanized IgG1 monoclonal antibody that binds specifically to the CD11a subunit of LFA-1, which by interfering with LFA-1/ICAM binding inhibits several key steps important in the pathogenesis of psoriasis including T-cell migration into the skin and T-cell activation. More recently, in vivo data have shown that efalizumab induces a state of reversible T-cell 'hyporesponsiveness' including downregulation of a number of T-cell surface molecules unrelated to LFA-1 both in the circulation and in psoriatic plaques.25, 26 Interleukin (IL)-12 and IL-23 are heterodimeric cytokines secreted by activated antigen-presenting cells, and share a common protein subunit, p40. Of relevance to psoriasis, IL-12 activates CD4 and natural killer cells to induce expression of type 1 cytokines (TNF and interferon-γ) while IL-23 stimulates survival and proliferation of a subset of T cells that produce IL-17 (Th17 cells). Recent immunological27 and genetic studies indicate a central role for IL-23 in the pathogenesis of psoriasis.28Ustekinumab is a fully human IgG1κ monoclonal antibody which acts as an IL inhibitor by binding with high affinity and specificity to the p40 protein subunit. It thus prevents IL-12 and IL-23 from binding to their IL-12Rβ1 receptor protein expressed on the surface of immune cells. Three large RCTs demonstrate that etanercept is effective in chronic plaque psoriasis.29-31 Onset of action is slower than that seen with the monoclonal antibodies, with clinically significant improvement in disease severity scores evident between 4 and 8 weeks after initiation of treatment.30 Response is dose related, with 34% (25 mg biweekly) and 48% (50 mg biweekly) of patients achieving PASI 75 by 12 weeks (Table 2). Continuing therapy up to 6 months improves response rates further (43% and 57% for 25 mg biweekly and 50 mg biweekly, respectively).29, 30, 32 While there are no RCT data establishing efficacy beyond 6 months, data from a 2-year, open-label etanercept 50 mg biweekly extension study32 (following the phase III study reported by Tyring et al.31) suggest that efficacy is maintained for up to 1 year, with approximately 75% of patients maintaining their PASI 75 response over the ensuing year. Overall, continuous therapy provides better disease control and higher levels of patient satisfaction compared with interrupted therapy. When treatment is stopped, disease relapses slowly: median time to disease relapse as defined by loss of PASI 50 in those who achieved PASI 75 after 24 weeks of continuous etanercept 25 or 50 mg biweekly, was 85 and 91 days, respectively, with no evidence of disease rebound. On re-treatment, mean PASI scores were similar, with the majority of patients achieving equivalent efficacy after 12 further weeks (i.e. 56% and 60% of PASI 75 responders achieved this level of efficacy on re-treatment).33, 34 Aside from objective measures of disease improvement (PASI, physician's global assessments), studies also report associated clinically meaningful improvements in quality of life measures,35-37 reduction in fatigue and depression,31 and increased proportions of patients in paid employment.38, 39Post hoc analysis of two of these RCTs demonstrated that response rates in those over 65 years were the same as those under 65 years, although numbers in the older age group were small (n = 77).40 The 25 mg twice weekly and 50 mg once weekly dosing regimens are probably interchangeable given that their pharmacokinetic profiles are comparable,41 that the number of patients achieving PASI 75 at 12 weeks following etanercept 50 mg weekly (in an RCT setting compared with placebo)42 was comparable with that seen in other RCTs investigating etanercept 25 mg biweekly and that no significant differences were observed in mean PASI or DLQI in a cohort of patients receiving open-label etanercept 25 mg biweekly (at week 24) and etanercept 50 mg once weekly (at week 36).43 In the RCTs cited, the frequency of adverse events or serious adverse events in patients receiving etanercept was no greater than in the control patients, with the exception of injection site reactions. One small (n = 20 in each treatment arm) RCT has shown superior efficacy of etanercept 25 mg once weekly compared with acitretin 0·4 mg kg−1 daily at 24 weeks (see below).44 Given the role of TNF in adipocyte homeostasis, elevated levels of TNF in obese patients, and the fixed (nonweight adjusted) dosing regimen used for etanercept, decreased response rates may occur in heavier patients, particularly with low-dose etanercept. This is supported, in part, by pharmacological modelling (using published RCT data)45 and data cited in the study by de Groot et al.46 The combination of etanercept and methotrexate has been shown to be more effective in rheumatoid arthritis (RA) than either agent alone, with no significant additional toxicity. Limited data suggest that the addition of methotrexate may also confer improved etanercept efficacy in psoriasis. A small RCT (n = 59) investigated the efficacy and safety of introducing etanercept (25 mg biweekly) in patients already established on methotrexate, and reported significantly increased numbers of patients 'clear or nearly clear' at 24 weeks on combination therapy, as compared with those in whom methotrexate was discontinued.47 A retrospective case series (n = 14) reported both improved efficacy with the introduction of methotrexate in patients on etanercept and loss of efficacy on withdrawal of methotrexate from patients on combination therapy.48 Data from a small RCT (n = 60) reported that the combination of etanercept 25 mg once weekly with acitretin 0·4 mg kg−1 daily is as effective as etanercept 25 mg twice weekly, and that both these interventions are more effective that acitretin alone.44 These early data would suggest that in the short term at least, the combination may offer additional efficacy but, perhaps as importantly, there is no additional associated toxicity. The patient cohort in the cited RCTs may not be representative of patients likely to be treated in clinical practice as entry to the studies required patients only to be considered suitable for, or have previously had, PUVA or systemic therapy. However, objective disease severity criteria were the same as those currently recommended by the BAD and NICE, and mean PASI scores on entry to studies were significantly higher (ranging from 16 to 18). Prospective case cohort studies of 'real life' practice report comparable response rates in 'high-need' patients who have previously failed multiple systemic therapies, all of which suggests that data from the RCTs can be extrapolated to clinical practice.46, 49, 50 There is a lack of long-term RCT data beyond 6 months, and only limited data on re-treatment (of the two published studies available,34, 51 one is open label,34 and both report outcome following one repeat cycle of treatment only). Existing RCT data indicate that 50 mg biweekly is more effective than 25 mg biweekly, but there are no trial data indicating whether increasing the dose to 50 mg biweekly in patients who fail to achieve or maintain adequate responses on 25 mg biweekly results in improved disease control. This is especially pertinent given NICE guidance which currently limits treatment to the 25 mg biweekly dose (see below). Etanercept is licensed for use in moderate to severe psoriasis at either 50 or 25 mg biweekly for the first 3 months, and 25 mg biweekly thereafter, for up to 24 weeks. Continuous therapy beyond 24 weeks may be appropriate for some adult patients (SPC). NICE has approved use of etanercept in severe plaque psoriasis (subject to defined disease severity) at the 25 mg biweekly dose only, and did not find the 50 mg twice weekly dose cost effective, with therapy to be continued only in those patients achieving disease response at 3 months (Table 1). • Etanercept is recommended for the treatment of patients with severe psoriasis who fulfil the stated disease severity criteria – refer to section 8.0 (Strength of recommendation A; level of evidence 1++) • Etanercept therapy may be initiated at either 50 or 25 mg twice weekly and disease response assessed at 3–4 months (Strength of recommendation A; level of evidence 1++) • The choice of which dose to use will depend on clinical need, disease severity, body weight and, in the U.K., the dose that will be funded (Strength of recommendation B; level of evidence 1++) • Patients established on etanercept 25 mg twice weekly may wish to consider switching to etanercept 50 mg once weekly as these two dosing regimens are equivalent in terms of efficacy (Strength of recommendation A; level of evidence 1+) • In patients who respond, treatment may be continued according to clinical need, although long-term data on efficacy are limited to 2 years (Strength of recommendation C; level of evidence 2+) • Treatment may be discontinued without risk of disease rebound, although there may be a lower response rate on restarting therapy (Strength of recommendation B; level of evidence 1+) • Methotrexate may be recommended comedication in certain clinical circumstances, e.g. where it is required for associated arthropathy, or to improve efficacy (Strength of recommendation B; level of evidence 1+) Three large RCTs52-54 indicate that infliximab therapy is highly effective in chronic plaque psoriasis (Table 252-56). Onset of action is rapid, with evidence of significant improvement within the first 2 weeks of treatment and maximum benefit by week 10 when 79% of patients achieve PASI 75 (Table 2) (and mean drop in DLQI of 1054, 57). This response is largely maintained over time with 74%53 and 53% achieving PASI 75 at 6 and 12 months, respectively (Table 2). Loss of efficacy correlates with development of antibodies to infliximab, which occurs in 19% of patients treated.53 One RCT54 (n = 835) investigated continuous vs. intermittent therapy (3 and 5 mg kg−1) following a standard induction course (at 0, 2 and 6 weeks); continuous therapy at 5 mg kg−1 every 8 weeks achieved optimal control. Time to relapse in the intermittent arm (defined by loss of PASI 75) was stated as being 'between week 14 and 22 in the majority of patients' although data were not shown.54 An early (small) dose-finding study58 indicated that 50% (15/30) patients relapse (loss of PASI 75) by week 26. There are no published prospective trial data beyond 1 year. One study prospectively assessed nail disease during therapy53 using the Nail Psoriasis Severity Index (NAPSI) to assess a target, worst affected, nail: a 26·8% improvement in NAPSI from baseline was observed at week 10 with a maximum of 57·2% improvement reported at week 24. This was maintained until week 50. Numbers of patients with complete clearance of nail disease (from the target nail) continued to improve between weeks 24 and 50 (26·2% and 44·7%, respectively). There are no RCT data on use of methotrexate in combination with infliximab in psoriasis. In both RA and psoriatic arthritis, cotherapy with methotrexate is a licensed recommendation, and response rates (with and without methotrexate) are at least comparable in these disease indications. Higher serum levels of infliximab have been reported with methotrexate coadministration which may in part explain reports of improved efficacy. Methotrexate (low dose, 7·5 mg weekly) also reduces the incidence of antibodies to infliximab.59-61 The patient cohort in the cited RCTs may not be representative of patients likely to be treated in clinical practice. The mean PASI at baseline was ≥ 10 in all the studies cited. However, failure of previous systemic therapy was not an entry criterion, in that most studies required patients to be candidates for systemic therapy and/or failed topicals only. A subanalysis of patients in the study by Menter et al.54 (continuous vs. intermittent) did, however, indicate that baseline PASI (< 20 vs. > 20) and the nature of previous treatments (including two or more systemic therapies, or biologic therapy) had no effect on treatment response. The design of the study investigating continuous vs. intermittent infliximab therapy is problematic in that study visits occurred at monthly intervals: hence patients randomized to receive intermittent therapy could potentially receive infliximab at 4-weekly intervals (if PASI 75 was not maintained), and cumulative doses in both arms were reported as similar. Infliximab is licensed for use (5 mg kg−1 every 8 weeks) in moderate to severe plaque psoriasis. NICE has approved use of infliximab in patients with 'very severe disease' (sic) (PASI ≥ 20, DLQI ≥ 18) with treatment beyond 10 weeks recommended only in those who achieve certain response criteria. • Infliximab is recommended for the treatment of patients with severe psoriasis who fulfil the stated disease severity criteria – refer to section 8·0 (Strength of recommendation A; level of evidence 1++) • Infliximab therapy should be initiated at a dose of 5 mg kg−1 at weeks 0, 2 and 6 and disease response assessed at 3 months (Strength of recommendation A; level of evidence 1++) • In patients who respond, subsequent infusions (5 mg kg−1) should be given at 8-week intervals to maintain disease control although long-term data are available only up to 1 year (Strength of recommendation A; level of evidence 1++) • Interrupted therapy should be avoided given the associated increased risk of infusion reactions and poorer disease control (Strength of recommendation A; level of evidence 1+) • Methotrexate may be recommended comedication in certain clinical circumstances, e.g. where it is required for associated arthropathy, to improve efficacy or to reduce the development of antibodies to infliximab (Strength of recommendation D; level of evidence 3) Three large RCTs demonstrate that adalimumab is a highly effective treatment for chronic plaque psoriasis (Table 2).62-64 Onset of action is rapid, with significant improvements in disease severity evident within 2 weeks of treatment initiation62 and maximal disease response seen between weeks 12 and 16. Response is dose related with 69% of patients achieving PASI 75 at week 12 with adalimumab 40 mg every other week62-65 (i.e. the licensed dose for psoriasis), and 80% achieving PASI 75 with adalimumab 40 mg weekly.62 Clinically relevant improvements in health-related quality of life indicators are also reported.66 In one study,62 a small subset of patients (n = 34) who had failed to achieve PASI 50 following at least 24 weeks of adalimumab every other week was escalated to the weekly dose for the remaining duration of the 60-week study (open-label); 40% of this cohort recorded PASI 50 responses, suggesting that dose escalation may further improve efficacy. Efficacy data are available up to 1 year, with no evidence of significant loss of response over time in those patients who respond and are continued on treatment.63 Loss of response on stopping treatment was also investigated in the third phase of the study reported by Menter et al.;63 those who had maintained PASI 75 by week 33 were re-randomized to receive either placebo or a further 19 weeks of adalimumab (double blind). While mean time to relapse was not reported, 28% of patients receiving placebo relapsed (< PASI 50 response relative to baseline with a minimum of a 6-point increase in PASI score relative to week 33) compared with 5% relapse in those continuing on adalimumab by week 52. As part of this study, patients who