Highlights of the updated Dutch evidence‐ and consensus‐based guideline on psoriasis 2017

Abstract

Linked Comment: Ormerod. Br J Dermatol 2019; 180:11. This is a summary of the 2017 updated Dutch psoriasis guideline, based on the Dutch Society of Dermatology and Venereology guideline on the treatment of psoriasis (2011),1, 2 the European Dermatology Forum (EDF) guideline on the treatment of psoriasis (2015)3 and newer literature. The focus is mainly on patients with moderate-to-severe psoriasis, which is the minority of the total patient population. Topical therapies and phototherapies are outside the scope of this update, but remain important treatment options. We provide sections per drug and patient group, aiming for a useful manual for daily clinical practice, including recommendations for screening and monitoring. In the section on treatment decisions in psoriasis we address the most important aspects of therapeutic decision making. To support dermatologists in making treatment decisions, we provide a concise physician decision aid for the biologics and the small molecule inhibitor apremilast (Table S1; see Supporting Information). The following sections have been updated: systemic therapy (methotrexate, fumarates, adalimumab, etanercept, infliximab, ustekinumab), treatment for paediatric patients, serum concentration and antibody formation in biologics, and quality of life. There are newly added sections on treatment decisions in psoriasis, secukinumab, apremilast, combination therapy, psoriatic arthritis, biosimilars, and pregnancy and biologics. The section on paediatric patients provides guidance on topical therapy and phototherapy in addition to conventional systemic therapy and biologics. We have only included agents that were available in the Netherlands at the start of the update in 2015, meaning that ixekizumab, brodalumab, guselkumab, certolizumab and risankizumab are not included. The sections on retinoids and ciclosporin were not updated; only when strictly necessary minor changes were made, which are clearly indicated in the text. For more detailed information, we refer readers to the full guideline.4 The systematic literature search used for the EDF guideline on the treatment of psoriasis5 was updated until July 2015. For topics that were not covered in the EDF guideline a separate systematic literature search was conducted in MEDLINE, Embase and CENTRAL in July 2015. Details of the search strategies are presented in the full guideline.4 The guideline working group consisted of dermatologists and a rheumatologist, a dermatology nurse and a patient with psoriasis as representatives of their national societies. This working group formulated research questions and outcome measures for the updated and new sections. The outcomes are presented in Table 1. Induction or short-term therapy was defined as 16 weeks, long-term therapy as 24 weeks. Articles were screened for inclusion and exclusion criteria based on the title and abstract by two researchers independently. The full texts were analysed by members of the working group. The risk of bias of the included studies was assessed using the Cochrane Risk of Bias Assessment Tool.6 Data analysis was performed using Review Manager. We added data from the new literature to the EDF analysis, and shared this updated version with the EDF psoriasis guideline working group. The quality of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system for grading evidence7 using GRADEpro GDT online software8 for most sections. Recommendations were formulated by the working group based on the level of evidence according to GRADE. To indicate the strength of the recommendation the formulation in Table 2 was used. The majority of patients with psoriasis have mild disease in which topical therapy is sufficient to suppress the lesions. If necessary, different forms of phototherapy and/or conventional systemic therapy are considered with or without topical agents. With the arrival of biologics, treatment options have increased and the effects of treatments have improved drastically. It can be challenging to choose a suitable therapy for an individual patient. However, we expect that if the treatment is in line with patients’ expectations, preferences and lifestyle, adherence to the treatment and increased treatment satisfaction are more likely.9 We recommend that treatment decisions should therefore be made by patients and physicians together (‘shared decision making’). In our opinion it is important that all agents remain equally accessible and available. A preferred policy for rigid application of one drug is undesirable. We suggest that the following aspects should be addressed in order to choose the best-suiting therapy. These aspects are also summarized in Figure 1. After carefully choosing a therapy, it remains important to check regularly if the treatment still meets the requirements and/or goals. To prevent undertreatment of psoriasis, it is recommended to adapt and follow the treatment goals as described by Mrowietz et al.10 in daily practice (see their Fig. 2): In addition, patients’ satisfaction with treatment should be taken into consideration. To support physicians in the choice of therapy we have developed a physician decision aid (Table S1; see Supporting Information) combining the aspects discussed above. See Table S2 (Supporting Information) for advice on screening and monitoring in systemic therapy. Methotrexate is recommended for both induction and long-term therapy in patients with moderate-to-severe plaque-type psoriasis (Table S3; see Supporting Information). In case of inadequate response (according to the treatment goals), it is recommended to increase the dose from 15 to 30 mg per week. Table S4 details blood tests and their timing. Routine measurement of procollagen III N-terminal peptide is no longer recommended, because of the limited added value in the detection of liver fibrosis compared with alanine transaminase and low specificity of increased procollagen III N-terminal peptide.11 Physicians should be alerted to other risk factors for liver fibrosis (e.g. hepatic steatosis, metabolic syndrome) aside from methotrexate therapy. Monitoring according to Figure 2 is recommended. Recommendations Ciclosporin is recommended as induction therapy in moderate-to-severe plaque-type psoriasis (Table S5; see Supporting Information). Because of its fast-acting effect, ciclosporin is particularly useful for short-term therapy and crisis intervention. Ciclosporin may be prescribed for longer terms (maximum of 2 years) in individual cases, but close monitoring for signs of toxicity such as renal impairment and hypertension is important. Table S6 (see Supporting Information) details blood tests and their timing. Recommendations Acitretin is recommended for induction therapy in moderate-to-severe plaque-type psoriasis, although it is not recommended as a first-choice monotherapy (Table S7; see Supporting Information). In patients with a good clinical effect at the end of induction therapy (16 weeks), maintenance therapy is suggested with the lowest effective dose. Table S8 (see Supporting Information) details blood tests and their timing. Women of childbearing age should not be treated with acitretin because of the teratogenic characteristics of the drug. Contraception is recommended during and up to 3 years after treatment discontinuation (modified in 2017). Fumarates are recommended as induction and long-term therapy for moderate-to-severe plaque-type psoriasis (Table S9; see Supporting Information). In general, the long-term safety profile of fumarates is favourable, but the evidence is relatively limited.12-14 Acetylsalicylic acid (e.g. 80 mg) is suggested to treat flushing as an undesired side-effect of therapy.15 The incidence of progressive multifocal leucoencephalopathy during treatment with fumarates is unknown, but seems related to prolonged periods of lymphocytopenia. In addition to monitoring for lymphocytopenia (Table S10; see Supporting Information), we recommend being alert for neurological symptoms during fumarate therapy and referring a patient to a neurologist if needed. Table S11 (see Supporting Information) details recommended dosing. Recommendations Apremilast is suggested as induction therapy and long-term therapy in moderate-to-severe plaque-type psoriasis (Table S12; see Supporting Information). Long-term safety data are relatively scarce. In patients with severe renal impairment (creatinine clearance < 30 mL min−1) 30 mg once daily is recommended. Table S13 and Table S14 (see Supporting Information) detail blood tests and dosing for apremilast, respectively. Recommendations Adalimumab is recommended as induction therapy and long-term therapy in moderate-to-severe plaque-type psoriasis (Table S15; see Supporting Information). Increasing the dose of adalimumab from 40 mg per 2 weeks to 40 mg per week is suggested for patients with an insufficient response to adalimumab 40 mg per 2 weeks. This dosage increase is according to the label change (November 2015). Table S16 (see Supporting Information) details blood tests for all biologics. Recommendations Etanercept is recommended as induction therapy and long-term therapy in moderate-to-severe plaque-type psoriasis (Table S17; see Supporting Information). A starting dose of 50 mg twice weekly is suggested, over a dose of 50 mg once weekly. Undesired effects of long-term treatment are similar to induction therapy. A maintenance dose of 50 mg twice weekly is suggested over a dose of 50 mg once weekly. Recommendations Infliximab is recommended as induction therapy for chronic plaque-type psoriasis in week 0, 2 and 6 (Table S18; see Supporting Information). Infliximab is recommended as maintenance therapy every 8 weeks (with at least 4 weeks between two administrations). Recommendations Secukinumab is recommended as induction therapy in chronic plaque-type psoriasis (Table S19; see Supporting Information). A dose of 300 mg is recommended over a dose of 150 mg in induction therapy. Secukinumab is suggested for maintenance therapy. Long-term safety data are limited. Recommendations Ustekinumab is recommended as induction therapy in chronic plaque-type psoriasis (Table S20; see Supporting Information). Ustekinumab 45 mg is suggested in patients ≤ 100 kg. Ustekinumab 90 mg is suggested in patients > 100 kg. Ustekinumab is recommended as a maintenance therapy for at least 5 years. The long-term safety profile of ustekinumab over a period of 5 years appears not to be evidently different from that for 1 year in additional literature. Prescription of systemic combination therapy is currently off-label. Patients should be informed about this off-label use and possible side-effects. Therapy should be started only after careful weighing of benefits and risks tailored to the individual patient.16 Etanercept in combination with methotrexate is suggested as induction and maintenance therapy of chronic plaque-type psoriasis. Etanercept in combination with acitretin is suggested as induction and maintenance treatment of chronic plaque-type psoriasis (based on one maintenance study).16 Biologics or methotrexate in combination with ultraviolet B is not recommended as a maintenance treatment in patients with chronic plaque-type psoriasis because of a lack of data on safety.16 Treatment with adalimumab, infliximab, ustekinumab or secukinumab in combination with methotrexate is suggested in treatment-resistant psoriasis. The serum trough level of a biologic depends on many factors, among which are dose and dose frequency, treatment adherence, disease activity, antibody formation and comedication with immunosuppressants. The extent to which the presence or absence of antibodies and the drug serum concentrations correlate to the clinical response depends on the type of biologic and needs further exploration. At the moment a correlation between trough level concentration and clinical effect has only been demonstrated for adalimumab.17 A therapeutic algorithm based on serum trough levels has potential to improve adalimumab therapy, but no prospective studies have been performed yet. It may be useful to determine adalimumab serum trough levels before altering the frequency of administration or stop/switch therapy. A low serum trough level concentration can be caused by antidrug antibodies. The optimal serum trough concentration has been established for adalimumab (3·51–7·00 mg L−1).18 Measurement of only antidrug antibodies provides limited information. Currently approved biosimilars are available for infliximab (Remsima™, Celltrion Healthcare, Budapest, Hungary; Inflectra™, Hospira, Maidenhead, U.K.; and Flixabi®, Biogen Idec, Cambridge, MA, U.S.A.) and for etanercept (Benepali,® Biogen, Cambridge, MA, U.S.A.; and Erelzi, Novartis Pharma AG, Stein, Switzerland). Recommendations There are no major objections to starting a registered biosimilar for patients eligible for biological therapy. It is recommended that patients be included in a registry to monitor efficacy and safety. Substitution of a biologic with a biosimilar in patients who are responding well is not recommended, but the decision to switch to a biosimilar in these patients is reserved for the physician and patient. Physicians should take into consideration that long-term safety data for biosimilars are limited. It is possible for patients who discontinue a biological therapy (for example for more than 6 months) to restart with a biosimilar. In the case of switching to a biosimilar, it is recommended to administer the first dose of the biosimilar when the old reference product was supposed to be re-administered and not before, as the old drug may still be partially present in the body, which makes it impossible to attribute side-effects to either of the two drugs. These recommendations are in line with the Dutch national guideline on biosimilars.19 The following paragraph is based on the Dutch guideline for axial spondyloarthritis (2014)20 and international European League Against Rheumatism (2015)21 and Group for Research and Assessment of Psoriasis and Psoriatic Arthritis guidelines(2016).22 Recommendations As a result of the increased risk in patients with psoriasis, it is recommended that physicians be alert for signs of psoriatic arthritis (PsA): spontaneous persistent pain, swelling or stiffness of one or more joints and nearby ligaments and tendons, or chronic back pain present for at least 3 months before the age of 45 years. It is recommended that patients with psoriasis be referred to a rheumatologist if is a of arthritis, or if have daily chronic back pain for at least 3 months before the age of 45 years. with and with a rheumatologist is recommended not for but also for treatment of Routine additional before to a rheumatologist is not recommended. are recommended as the first in the treatment of The use of is during therapy (Table can be made in (e.g. for and in in with a In patients with therapy, it is recommended that for the be in with a in the of additional measures may be necessary (e.g. in should be before starting immunosuppressants. It is to for at least 4 weeks after a to of in of treated with therapy, as it be necessary to The a should to after biological therapy depends on the of the drug. Recommendations recommendations are summarized in Table We suggest starting or biological therapy in and a pregnancy only if the benefits the risks of In such is a for etanercept the and the relatively low to the It is recommended that biologics be the such as infliximab and adalimumab, before the end of the to the risk of during therapy and at least months after in during therapy and at least months after in during therapy and at least 3 years after on summary of product characteristics and and in 2017 based on recommendations in summary of product measures are because of teratogenic no measures during therapy no measures during therapy and at least 2 weeks after no measures during therapy and at least after during therapy and at least after of during therapy and at least 5 months after no measures during therapy and at least 3 weeks after treatment is and benefits the treatment with etanercept during pregnancy can be considered no measures during therapy and at least 6 months after no measures during therapy and at least weeks after during therapy of during therapy and at least 15 weeks after during therapy of in a treated with a biologic a therefore by a is recommended. It be necessary to administration of and in to biologics in in the patients treated with biologics should be treated in an Data on pregnancy should be in a This section is based on et with more literature. Recommendations Topical are useful in the treatment of paediatric psoriasis, with recommended. on the disease a combination with is recommended. the combination a III it is recommended that this treatment be prescribed only for short-term therapy of 4 if For maintenance therapy are first the effect and side-effects. If necessary a can be in psoriasis, a combination with III is necessary, use is recommended. or is suggested to treat psoriasis of the and If treatment with combination topical or in paediatric psoriasis adherence is in a should be considered before phototherapy or systemic therapy is Recommendations It is recommended that B phototherapy is only used to a limited extent in paediatric psoriasis. It should be used particularly in < years) and in It is the opinion of the guideline working group, that should not be treated with ultraviolet the effect, A therapy is in paediatric psoriasis. Recommendations The effect of in with psoriasis remains In the case of a of and treatment with can be Acitretin is suggested for paediatric psoriasis or Treatment in is because of the teratogenic potential of Ciclosporin is recommended in and for short-term treatment the potential Methotrexate is recommended in a dose between and mg weekly. acid mg 24 after of methotrexate is recommended. If fumarates are used for paediatric psoriasis, one should be of prolonged and follow the recommendations described in the section on fumarates in this Recommendations Biologics should be with in with moderate-to-severe psoriasis the about long-term safety. The working group the conventional In order to long-term it is recommended including treated with a biologic in a Treatment of paediatric patients with psoriasis with biologics should be the of dermatologists with in biological therapy, in For for of of biological therapy in refer to the described for in the sections. It is recommended to check the of (according to the national before starting biological therapy. Etanercept is recommended as an induction and maintenance therapy in and with plaque-type psoriasis from the age of 6 years who are with use or are other systemic agents or is mg to 50 mg per once a week. Adalimumab is recommended as an induction therapy in and 4 years and with plaque-type psoriasis who have an inadequate response to or are for topical therapy and Long-term safety data in are not available. is mg to 40 mg per week 0, 1 and every other week. Ustekinumab is recommended in patients with chronic plaque-type psoriasis from the age of years is with use or who are other systemic agents or Long-term safety data in are not available. The recommended dose for < is mg for with a to ≤ 100 the dose is 45 mg and for patients > 100 the dose is 90 is at week and and every weeks patients with psoriasis an impairment in their quality of and and more compared with Patients with psoriasis in because of and pain, and in including systemic phototherapy and topical therapy have a effect on quality of It is recommended that be to the of psoriasis on quality of in Physicians are possible and to determine quality of by or with the use of such as the or of pain and of can be As patients with psoriasis are it is recommended this be In the case of of it is suggested the patient be referred to a or who can this with about of patients with psoriasis are with their Treatment satisfaction is in patients treated with biologics compared with systemic therapy, phototherapy and topical It is recommended be possible and to treatment satisfaction by patients about their satisfaction with treatment and The Treatment for can be used for this If necessary, treatment should be This summary the most important aspects of systemic therapy in patients with psoriasis. The decision aid for systemic therapies (Table can as a useful for clinical practice, and it also clearly the in signs are described most with the and the Assessment as efficacy outcome However, between studies remains challenging because of the in such as 100 and change in and also the different of (e.g. weeks after start of In addition, in other such as quality of different are such as the and making between studies The of a outcome for psoriasis is recommended by the working group, as this increase the between studies and therefore improve the quality of the We the of patients in treatment To improve shared decision making we are currently a online patient decision aid for psoriasis. 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