Taiwanese Dermatological Association TW PsO consensus boo… · The following panel members were recommended by their respective teaching hospitals and Taiwanese Dermatological Association

T

© 2017 TDA. All Right Reserved.

TaiwaneseDermatological

Association

Consensus Statement onManagement of Psoriasis

出版機關：臺灣皮膚科醫學會（Taiwanese Dermatological Association, TDA）

作者：王莉芳、王德華、李志宏、紀景琪、張雲亭、黃毓惠、楊志勛、蔡呈芳（依姓氏筆劃排列）

地址：台北市中山區 10479 長春路 321 號 10 樓之 1

電話：(02) 2518-5126~7

企劃協力：香港商亞洲醫學有限公司台灣分公司

出版年月：2017 年 6 月 26 日發行第一版

本臨床指引僅供一般建議及參考，每個病人之病情因人而異，確定診斷、治療方式及藥物選擇應由主治醫師因病情而決定治療方式。

版權所有：臺灣皮膚科醫學會（Taiwanese Dermatological Association, TDA）

Taiwanese Dermatological AssociationConsensus Statement on Management of Psoriasis

2

The following panel members were recommended by their respective teaching hospitals

and Taiwanese Dermatological Association to attend the TDA psoriasis consensus meetings held

on, respectively, June 30, 2012, December 22, 2013, and April 12, 2015.

Acknowledgments

理事長

乾癬共識委員會主委

王莉芳醫師（臺大醫院）

蔡呈芳醫師（臺大醫院）

王莉芳醫師（臺大醫院）

王德華醫師（成大醫院）

李志宏醫師（高雄長庚醫院）

紀景琪醫師（林口長庚醫院）

張雲亭醫師（臺北榮民總醫院）

黃毓惠醫師（台北長庚醫院）

楊志勛醫師（台北長庚醫院）

蔡呈芳醫師（臺大醫院）

委員名單（依姓氏筆劃排列）：

3

Introduction

Methods

Tables

Results

Conclusion

References

P.5

P.6

P.7

P.25

P.26

P.13

Contents

DiscussionP.7

● General management 7

● Topical agents 8

● Phototherapy 8

● Nonbiologic systemic agents 9

● Licensed biologic systemic agents 10

● Emerging therapy for psoriasis 11

● Traditional Chinese medicine 13

● Other Taiwanese experience 13

13 General management ●

14 Topical agents ●

17 Phototherapy ●

17 Nonbiologic systemic agents ●

19 Licensed biologic systemic agents ●

21 Emerging therapy for psoriasis ●

23 Combination therapy ●

25 Transitional therapy ●

25 Traditional Chinese medicine ●

4

Introduction

● General management 7

● Topical agents 8

● Phototherapy 8

● Nonbiologic systemic agents 9

● Licensed biologic systemic agents 10

● Emerging therapy for psoriasis 11

● Traditional Chinese medicine 13

● Other Taiwanese experience 13

Psoriasis is a chronic immune-mediated inflammatory disease characterized by abnormal differentiation and hyperproliferation of keratinocytes, which may vary in severity from mild localized plaques to generalized involvement covering nearly the whole body.1 In 2003, a genetic profiling study revealed that psoriasis was strongly associated with HLA-Cw6 in Chinese patients.2 According to two studies conducted based on the Taiwanese National Health Insurance database, the 1-year prevalence rates of psoriasis in Taiwan were estimated to be 0.19% and 0.235%, respectively.3

The Taiwanese National Health Insurance database has enabled research on a wide range of issues regarding the epidemiology of psoriasis. In Taiwan, male patients with psoriasis are put at a higher risk of developing sexual dysfunction, with a hazard ratio of 1.27 (95% confidence interval ): 1.11 - 1.46; P = 0.001];4 whereas in pregnant women with severe psoriasis, an increased risk of low birth weight infants has been found.5 Patients with psoriasis are more likely to suffer from concomitant conditions including chronic diseases such as diabetes, hyperlipidemia, and hypertension,6 and malignant tumors such as non melanoma skin cancer and lymphoma.7 In addition, vitiligo bears significant relation to psoriasis.8 Arthritis is found to be a potential determinant for incident vascular comorbidities in psoriatic patients.9 Among diabetic patients, regular insulin use is associated with development of psoriasis; whereas frequent use of thiazolidinedione may be related to a modest reduction in psoriasis risk.10

The most frequently prescribed category of antipsoriatic medications was topical corticosteroids, and up to 98.4% of patients received such treatment.6 Although no cure is available for psoriasis, many treatment options exist. These include topical agents, phototherapy, and systemic biologic and nonbiologic agents.

Treatment gaps exist in Taiwan in terms of patient expectations of antipsoriatic care in clinical practice. There are also discrepancies between dermatologists when approaching patients in the management of psoriasis. This may have resulted in dermatologists being hesitant about providing the optimal treatment options. In the absence of any local literature that clearly explains the criteria for drug selection, it therefore becomes necessary for experts to come together to discuss the development of clear and definitive local management strategies for psoriasis.

Background

In view of the abovementioned situation, The Taiwanese Dermatological Association set up an Expert Panel, and held consensus meetings three times on, respectively, June 30, 2012, December 22, 2013, and April 12, 2015, to review literature and clinical practice guidelines, in order to reach agreement among Taiwanese dermatologists regarding psoriasis management toward a standardized treatment protocol in Taiwan, with a focus on principles of prescribing, including dosing strategies and safety concerns.

Objectives

5


Methods

To maximize the number of delegates, invitations were extended to all board-certified dermatolo-gists in Taiwan who showed interest in the treatment of psoriasis. They convened to discuss the local management strategies for psoriasis. It was advised that a balance should be achieved between literature evidence and real-life clinical practice.

Six senior dermatologists were invited to present relevant data during each consensus meeting. The topics and discussion points were developed based on premeeting brainstorming among the presenters. To determine the degree of consensus, panel members were requested to vote by using a 1 - 9 numeric rating scale, with a higher score indicating greater level of approval for each given item. An item was deemed to be agreed, if the votes scoring 7 - 9 points accounted for ≥ 75% of the total votes cast, and highly agreed if this figure reached ≥ 90%. In the event that the original version of an item was not approved – i.e., the ratings between 7 and 9 accounted for < 75% of all the votes – amendments to that item were made following which the item was put to the vote once again. Voting on the amended items proceeded on a yes/no basis, with an approval rating of > 50% required for the next round of voting. An amended item, if approved, was then voted upon again using the 1 - 9 scale, with the same rule that the ratings of 7 - 9 should account for ≥ 75% of the votes. However, in case of a < 75% result, or when the votes against the amendment accounted for ≥ 50% in the first place, changes to the given item would be made for the second time. In this way, each item was passed either in its original form or in a certain amended form. A maximum of two amendments were allowed to reach the consensus.

The finalized consensus statements were categorized and tabulated according to general management of psoriasis, and eight categories of antipsoriatic medications: topical agents, phototherapy, nonbiologic systemic agents, licensed biologic systemic agents, newly emerging therapies, combination therapy, transitional therapy, and traditional Chinese medicine.

6

Results

The consensus statements on general management of psoriasis and treatment options, including topical agents, phototherapy, non-biologic systemic agents, licensed biologic systemic agents, newly emerging therapies, combination therapy, transitional therapy, and traditional Chinese medicine are summarized in Tables 1 - 10, respectively. The voting results are given in brackets after each statement. For example, “16 out of 19, 84.2%” means that out of 19 panel members who voted, 16 (84.2%) have graded the statement from 7 to 9. We may also add a symbol of R1 or R2 to the brackets, denoting the number of amendments made to the item discussed before consensus has been achieved. R1 represents one round of amendment, and R2 two rounds.

The consensus statements on general management of psoriasis are shown in Tables 1 and 2, on topical agents in Table 3, on phototherapy in Table 4, on nonbiologic systemic agents in Table 5, on licensed biologic systemic agents in Table 6, on emerging therapy for psoriasis in Table 7, on combination therapy in Table 8, on transitional therapy in Table 9 and on traditional Chinese medicine in Table 10.

7

Discussion

● Most panel members concurred with the classification of psoriasis as set out in Table 1. More members (11 vs. 10) favored including nail lesions as one of the seven types.

● Most panel members did not consider the measurement tools to assess the level of severity of psoriasis11 as convenient and objective.

● Body surface area (BSA), psoriasis area severity index (PASI), and quality of life (QoL) can be used to define mild and moderate to severe psoriasis. Psoriasis can be classed as moderate to severe if mild psoriasis is found concomitant with an exceptional clinical situation. However, the panel did not reach consensus on such clinical situations.

● Although, currently PASI 75 (a 75% reduction in PASI) is used to evaluate treatment success, in Taiwan PASI 50 coupled with improved QoL is still acceptable; however, for patients with moderate to severe psoriasis, the doctor should by all means modify the treatment regimen in case of a PASI of < 50 regardless of QoL.

General management


8

● When addressing the safety concerns of topical steroids in children, to take into account a situation where parents may be hyperreactive, the panel stressed judicious topical steroid use, i.e., appro-priate potency, dosage and treatment duration.

● According to a randomized trial, for scalp psoriasis, the calcipotriol-betamethasone compound gel is more effective than betamethasone alone when evaluated by investigators, but is not more effective when evaluated by patients and using the Total Sign Score.

● When discussing the role of the topical calcineurin inhibitor, the panel members agreed with its application to thinner skin areas such as facial and intertriginous psoriasis.

● Although there was a lack of relevant data regarding the safety of the topical calcineurin inhibitor in pregnancy and lactation, the panel objected to its being completely forbidden in pregnant and breastfeeding women, but accepted its use with caution.

Topical agents

UVB● Determining the initial dose of narrow-band UVB by conducting MED (minimal erythema dose)

testing is no longer usual clinical practice in Taiwan, as this is time consuming and may cause pigmentation. - The MED value in Taiwanese patients is reported as 300 mJ/cm2.12 The Panel agreed on a starting dose of 180 - 350 mJ/cm2. The range was set wider than previously suggested to allow for safe dose escalation at a rate of 10 - 20%.

● In clinical practice in the real-life setting, an alternative method of increasing the dose was added that adopted a fixed increment of 50 - 100 mJ/cm2 each time.

● Some panel members argued that phototherapy was not suitable for children, as they were difficult to immobilize. Instead, children could be directly given biologic agents.

PUVA● There are no 5-methoxypsoralen and trimethylpsoralen in Taiwan; the only available form of psoralen

is 8-methoxypsoralen.

● In Taiwan, the psoralen dose per kilogram of body weight ranges between 0.4 mg and 0.6 mg. It is acceptable to administer 8-methoxypsoralen at a dose of 10 - 40 mg 1 - 2 hours prior to exposure to UVA.

● The starting dose of UVA can be estimated based on the Fitzpatrick scale. The scale is used to classify the response of different types of skin to UV light. As a result, there are six types of skin, namely, types I through VI. The type number divided by 2 yields the starting dose. For example, the starting dose for type IV skin is 2 J/cm2. Usually in Taiwan, the dose ranges between 1 J/cm2 and 2 J/cm2; and an increment of 0.5 - 1 J/cm2 each time is common practice.

● In case of long-term use of psoralen UVA (PUVA), there is an increased risk of photocarcinogenesis in Caucasians with skin types I-III after 200 treatments.13 In Taiwan, long-term PUVA therapy should be also used with caution.

Phototherapy

9

Methotrexate● It is noteworthy that methotrexate (MTX) treatment should be started at a low dose and, if well

tolerated, the dose can be increased in about 1 month.

● PASI 50 is a clinically significant endpoint for the assessment of psoriasis. Failure to achieve PASI 50 means there is a need to increase the dose.

● MTX may persist in the liver for up to 3 months; that is why women are recommended to conceive a child after discontinuation of MTX for 3 months.14

● MTX for the purpose of testing should be given in divided doses every 12 hours or once weekly.

● According to a Taiwanese study, MTX treatment may be associated with reduced risk of developing severe vascular diseases in psoriatic patients without arthritis.9

Acitretin● According to European S3-Guidelines, acitretin should be administered at a dose of 0.3 - 0.5

mg/kg/d.11 However the dosage can reach as high as 1.0 mg/kg/d in Taiwan to treat pustular psoriasis. The panel finally reached a consensus on a dose of 0.3 - 1.0 mg/kg/d.

● Although acitretin may be considered as an effective long-term maintenance agent,15 the specific duration of treatment remains unclear. The use of any dose of acitretin during pregnancy may lead to numerous malformations.15 Where acitretin is used in a woman of childbearing age, potential contraception should be considered and undertaken for 2 years.15 The safety and efficacy of acitretin in children with psoriasis has not been established.

Cyclosporine● Cyclosporine can be used for adults with severe psoriasis and otherwise normal immune systems.

Long-term cyclosporine A (CSA) should be considered with particular caution in patients with cancer or who are immunosuppressed.16 Usually, these patients have failed or are contraindicated to alternative treatments. In Taiwan, the alternative treatments mean phototherapy, MTX, and acitretin. However, cyclosporine can be used as the first-line systemic agent for erythrodermic psoriasis according to the reimbursement guidelines in Taiwan.

● When necessary, CSA may be given to patients responding to treatment continuously for preferably 1 year or up to 2 years. In exceptional cases where no other treatment options are available, treatment with CSA can be extended for longer than 2 years with adequate monitoring.

● Cyclosporine has not been approved to treat pediatric patients with psoriasis. As for pregnancy, this is the safest oral drug ever approved for psoriasis. The National Transplant Pregnancy Registry shows that cyclosporine produces no teratogenic effects, but prematurity and low birth weight;17 moreover, cyclosporine should not be used during pregnancy unless the potential benefit to the mother outweighs the potential risk to the fetus.

Nonbiologic systemic agents


10

Etanercept● Etanercept (ETN) is a type of antitumor necrosis factor alpha (TNFa). Despite being approved for

treatment of psoriasis, TNFα antagonists are also capable of causing immune suppression, resulting in reactivation of microbial infections including tuberculosis and hepatitis B. Surveillance and examination for Hepatitis B virus (HBV) and Mycobacterium prior to starting ETN is warranted in Taiwan.

● Although evidence from clinical trials show that ETN is effective in psoriatic patients older than 4 years, ETN is only approved for use in children aged 6 years and older in Taiwan.18,19 In pregnancy, as long as a conception is confirmed, ETN should be stopped unless the potential benefit outweighs its risk.20

Adalimumab● Adalimumab is indicated in patients with moderate to severe psoriasis who have failed or are intolerant

to systemic treatment or phototherapy [PASI ≥ 10, BSA ≥ 10%, and dermatology life quality index (DLQI) ≥ 10] or in exceptional circumstances where the disease affects high-impact sites (e.g., the face, scalp, palms, soles, flexures and genitals) with impaired psychological and physiological function. Patients can be in remission for a period of time after drug discontinuation.

● The median time to relapse was 141 days (interquartile range, 93 - 202 days). Evidence suggests that the combined use of adalimumab and calcipotriol/betamethasone may be beneficial to patients for rapid and higher efficacy within the first 4 weeks.15 Use of adalimumab involves risks of infection, including tuberculosis, HBV, and hepatitis C virus. A close follow-up for tuberculosis should be maintained during treatment. Biologic therapy should be used with caution in patients with a history of-or even a current-malignancy. Regular assessment for skin cancer including nonmelanocytic skin cancer and melanoma is recommended.21

● Again, a cautious approach to the use of adalimumab should be taken in patients who are planning a pregnancy. During pregnancy, adalimumab should be stopped unless the potential benefit outweighs its risk.

Ustekinumab● In phase III trials, ustekinumab administered at 45 mg or 90 mg (subcutaneous) every 12 weeks

was efficacious for the treatment of moderate-to-severe plaque psoriasis: (1) improvement was seen by Week 4 (after 1 injection)22,23; (2) a maximal response was observed at Week 24 following injections at Weeks 4 and Week 1624,25; (3) at Week 28, around three out of four patients achieved a PASI 75 response; (4) ustekinumab was superior to ETN in terms of clinical response (PASI 75) at 12 weeks.26

● Ustekinumab has not been approved for use in the treatment of erythrodermic psoriasis; however, limited clinical experience showed a suboptimal response compared to plaque type psoriasis.27

Similarly, ustekinumab has not been approved for pustular psoriasis; however, both improvement and aggravation has been reported in case reports.28

Licensed biologic systemic agents

11

● As for long-term tolerability, ustekinumab was well tolerated when administered for up to 76 weeks: adverse event, serious adverse event, and infection rates at 76 weeks were comparable to those seen at 12 weeks; the safety and tolerability profile was comparable to ETN at 12 weeks. The 5-year follow-up data in PHOENIX 1 (A Study of Safety and Effectiveness of Ustekinumab (CNTO 1275) in Patients With Moderate to Severe Plaque-type Psoriasis) are consistent with the previously reported safety findings: ustekinumab is generally welltolerated without evidence of cumulative toxicity with increased duration of exposure.24,25,29,30 Although there is no specific instruction on how long ustekinumab should be used, current published data supports its maintenance of efficacy and safety over up to nearly 5 years after continuous use.

● Ustekinumab should not be used during pregnancy unless the potential benefit to the mother justifies the potential risk to the fetus. Ustekinumab should not be used in children younger than 12 years unless the potential benefit justifies the potential risk when the other treatment choices fail or are not well tolerated.

Tofacitinib● In all countries except Russia, tofacitinib is not approved for use in psoriasis. Administration of

tofacitinib for treating psoriasis will be off-label use.● Tofacitinib may be used in patients ≥ 18 years of age with moderate to severe plaque psoriasis as

determined by: (1) physician’s global assessment of moderate to severe (measured on a 5-point scale); (2) PASI ≥ 10; (3) BSA psoriasis involvement ≥ 10%; and candidates for systemic therapy or phototherapy or who fail or intolerant to systemic treatment or phototherapy (PASI ≥ 10, BSA ≥ 10% and DLQI ≥ 10).31

● In phase III pivotal clinical trials: (1) a consistently higher PASI response is observed in patients receiving 10 mg bid compared to 5 mg bid and to the placebo; (2) clinical efficacy increased steadily until up to 16 - 24 weeks; however longer-term clinical data are still pending. At Week 12, tofacitinib 10 mg bid is noninferior, but tofacitinib 5 mg bid is inferior to ETN 50 mg biw in term of PASI 75 response.31

● In patients who showed PASI 75 response or PGA clear/almost clear at Week 24, median time to loss of a PASI 75 response is 8 weeks, and median time to relapse (defined as loss of > 50% reduction in PASI improvement from baseline) is 16 weeks.31

● Tofacitinib is classified as Class C in pregnancy category. As long as the conception is confirmed, tofacitinib should be stopped unless the potential benefit outweighs its risk to the fetus. Patients on tofacitinib should be monitored for early signs and symptoms of infection, and increased herpes zoster has been observed in patients receiving tofacitinib. Use of tofacitinib, like other biologic therapy, should be cautious in patients with a current or recent history of malignancy; regular assessment for malignancy including nonmelanocytic skin cancer and melanoma is recommended.32

Emerging therapy for psoriasis


12

Infliximab● There are ethnic differences in long-term efficacy of infliximab. In Westerners, there was a tendency

for efficacy to decline; at 50 weeks, 54.5 - 61% achieved PASI 75.33,34 There was no obvious regression in Japanese patients; at 42 - 66 weeks, more than 70% of the participants still achieved PASI 75.35

● Infliximab is only approved for use in ulcerative colitis and Crohn’s disease in Taiwan. Administration of infliximab for treating psoriasis will be off-label use.

● Use of infliximab is associated with an increase in total adverse events, withdrawals due to adverse events, tuberculosis reactivations, and serious infections (e.g., those requiring hospitalization or considered medically important). However, the current evidence shows no associations of infliximab use with an increase in malignancy.36,37

● Because of the long half-life of infliximab, reliable contraception is required in women of childbearing potential until 6 months after the last infusion.16 Infliximab may be used with caution for severe, recalcitrant psoriasis in pregnancy.38 Live vaccines need to be avoided in infants with in utero exposure to infliximab at least the first 6 months of life.39

Secukinumab● The recommended dose of secukinumab is 300 mg by subcutaneous injection with initial dosing

at Week 0, Week 1, Week 2 and Week 3, followed by monthly maintenance dosing starting at Week 4.40 Fifty percent reduction in the mean PASI score occurred at 3.0 weeks with 300 mg and 3.9 weeks with 150 mg. At Week 12, 69.2% of patients on secukinumab 150 mg and 79.4% of patients on 300 mg achieved PASI 75 response; and 59% of patients on secukinumab 300 mg and 39% of patients on 150 mg (39%) achieved PASI 90 response. At 52 weeks, participants in ERA-SURE (Efficacy of Response and Safety of Two Fixed Secukinumab Regimens in Psoriasis) and FIXTURE (Full Year Investigative Examination of Secukinumab vs. Etanercept Using Two Dosing Regimens to Determine Efficacy in Psoriasis) study who were PASI 75 responders at Week 12 maintained their responses in 81 - 84 % of the participants treated with secukinumab 300 mg and in 72 - 82% of participants treated with secukinumab 150 mg.40,41

● Currently available data do not suggest that secukinumab would increase the risk of malignancies. Long-term safety data is still limited.40,41

● There are no adequate and well controlled trials of secukinumab in pregnant women. Secukinumab should be used during pregnancy only if the potential benefit exceeds the potential risk to the fetus.40

Apremilast● Apremilast is associated with a short-term risk of diarrhea, especially when treatment is started,

occurring in approximately 15 - 20% of patients. Tolerability of apremilast is improved by slowly ramping up the dose when treatment is initiated.42

● It is not known whether apremilast or its metabolites are present in human milk; however, apremilast was detected in milk of lactating mice. Because many drugs are present in human milk, caution should be exercised when apremilast is administered to a nursing woman.42

● The safety and effectiveness of apremilast in pediatric ptients younger than18 years have not been established.42

Table 1 Consensus statements on general management of psoriasis.

Main types ofpsoriasis 1

Measurement tools to assess level of severity 11

Classification of severity

How to define mild & moderate to severe psoriasis

How to determine treatment failure or success in moderate tosevere psoriasis 11

Assessment ofnail lesions 45

Plaque, guttate, inverse, pustular (generalized & localized), erythrodermic, psoriatic arthritis (PsA), and psoriatic nail lesions (19/21, 90.5%; R1)

PASI (psoriasis area severity index), percentage of body surface area (BSA), physician’s global assessment (PGA), & quality of life (QoL) (17/19, 89.5%; R1)

● ∆ PASI < 50: modify treatment regimen● ∆ PASI ≥ 50 & < 75, DLQI > 5: modify treatment regimen● ∆ PASI ≥ 50 & < 75, DLQI ≤ 5: continue treatment regimen● ∆ PASI ≥ 75: continue treatment regimen(23/25, 92%)

Currently, mNAPSI (modified nail psoriasis severity index) is a better assessment tool than NAPSI (18/4, 75%); mNAPSI is shown in Table 2.

Psoriasis can be classed as mild and moderate to severe (20/24, 83.3%)

Mild psoriasis can be defined as a percentage of BSA < 10, or a PASI score < 10, and a DLQI score < 10, whereas moderate to severe psoriasis defined as BSA ≥ 10, or a PASI ≥ 10, or a DLQI ≥ 10. DLQI (dermatology life quality index) can be used to assess QoL(21/22, 95.5%; R1)

General managementGeneral management

13

● Numerous Taiwanese patients resort to traditional Chinese medicine for psoriasis treatment; however, its efficacy remains controversial.

● Although the Panel is not very much familiar with traditional Chinese medicine, a consensus has been reached from the perspective of evidence-based medicine.

Traditional Chinese medicine

● Taiwanese dermatologists have conducted numerous research activities and have made significant breakthroughs in psoriasis treatment. Their experience remains to be summed up and did not go through the voting process at the Panel meeting.

● A trial has demonstrated that lindioil is a novel, safe, and effective therapy for treating nail psoriasis.43

● Pulsed dye laser plus topical tazarotene 0.1% cream is an effective and safe therapy in the treatment of nail psoriasis.44

Other Taiwanese experience

Table 2 The modified nail psoriasis severity index (mNAPSI).

Onycholysis and/or the following conditions

Score

Score LeukonychiaSplinterhemorrhages

Red spots in thelunula

Nail bedhyperkeratosis

Subscore:

Subscore:(Maximal 13/finger, maximal 130/10 fingers)Total score:

Nail pitting (n) Crumbling (%) Onycholysis (%)0123

01

NoYes

NoYes

NoYes

NoYes

01 - 1011 - 49

≥ 50

Absent1 - 2526 - 50

> 50

Absent1 - 1011 - 30

> 30

Topical agentsTopical agents

Table 3 Consensus statements on topical agents.

Topical steroids

● Principles of prescribing (20/25, 80%)46,47

- The selection of a corticosteroid with appropriate potency and its vehicle should take into consideration the disease severity, the location being treated, patient preference, as well as the age of the patient.

- Lower potency corticosteroids should be generally preferred for the face, intertrigi-nous areas, areas with thin skin, and in children and the elderly.

- In other areas & in adults, mid- or high-potency agents are generally recom-mended as initial therapy.

- Highly potent corticosteroids could be applied once daily.- There is no difference or only a slight difference between once & twice daily application of potent or moderately potent corticosteroids.

- Long-term use of highly potent corticosteroids should be avoided. Treatment should not be continued for > 4 wks without the patient condition being reviewed

- A gradual reduction in the frequency of usage following clinical response should be instituted.

● Dosage calculations (21/24, 87.5%)- Based on body surface area (Table 214-2 in Fitzpatrick's Dermatology in General Medicine, 7th edition).48

- Based on fingertip units (Table 1 in the AAD guidelines).47

● Safety concerns in pregnancy (19/24, 79.2%).49-51

- Maternal use of topical corticosteroids is not associated with congenital abnor-malities (e.g., orofacial cleft), preterm delivery, & fetal death.

14


Topical steroids(continued)

Vitamin Danalogues

- There is an increased risk of fetal growth restriction associated with maternal use of potent/highly potent topical corticosteroids.

- Mild/moderate potency topical corticosteroids should be used in preference to more potent corticosteroids in pregnancy.

- Potent/highly potent topical corticosteroids should be used as 2nd-line therapy for as short a time as possible, & appropriate obstetric care should be provided as they increase the risk of fetal growth restriction.

- Systemic corticosteroids have greater bioavailability than that of topical cortico-steroids, & thus greater potential for fetotoxicity than topical corticosteroids (systemic corticosteroids are associated with a reduction in fetal birth weight & an increase in preterm delivery), & should not be used preferentially.

● Safety concerns in lactation (17/22, 77.3%)47,52

- The safety of topical steroid use in lactation is unclear, although topical steroids are secreted in breast milk.

- Nursing mothers should not apply topical steroids to their nipples as otherwise the drug may be ingested by the infant during breastfeeding.

- Depending on the class of steroid being used & the duration of therapy, patients should discontinue breastfeeding especially when large amounts of highly potent/ potent topical steroids are applied.

● Safety concerns in children (23/24, 95.8%)47

- Because of a larger skin surface/body mass ratio, the risk of systemic effects to infants & children may be higher as a result of enhanced absorption. Growth retardation is a potential concern when large amounts of potent topical cortico-steroids are used for a long period.

- However, judicious use of topical steroids (i.e., appropriate potency & dosage) does more good than harm to children with psoriasis.

● Efficacy of vitamin D analogues (19/23, 82.6%) 14,53-55

- No differences between calcipotriol & calcitriol.- For psoriatic lesions excluding the scalp & face, the compound of calcipotriol & betamethasone in the form of ointment is more effective than either of the single agents.

- For scalp psoriasis, the calcipotriol-betamethasone compound gel is more effective than calcipotriol alone; but it remains unclear whether the gel is more effective than betamethasone alone.

- The calcipotriol-betamethasone compound ointment may be used to enhance treatment response of biological therapies.

● Use of vitamin D analogues (21/25, 84%) 47,56-58

- Safe upper limit: topical calcipotriol 100 g weekly and topical calcitriol 30 g daily.- The Bureau of National Health Insurance reimburses 30 g of vitamin D analogues per week; however, there may be a quota increase after evaluating the body surface area involved according to the rule of nines.

- No major adverse effects have been found after long-term use of the calcipotriol- betamethasone compound product on an as-needed basis.

- Irritation, folliculitis, & pustular psoriasis may occur following use of the calcipotriol- betamethasone compound product.

15

Vitamin Danalogues(continued)

Tazarotene

Topical calcineurininhibitors

- Although the prescribing information states that the calcipotriol-betamethasone compound product is contraindicated for guttate & pustular psoriasis, there are cases reporting its efficacy & safety in such types of psoriasis; therefore, the product may be used for treating guttate & pustular psoriasis.

● Safety in pregnancy & lactation (no voting result) 47,52,59

- Vitamin D analogues are labeled as FDA Pregnancy Risk Category C.- There are no data on the safety of vitamin D analogues in pregnancy & lactation- Vitamin D analogues are not recommended to be used in pregnancy & lactation, & should only be used when potential benefits outweigh potential harm.

● Safety in children (23/24, 95.8%)- Use of vitamin D analogues appears to be safe in children.

● Use of tazarotene (22/24, 91.7%) 47,52,60

- Applied once daily in the evening.- The most common side effect is skin irritation; so the drug should be applied within the lesional area, avoiding contact with the peripheral healthy skin or skin folds to avoid irritation.

- Tazarotene may be used in combination with moderate or potent topical cortico-steroids to enhance the treatment efficacy & reduce withdrawals.

● Safety in pregnancy & lactation (18/19, 94.7%) 47

- Tazarotene should be avoided in pregnancy (FDA Pregnancy Risk Category X).- Tazarotene is excreted in mammalian milk, but its quantity in human milk is unclear; & there are no human data on its safety in lactation.

● Safety in children (16/18, 88.9%) 47 - No available data in psoriatic patients younger than 18 y.- In the treatment of acne, tazarotene is approved for children aged ≥ 12 y .

● Role of topical calcineurin inhibitors in psoriasis (18/24, 75%) 52,61,62

- Topical calcineurin inhibitors may be used in thinner skin areas such as facial and intertriginous psoriasis.

● Use of topical calcineurin inhibitors (18/24, 75%) 47,52

- Dosing: applied twice daily to affected areas.- The most common side effect is burning & itching that generally subsides with ongoing usage & can also be mitigated by not applying immediately after bathing.

- An increased risk of skin infections owing to interference in the skin’s local immune system.

- Topical calcineurin inhibitors should not be used with phototherapy.● Safety in pregnancy & lactation (19/21, 90.5%; R1) 47,52

- Topical calcineurin inhibitors are labelled as FDA Pregnancy Risk Category C; there are no reports of birth defects related to the use of calcineurin inhibitors.

- Tacrolimus & pimecrolimus are found in human milk.- Given the lack of relevant data, topical calcineurin inhibitors in pregnant or breast-feeding women can only be used when the potential benefits outweigh the risk.

● Safety in children (19/20, 95%) 47

- Not indicated for use in children aged < 2 y.

AAD = American Academy of Dermatology; FDA = Food and Drug Administration.


16

PhototherapyPhototherapy

Table 4 Consensus statements on phototherapy.Candidate forphototherapy

UVB

PUVA

Nonbiologic systemic agentsNonbiologic systemic agents

Table 5 Consensus statements on nonbiologic systemic agents.

Methotrexate (MTX)

● Test dose prior to full treatment schedule (21/25, 84%; R1) 63,64

- Test dose of 2.5 - 5 mg in MTX naïve patients: recommended in those with a decreased glomerular filtration rate or other risk factors for hematologic toxicity (the elderly, drug interactions, hypoalbuminemia, & excessive alcohol intake).

- Laboratory tests should be repeated in 1 wk for hematologic effects.● Initial dose (22/25, 88%) 65-67

- Start with an initial dose of 5 - 7.5 mg weekly with rapid dose escalation to 15 mg/wk by Week 3 or Week 4.

- Start with higher oral dose (15 - 25 mg) weekly when rapid response is desired.

● Systemic psoralen plus UV according to local data (18/18, 100%) 13

- 8-methoxypsoralen, 10 - 40 mg taken 1 - 2 h prior to exposure to UVA.- Avoid sunlight exposure for 12 h after ingestion of psoralen, the use of UV protective eyewear & sunscreen being recommended in daytime when there is risk of UV exposure.

- Starting dose:1 - 2 J/cm2.- Increasing: 0.5 - 1 J/cm2 each time.- Receiving treatment at least twice per week is required to induce clinical remission.

● nbUVB according to local data (19/19, 100%) 13

- Starting dose:180 - 350 mJ/cm2.- Increasing by 10 - 20% each time or a fixed increment of 50 - 100 mJ/cm2.- Usually the final dose should be 5 - 10 times higher than the initial starting dose to achieve clinical remission.

- Receiving treatment at least twice per week is required to induce clinical remission ● If psoriasis has improved by nbUVB (no voting result) 13

- Maintain the same dose & start long-term once-a-week treatment. ● Pregnancy (22/23, 95.7%) 13

- Pregnancy is not a contraindication to the use of UVB therapy.- nbUVB therapy has been used successfully in the treatment of psoriasis in pregnancy.

- nbUVB should be considered as 1st-line therapy in pregnant patients with plaque & guttate psoriasis who need a systemic approach.

● Children (21/21, 100%; R1) 13

- Although there are no studies documenting the long-term safety of UVB photo-therapy in childhood psoriasis, judicious use is reasonable for appropriately selected patients.

Psoriasis patients who have inadequate response to topical agents (18/24, 75%)

nbUVB = narrow-band ultraviolet B; PUVA = psoralen-ultraviolet A.

17

Methotrexate (MTX)

(continued)

Acitretin

Cyclosporine

● Dosing: 0.3 - 1.0 mg/kg/day (19/23, 82.6%). ● Acitretin may be used as an effective long-term maintenance therapy (23/25, 92%;

R2).14

● Pregnancy: FDA Pregnancy Category X (20/25, 80%).15

● Children: no sufficient evidence on safety and efficacy (20/25, 80%).15

● Package insert: indicated to patients with severe psoriasis who have failed or are contraindicated to alternative treatment (22/26, 84.6%).

● Initial dose: 2.5 - 3.0 mg/kg/d (divided in 2 doses), & increased up to 5.0 mg/kg/d if there is < PASI 25 response after 4 wk (28/28, 100%).70

● Discontinued: if there is no response to 5.0 mg/kg/d after 6 wk (28/28, 100%).56

● Maintenance dose: after PASI 75 at 12 wk(1) Controlled by a lower dose (2) Abrupt discontinuation (reinitiated at the previous effective dose once the patient

has a relapse)(3) Weekend therapy (5 mg/kg/d for 2d): delay the onset of relapse without increasing

the side effects (28/28, 100%).71,72

● Expected treatment response (18/21, 85.7%) 65-67

- A 50% reduction in mean PASI has been observed after 7 - 12 wk with a starting dose of 7.5 mg weekly.

- Such reduction could be even achieved within 3 - 4 wk & 75% reduction within 7 wk with a higher starting dose of 15 - 25 mg weekly.

● Maximum dose prior to considering treatment failure (23/25, 92%) 65-67 - If at Week 8, the response is insufficient (PASI, 50 nonresponders), an increase in the dosage to 20 mg/wk can be considered.

- An increase to 25 mg/wk is suggested if the response is insufficient at Week 12.- The clinical response can be expected to reach a maximum within Weeks 12 - 20.- For patients who are nonresponders to 25 mg oral treatment at 16 - 24 wk, the effect of further increasing the dose is unclear.

● Pregnancy: (1) FDA Pregnancy Category X; (2) conceive a child 3 mo after discontinuation of MTX, as 1 cycle of spermatogenesis requires 74 d (no voting result).15

● Children: MTX (dosed at 0.2 - 0.7 mg/kg/wk) provides good clearance or PASI 75 response in most children (22/24, 91.7%).21

● Screening laboratory tests prior to taking MTX: (1) review history of alcohol intake & screening for hepatitis B & C considered when there is evidence of viral hepatitis; (2) CBC count with differential, & testing for creatinine, liver enzymes (ALT, AST, AP, γ-GT), & albumin (25/26, 96.2%; R1).14

● Abnormal liver function: (1) < 2-fold above upper limit of normal level: screening & tests repeated in 2 - 4 wks; (2) > 2-fold but < 3-fold: repeated in 2 - 4 wks & dose reduction; (3) > 3-fold: stop MTX; (4) for persistent elevation that is 3-fold above normal: a liver biopsy is indicated (22/24, 91.7%; R1).68,69

● Prescription of at least 5 mg folic acid /wk within 24 - 48 h after last dose of MTX (no voting result).

● MTX 4 x 2.5 mg tablets /wk can be given in three divided doses every 12 h or as a single dose once weekly (23/24, 95.8%).


18


Table 6 Consensus statements on licensed biologic systemic agents.

Adalimumab

Etanercept (ETN)

● Indications in psoriasis: moderate to severe psoriasis patients who have failed or are intolerant to systemic treatment or phototherapy (23/27, 85%; R1) 77

● Dosing: 80 mg subcutaneously at Week 0, 40 mg at Week 1, & then 40 mg every other week (28/29, 97%)

● Short-term efficacy (onset of action): a significantly higher number of PASI 50 responders is noted at Week 2 (23/26, 88%) the maximal response is between Week 12 & Week16 (18/22, 82%) 78-80

● Long-term efficacy: for PASI 75 responders (at Week 16 & Week 33), the response may decline during Weeks 33 - 52 & is nearly stable in Year 2 & Year 3 (21/27, 78%) 81

● Dosing (21/27, 77.8%) 24,74

- 50 mg biweekly → 25 mg biweekly - 25 mg biweekly continuous usage- 50 mg biweekly → pause until relapse- 50 mg once weekly continuous usage

● Combination with acitretin/nbUVB/MTX: synergistic effects (23/28, 82.1%) 25,29

● Short-term efficacy (onset of action): within 2 - 4 wk (no voting result) 75

● Long-term safety & efficacy of combination of ETN & cyclosporine: not well estab-lished (26/28, 92.9%; R1) 30,76

● Median time to relapse: 85 d (no voting result) 75

● Pregnancy: classified as Class B in Pregnancy Category (21/24, 87.5%; R2)● Children: only approved for use in over-6 years old in Taiwan (21/28, 75%; R2)● Pretreatment screening of HBV (hepatitis B virus) & tuberculosis (19/22, 86.4%)

● Cyclosporine A (CSA) intermittently used for inducing a clinical response with one or several courses over 3 - 6 mo (26/26, 100%).

● CSA may be given to patients responding to treatment continuously for 1 y (preferably) or up to 2 y (26/26, 100%).

● Cyclosporine can be also an alternative for palmoplantar pustulosis, erythrodermic & nail psoriasis; in palmoplantar pustulosis &/or nail psoriasis, cyclosporine can be effective at a low dose, i.e., 2.5 mg/kg/d (25/27, 92.6%).

● Pregnancy: FDA Pregnancy Risk Category C (27/28, 96.4%).● Children: not specifically approved to treat paediatric patients with psoriasis; only

case reports & small case series exist for its use in children; up to 10 mg/kg/d for other indications (26/26, 100%).

● Long-term use of CSA: significant risk of renal toxicity, arterial hypertension, & increased risk of skin cancer especially in patients with extensive previous photo-therapy, i.e., > 200 treatments (26/26, 100%).73

Cyclosporine(continued)


19

ALT= alanine aminotransferase; AP = alkaline phosphatase; AST = aspartate aminotransferase; CBC = complete blood count; FDA = Food and Drug Administration; γ-GT = glutamyltranspeptidase.

Ustekinumab

● Combination with topicals: may be beneficial within the first 4 wk (25/25, 100%; R1) 82

● Risk of infection- Patients on adalimumab should be monitored for early signs & symptoms of infection (20/26, 77%).

- Patients should be fully assessed for both active & latent tuberculosis prior to starting adalimumab (24/27, 89%).

- A close follow-up for tuberculosis should be maintained during treatment (25/27, 93%).

- HBV & HCV (hepatitis C virus) carriers need to be closely followed up for reacti-vation of viral hepatitis (26/29, 90%).

● Risk of malignancy: regular assessment for skin cancer (19/24, 79%; R1) 83

● Pregnancy: Pregnancy Category B by FDA (22/26, 85%)● Children: no safety-relevant data (20/25, 80%); not approved for use in children (no

voting result) 77

● Indications in psoriasis: moderate to severe plaque psoriasis adult patients who are candidates for phototherapy or systemic therapy (no voting result) 84

● Efficacy: effective in the treatment of moderate-to-severe plaque psoriasis at a dose of 45 mg or 90 mg s.c.(subcutaneous) every 12 wk (21/24, 88%) 22,23,26

● Nonplaque psoriasis: not approved (26/29, 90%).● Dose optimization in nonresponders: increasing dose from 45 mg to 90 mg (23/26,

88%) 23,85

● Short-term efficacy (onset of action): within 2 wk (no voting result) 86

● Long-term efficacy: initial clinical responses were generally maintained through Week 244 (no voting result) 87

● Median time to relapse: 15 wk (23/24, 96%) 22

● Treatment duration in responders: maintenance of efficacy & safety over up to nearly 5 y after continuous use (23/23, 100%; R1)

● Short-term tolerability: low rates of serious infections & cardiovascular events at 12 wk (23/25, 92%) 22,23

● Long-term safety & tolerability: well tolerated when administered for up to 76 wk (23/26, 88%) 22,23

● Other safety concerns- Patients should be fully assessed for both active & latent tuberculosis brior to starting ustekinumab (24/25, 96%; R1).

- A close follow-up for tuberculosis should be maintained during treatment (24/25, 96%; R1).

- The safety of ustekinumab in patients who are either HBV or HCV carriers has not been adequately studied (22/25, 88%).

● Pregnancy: Ustekinumab is a Class B (pregnancy classification) drug (26/27, 96%; R1)

● Children: not approved for use in children (younger than 12 years olda) (25/27, 93%; R1)

a Revised to reflect the current status in Taiwan.

Adalimumab(continued)


20

Emerging therapy for psoriasisEmerging therapy for psoriasis

Table 7 Consensus statements on emerging therapy for psoriasis.

Infliximab

Tofacitiniba

● Short-term efficacy: At 10 wk, 68.6 - 80% of the trial participants achieved PASI 75 (14/15, 93.3%)

● Long-term efficacy: ethnic differences (13/14, 92.9%)● Dosing: not approved in Taiwan for psoriasis, off-label use, 5 mg/kg given as an

intravenous induction regimen followed by a maintenance regimen of 5 mg/kg every 8 wk for the treatment of chronic severe plaque psoriasis (12/15, 80%)

● Safety: increase in total adverse events, no association with malignancy (17/17, 100%) 36

● Safety in pregnancy (14/16, 87.5%): 16,38,39,59,89

- Contraception required- Live vaccines need to be avoided in infants

● Candidates: Tofacitinib may be used in (17/18, 94.4%; R1)- Patients ≥ 18 y age with moderate to severe plaque psoriasis as determined by.31

(1) Physician’s Global Assessment (PGA) of moderate to severe (measured on a 5-point scale)

(2) PASI ≥ 10 (3) Body Surface Area (BSA) psoriasis involvement ≥ 10% &

- Are candidates for systemic therapy or phototherapy (16/18, 88.9%; R1)● Efficacy: higher PASI response with 10 mg bid vs. 5 mg bid (17/18, 94.4%)● Dosing: 5 mg bid or 10 mg bid, dose reduction or adjustment needed (16/18,

88.9%)● Efficacy duration (16/18, 88.9%) 88

- Median time to loss of a PASI 75 response: 8 wk- Median time to relapse:16 wk

● Children & pregnancy- Children: safety not established (17/17, 100%)- Pregnancy: Class C in pregnancy category (17/18, 94.4%)

● HBV & TB (17/18, 94.4%):- Surveillance & examination for HBV, HCV& Mycobacterium prior to starting tofacitinib is warranted in Taiwan

- Prophylactic anti-TB treatment should be given for patients with latent TB prior to tofacitinib treatment

● Risk of infection: increased herpes zoster (17/17, 100%)● Risk of malignancies: regular assessment (16/17, 94.1%)● Other safety concerns (18/18, 100%)

- Regular monitoring of hemogram is needed for tofacitinib dose escalation- Elevated serum transaminase & lipid profile has been observed during treatment, which may warrant management

- Asymptomatic serum CPK level has been observed during treatment, but the clinical significance is unknown

21

Apremilast

● Therapeutic indication: Secukinumab is indicated for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy (19/19, 100%)

● Dosage & administration: 300 mg by subcutaneous injection followed by monthly maintenance (18/19, 94.7%)

● Short-term efficacy: at 12 wk 69.2% of patients on secukinumab 150 mg & 79.4% of patients on 300 mg achieved PASI 75 response, 59% of patients on secukinumab 300 mg & 39% of patients on 150 mg achieved PASI 90 response(17 out of 19, 89.5%) 41

● Long-term efficacy: at 52 wk 81 - 84% of the PASI 75 responders at Week 12 maintained a response if treated with secukinumab (300 mg) & 72 - 82% of patients if treated with secukinumab 150 mg (17/19, 89.5%; R1) 41

● Risk of infection- Patients on secukinumab should be monitored for early signs & symptoms of infection (19/19, 100%)

- Patients should be fully assessed for both active & latent tuberculosis prior to starting secukinumab (19/19, 100%)

- A close follow-up for tuberculosis should be maintained during treatment (16/18, 88.9%)

● Risk of malignancy: limited data (17/18, 94.4%)● Pregnancy: Pregnancy Category B by FDA (18/18, 100%)● Children & hepatic/renal dysfunction (17/19, 89.5%)

- Safety & effectiveness of secukinumab in pediatric patients have not been evaluated.

- No formal trial of the effect of hepatic or renal impairment on the pharmacokinetics of secukinumab was conducted.

● Efficacy: Apremilast at 30 mg (bid)/d reached PASI 75 in around 30% at 16 wk (18/19, 94.7%)

● Dosing (18/19, 94.7%)- The recommended dose titration schedule for adults is as follows: (1) Day 1: 10 mg in morning; (2) Day 2: 10 mg in morning & 10 mg in evening; (3) Day 3: 10 mg in morning & 20 mg in evening; (4) Day 4: 20 mg in morning & 20 mg in evening; (5) Day 5: 20 mg in morning & 30 mg in evening; (6) Day 6 & thereafter: 30 mg twice daily.

- Patients with severe renal impairment should receive a half dose.● Side effects (17/19, 89.5%)

- The most common associated side effect is gastrointestinal discomfort.- Depression & weight loss should be cautious in patients taking apremilast.

● Pregnancy & children (19/19, 100%)- Pregnancy category: C.- Nursing mothers: used with caution.- Pediatric use: safety & effectiveness not established.

● Carcinogenesis (19/19, 100%)- There has been no evidence of human or animal data of carcinogenesis by apremilast currently, however, long-term follow-up might be required.

Secukinumab

a Use of tofacitinib in psoriasis is not approved in all countries, except in Russia.


22

Combination therapyCombination therapy

Table 8 Consensus statements on combination therapy.

Acitretin +cyclosporine

Retinoids +topical calcipotriol

Acitretin +topical

corticosteroid

Retinoids +topical agents

Oral retinoids +PUVA

Candidate

● Aciretin +PUVA (22/23, 95.7%) 95

- Controlled data show that the combination of PUVA & retinoid usually achieved disease clearance faster than placebo and PUVA or retinoid monotherapy, & that fewer UVA exposures were needed in the groups that received UVA combined with a retinoid.

● Acetretin + UVB (25/25,100%) 96,97

- Randomaized controlled trials showed that combination therapy with UVB & retinoids had a significantly increased effect on PASI than UVB plus placebo.

● Acitrtin + PUVA vs. Acitretin + nbUVB (19/22, 86.4%) 98,99

- Randomaized trials showed either acitretin + PUVA were equally effective or more effective (66.6% vs. 56.6% complete clearing of psoriasis in one study & 100% vs. 93% satisfactory response in another study) than acitretin + NB-UVB.

● Safety (22/25, 88%; R1): 94

- Given that the altered stratum corneum increases risk of dermatitis because of enhanced penetration of UV light, dosage increases should be done more carefully than with UV monotherapy.

- For UVB phototherapy, exposure should begin with lower UVB dosage to avoid phototoxicity.

● Limited case reports documented about the combination of acitretin + cyclosporine.● In psoriasis patients, an advantage of this combination is: reduce cyclosporine-in-

duced cancers & precancers by retinoids.● Nevertheless, short-term use of this approach is advisable.● Both retinoids & cyclosporine may increase serum cholesterol & triglyceride. (17/20, 85%) 90,91

The cumulative dose of acitretin was lower in the patients who were given combination therapy with topical agents & there was no difference in the rate of side effect (21/22, 95.5%) 94

A double-blind trial showed low-dosage oral retinoids were as effective as high dosage when topical corticosteroids were concomitantly used. Combination therapy with retinoids + topical corticosteroids was associated with greater improvement than topical corticosteroid cream alone or retinoid alone (22/23, 95.7%) 92,93

Randomized trials showed acitretin + calcipotriol exhibited higher complete clearance rate than acitretin monotherapy (21/22, 95.5%) 92,93

Topical, systemic, and phototherapy agents may be used in combination to improve efficacy, optimize the risk-benefit profile, reduce the risk of tolerance & improve long- term disease management (25/26, 96.2%) 90

23

Cyclosporine +PUVA

Cyclosporine +topical agents

● MTX + cyclosporine (19/19, 100%; R1) 100

- Six studies reported on the effect of combining MTX with cyclosporine.- The study by Fraser et al.100 showed a statistically significant difference between groups on PASI & psoriatic arthritis in favour of combination therapy.

- In the 5 remaining uncontrolled studies, a beneficial effect of combining MTX with cyclosporine was reported.

- Increased adverse effects of concurrent use of MTX & cyclosporine.

● The combination of calcipotriol decreased the necessary MTX dose by 3.4 mg/wk & lengthened relapse time following discontinuation of MTX (113 d vs. 35 d) following MTX monotherapy.

● Adverse effects of MTX therapy are reduced by the addition of topical agents primarily because of the lower rates of relapse, thereby decreasing the need for further systemic therapy

(21/23, 91.3%) 101

● MTX + nbUVB (22/23, 95.7%) 102,103

- Patients using UVB–methotrexate combination therapy had a 36% increased likelihood of disease clearance than did patients receiving UVB monotherapy (95% CI, 10% - 63%).

- More rapid clinical improvement, as measured by PASI 75, when compared with nbUVB monotherapy. The mean number of therapy sessions & cumulative dose of UVB required to achieve PASI 75 was significantly less in the combination group (p = 0.001).

● MTX + PUVA (17/19, 89.5%) 104,105

- An additive effect is achieved when combining MTX & phototherapy, but the long-term risk of the skin cancer may be increased & this should be taken into consideration.

- Long-term exposure to PUVA & MTX significantly increases the risk of skin cancer in patients with psoriasis. The ultimate morbidity of these tumors is unde-termined. (relative risk, 2.1 for high vs. low or no exposure to MTX; 95% CI, 1.4 - 2.8). 7 patients had metastatic skin cancer.

● Cyclosporine + topical calcipotriol (20/20, 100%) 106,107

- A double-bind multicenter trial involving 64 patients with severe psoriasis.- Complete clearance or 90 % improvement in PASI score was observed in 50% of patients on combination therapy, compared with 11.8 % on cyclosporine plus placebo ointment.

- In a separate study, combination therapy with topical calcipotriol & cyclosporine was more efficacious than monotherapy in patients with severe psoriasis with nail involvement.

- Compared to the monotherapy, no significant difference in the incidence of adverse effects.

The combination of cyclosporine & UV therapy is not recommended for long-term use because of the increased risk of cancer (20/21, 95.2%; R1) 73,95,108

MTX +systemic agents

MTX +topical calcipotriol

MTX +phototherapy


24CI = confidence interval; PUVA = psoralen-ultraviolet A; UVB = ultraviolet B; nb-UVB = narrow-band ultraviolet B; MTX = Methotrexate; PASI = psoriasis area severity index.

Transitional therapyTransitional therapy

Table 9 Consensus statements on transitional therapy.

Is dosage reductionnecessary in

biologicmonotherapy?

Can biology therapybe discontinued incase of sustained

response?

How to switchbiologicals?

Transitioning from a conventional systemic therapy to a biological agent may be done directly or with a treatment-free period or with an combination if transitioning is required because of lack of efficacy (20/22, 90.9%) 109-111

During successful maintenance with biological monotherapy, a dosage reduction may be considered to limit drug exposure, although this may carry the risk of decreased efficacy & increased risk of antidrug antibody formation (14/18, 77.8%)

● Stopping biological therapy is generally not recommended, given the risk of recurrence or an impact on efficacy following reinitiation of therapy (19/22, 86.4%) 22,112,113

● In clinical trials with primary responding patients, about 20 - 30% fail to regain clinical efficacy after reinitiation of the same biological monotherapy. This decrease in efficacy may be greater with intermittent use of the drug (16/18, 88.9%). 22,112,113

● Lack of response to one biologic does not necessarily predict unresponsiveness to another. Prior treatment failure with an antiTNF drug may be predictors of poor drug survival.

● Switching biologicals for reasons of efficacy should be done without a washout period at the time of the next scheduled dose, but switching for reasons of safety may require a treatment-free interval.

(21/21, 100%)

How should patientsbe transitioned from

a conventionalsystemic therapy to

a biologic agent?

Traditional Chinese medicineTraditional Chinese medicine

Table 10 Consensus statements on traditional Chinese medicine.

In general, the available randomized controlled trials regarding traditional Chinese medicine in treating psoriasis are small and diverse in interventions and outcome measures. At present, we are unable to draw robust conclusions regarding the efficacy of traditional Chinese medicine (12/14, 85.7%)

Use of traditionalChinese medicine

25

Conclusion

The Expert Panel succeeded in developing a set of consensus statements on management strategies of psoriasis, with a focus on assessment of each treatment option, such as principles of prescribing, dosing, efficacy, and safety concerns. Moreover, gaps were identified in certain areas of interest, which indicated possibilities for future clinical dermatology research.

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Taiwanese Dermatological Association TW PsO consensus boo… · The following panel members were recommended by their respective teaching hospitals and Taiwanese Dermatological Association