Ivermectin and permethrin for treating scabies.

BACKGROUND: Scabies is an intensely itchy parasitic infection of the skin. It occurs worldwide, but is particularly problematic in areas of poor sanitation, overcrowding, and social disruption. In recent years, permethrin and ivermectin have become the most relevant treatment options for scabies. OBJECTIVES: To assess the efficacy and safety of topical permethrin and topical or systemic ivermectin for scabies in people of all ages. SEARCH METHODS: We searched the following databases up to 25 April 2017: the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, and IndMED. We searched the World Health Organization International Clinical Trials Registry Platform, the ISRCTN registry, CenterWatch Clinical Trials Listing, ClinicalTrials.gov, TrialsCentral, and the UK Department of Health National Research Register for ongoing trials. We also searched multiple sources for grey literature and checked reference lists of included studies for additional trials. SELECTION CRITERIA: We included randomized controlled trials that compared permethrin or ivermectin against each other for people with scabies of all ages and either sex. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the identified records, extracted data, and assessed the risk of bias for the included trials.The primary outcome was complete clearance of scabies. Secondary outcomes were number of participants re-treated, number of participants with at least one adverse event, and number of participants withdrawn from study due to an adverse event.We summarized dichotomous outcomes using risk ratios (RR) with 95% confidence intervals (CI). If it was not possible to calculate the point estimate, we described the data qualitatively. Where appropriate, we calculated combined effect estimates using a random-effects model and assessed heterogeneity. We calculated numbers needed to treat for an additional beneficial outcome when we found a difference.We assessed the certainty of the evidence using the GRADE approach. We used the control rate average to provide illustrative clearance rates in the comparison groups. MAIN RESULTS: Fifteen studies (1896 participants) comparing topical permethrin, systemic ivermectin, or topical ivermectin met the inclusion criteria. Overall, the risk of bias in the included trials was moderate: reporting in many studies was poor. Nearly all studies were conducted in South Asia or North Africa, where the disease is more common, and is associated with poverty.EfficacyOral ivermectin (at a standard dose of 200 µg/kg) may lead to slightly lower rates of complete clearance after one week compared to permethrin 5% cream. Using the average clearance rate of 65% in the trials with permethrin, the illustrative clearance with ivermectin is 43% (RR 0.65, 95% CI 0.54 to 0.78; 613 participants, 6 studies; low-certainty evidence). However, by week two there may be little or no difference (illustrative clearance of permethrin 74% compared to ivermectin 68%; RR 0.91, 95% CI 0.76 to 1.08; 459 participants, 5 studies; low-certainty evidence). Treatments with one to three doses of ivermectin or one to three applications of permethrin may lead to little or no difference in rates of complete clearance after four weeks' follow-up (illustrative cures with 1 to 3 applications of permethrin 93% and with 1 to 3 doses of ivermectin 86%; RR 0.92, 95% CI 0.82 to 1.03; 581 participants, 5 studies; low-certainty evidence).After one week of treatment with oral ivermectin at a standard dose of 200 µg/kg or one application of permethrin 5% lotion, there is probably little or no difference in complete clearance rates (illustrative cure rates: permethrin 73%, ivermectin 68%; RR 0.93, 95% CI 0.74 to 1.17; 120 participants, 1 study; moderate-certainty evidence). After two weeks of treatment, one dose of systemic ivermectin compared to one application of permethrin lotion may lead to similar complete clearance rates (extrapolated cure rates: 67% in both groups; RR 1.00, 95% CI 0.78 to 1.29; 120 participants, 1 study; low-certainty evidence).There is probably little or no difference in rates of complete clearance between systemic ivermectin at standard dose and topical ivermectin 1% lotion four weeks after initiation of treatment (illustrative cure rates: oral ivermectin 97%, ivermectin lotion 96%; RR 0.99, 95% CI 0.95 to 1.03; 272 participants, 2 studies; moderate-certainty evidence). Likewise, after four weeks, ivermectin lotion probably leads to little or no difference in rates of complete clearance when compared to permethrin cream (extrapolated cure rates: permethrin cream 94%, ivermectin lotion 96%; RR 1.02, 95% CI 0.96 to 1.08; 210 participants, 1 study; moderate-certainty evidence), and there is little or no difference among systemic ivermectin in different doses (extrapolated cure rates: 2 doses 90%, 1 dose 87%; RR 0.97, 95% CI 0.83 to 1.14; 80 participants, 1 study; high-certainty evidence).SafetyReporting of adverse events in the included studies was suboptimal. No withdrawals due to adverse events occurred in either the systemic ivermectin or the permethrin group (moderate-certainty evidence). Two weeks after treatment initiation, there is probably little or no difference in the proportion of participants treated with systemic ivermectin or permethrin cream who experienced at least one adverse event (55 participants, 1 study; moderate-certainty evidence). After four weeks, ivermectin may lead to a slightly larger proportion of participants with at least one adverse event (extrapolated rates: permethrin 4%, ivermectin 5%; RR 1.30, 95% CI 0.35 to 4.83; 502 participants, 4 studies; low-certainty evidence).Adverse events in participants treated with topical ivermectin were rare and of mild intensity and comparable to those with systemic ivermectin. For this comparison, it is uncertain whether there is any difference in the number of participants with at least one adverse event (very low-certainty evidence). No withdrawals due to adverse events occurred (62 participants, 1 study; moderate-certainty evidence).It is uncertain whether topical ivermectin or permethrin differ in the number of participants with at least one adverse event (very low-certainty evidence). We found no studies comparing systemic ivermectin in different doses that assessed safety outcomes. AUTHORS' CONCLUSIONS: We found that for the most part, there was no difference detected in the efficacy of permethrin compared to systemic or topical ivermectin. Overall, few and mild adverse events were reported. Our confidence in the effect estimates was mostly low to moderate. Poor reporting is a major limitation.

How Much Do We Know about Maintaining Treatment Response after Successful Acne Therapy? Systematic Review on the Efficacy and Safety of Acne Maintenance Therapy.

After cessation of successful initial acne therapy, patients often experience flares. Consecutive maintenance treatment after successful induction therapy is promoted by guidelines; however, little is known about the efficacy/safety of different maintenance regimens. A systematic review on acne maintenance treatments was conducted. We identified 5 randomized controlled trials [RCTs; adapalene vs. vehicle or vs. no treatment (3 RCTs), adapalene/benzoyl peroxide (BPO) vs. vehicle, combination/monotherapy of minocycline (systemic)/tazarotene/placebo] and 3 non-RCTs on systemic isotretinoin, adapalene/BPO and azelaic acid. The results of adapalene versus vehicle/no treatment varied depending on the reported outcome. The 'number of patients maintaining at least 50% improvement' counting inflammatory lesions/non-inflammatory lesions with adapalene was superior to vehicle (risk ratio, RR 1.24, 95% confidence interval, CI 1.08-1.43/RR 1.34, 95% CI 1.18-1.59). However, no significant differences were found in 2 of 3 RCTs for maintaining 'clear/almost clear' or 'mild acne' or on the global grading score. For the combination regimens of minocycline/tazarotene/placebo, no significant differences were found. Adapalene/BPO was superior to vehicle counting inflammatory lesions/non-inflammatory lesions (RR 1.61, 95% CI 1.31-1.99; RR 1.80, 95% CI 1.44-2.26). Due to the scarcity of studies, few conclusions can be drawn. More homogeneous outcome measures and specific maintenance study designs may lead to more robust findings.

Topical treatments for scalp psoriasis.

BACKGROUND: People with chronic plaque psoriasis often have lesions on the scalp. Hair makes the scalp difficult to treat and the adjacent facial skin is particularly sensitive to topical treatments. OBJECTIVES: To assess the efficacy and safety of topical treatments for scalp psoriasis. SEARCH METHODS: We searched the following databases up to August 2015: the Cochrane Skin Group Specialised Register, CENTRAL (2015, Issue 7), MEDLINE (from 1946), EMBASE (from 1974) and LILACS (from 1982). We also searched five trials registers, screened abstracts of six psoriasis-specific conferences and checked the reference lists of included studies for further references to relevant randomised controlled trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) with a parallel-group, cross-over or within-patient design of topical treatments for people of all ages with scalp psoriasis. DATA COLLECTION AND ANALYSIS: Two authors independently carried out study selection, data extraction and 'Risk of bias' assessment. Disagreements were settled by reference to a third author.To assess the quality of evidence, we focused on the following outcomes: 'clearance' or 'response' as assessed by the investigator global assessment (IGA), improvement in quality of life, adverse events requiring withdrawal of treatment and 'response' as assessed by the patient global assessment (PGA).We expressed the results of the single studies as risk ratios (RR) with 95% confidence intervals (CI) for dichotomous outcomes, and mean differences (MD) with 95% CI for continuous outcomes. If studies were sufficiently homogeneous, we meta-analysed the data by using the random-effects model. Where it was not possible to calculate a point estimate for a single study, we described the data qualitatively. We also presented the number needed to treat to benefit (NNTB).We categorised topical corticosteroids according to the German classification of corticosteroid potency as mild, moderate, high and very high. MAIN RESULTS: We included 59 RCTs with a total of 11,561 participants. Thirty studies were either conducted or sponsored by the manufacturer of the study medication. The risk of bias varied considerably among the included studies. For instance, most authors did not state the randomisation method and few addressed allocation concealment. Most findings were limited to short-term treatments, since most studies were conducted for less than six months. Only one trial investigated long-term therapy (12 months). Although we found a wide variety of different interventions, we limited the grading of the quality of evidence to three major comparisons: steroid versus vitamin D, two-compound combination of steroid and vitamin D versus steroid monotherapy and versus vitamin D.In terms of clearance, as assessed by the IGA, steroids were better than vitamin D (RR 1.82; 95% CI 1.52 to 2.18; four studies, 2180 participants, NNTB = 8; 95% CI 7 to 11; moderate quality evidence). Statistically, the two-compound combination was superior to steroid monotherapy, however the additional benefit was small (RR 1.22; 95% CI 1.08 to 1.36; four studies, 2474 participants, NNTB = 17; 95% CI 11 to 41; moderate quality evidence). The two-compound combination was more effective than vitamin D alone (RR 2.28; 95% CI 1.87 to 2.78; four studies, 2008 participants, NNTB = 6; 95% CI 5 to 7; high quality evidence).In terms of treatment response, as assessed by the IGA, corticosteroids were more effective than vitamin D (RR 2.09; 95% CI 1.80 to 2.41; three studies, 1827 participants; NNTB = 4; 95% CI 4 to 5; high quality evidence). The two-compound combination was better than steroid monotherapy, but the additional benefit was small (RR 1.15; 95% CI 1.06 to 1.25; three studies, 2444 participants, NNTB = 13; 95% CI 9 to 24; moderate quality evidence). It was also more effective than vitamin D alone (RR 2.31; 95% CI 1.75 to 3.04; four studies, 2222 participants, NNTB = 3; 95% CI 3 to 4; moderate quality evidence).Reporting of quality of life data was poor and data were insufficient to be included for meta-analysis.Steroids caused fewer withdrawals due to adverse events than vitamin D (RR 0.22; 95% CI 0.11 to 0.42; four studies, 2291 participants; moderate quality evidence). The two-compound combination and steroid monotherapy did not differ in the number of adverse events leading withdrawal (RR 0.88; 95% CI 0.42 to 1.88; three studies, 2433 participants; moderate quality evidence). The two-compound combination led to fewer withdrawals due to adverse events than vitamin D (RR 0.19; 95% CI 0.11 to 0.36; three studies, 1970 participants; high quality evidence). No study reported the type of adverse event requiring withdrawal.In terms of treatment response, as assessed by the PGA, steroids were more effective than vitamin D (RR 1.48; 95% CI 1.28 to 1.72; three studies, 1827 participants; NNTB = 5; 95% CI 5 to 7; moderate quality evidence). Statistically, the two-compound combination was better than steroid monotherapy, however the benefit was not clinically important (RR 1.13; 95% CI 1.06 to 1.20; two studies, 2226 participants; NNTB = 13; 95% CI 9 to 26; high quality evidence). The two-compound combination was more effective than vitamin D (RR 1.76; 95% CI 1.46 to 2.12; four studies, 2222 participants; NNTB = 4; 95% CI 3 to 6; moderate quality evidence).Common adverse events with these three interventions were local irritation, skin pain and folliculitis. Systemic adverse events were rare and probably not drug-related.In addition to the results of the major three comparisons we found that the two-compound combination, steroids and vitamin D monotherapy were more effective than the vehicle. Steroids of moderate, high and very high potency tended to be similarly effective and well tolerated. There are inherent limitations in this review concerning the evaluation of salicylic acid, tar, dithranol or other topical treatments. AUTHORS' CONCLUSIONS: The two-compound combination as well as corticosteroid monotherapy were more effective and safer than vitamin D monotherapy. Given the similar safety profile and only slim benefit of the two-compound combination over the steroid alone, monotherapy with generic topical steroids may be fully acceptable for short-term therapy.Future RCTs should investigate how specific therapies improve the participants' quality of life. Long-term assessments are needed (i.e. 6 to 12 months).

Biosimilars: a systematic review of published and ongoing clinical trials of antipsoriatics in chronic inflammatory diseases.

Biosimilars for psoriasis treatment are currently being developed. Comparison of their efficacy and safety is a challenge. For approval, the European Medicines Agency (EMA) considers indirect evidence from other indications (for example, rheumatoid arthritis) as sufficient. Systematic review of biosimilars for psoriasis and other indications, review of ongoing trials in trial registers. Systematic search for randomized controlled trials (RCT) on biosimilars to adalimumab, etanercept, infliximab, and ustekinumab compared to their reference medication: (1) Publications in Medline, Medline In-Process, Embase, Cochrane Library (efficacy, safety, immunogenicity) and (2) ongoing studies in clinical trial registers. No trials on biosimilars in psoriasis patients were identified. As to the infliximab biosimilar, there is data on patients with ankylosing spondylitis and rheumatoid arthritis, indicating no clinically relevant differences regarding efficacy and safety. Currently, there are two registered studies of an adalimumab biosimilar and one study of an etanercept biosimilar in psoriasis patients. Further ongoing studies on biosimilars to adalimumab, etanercept, and infliximab - all in rheumatoid arthritis patients - were identified. There is currently only limited data regarding RCTs with biosimilars. Provision of further clinical data and inclusion of patients in patient registers will be crucial.

Can physician's self-estimates be used as a valid instrument to determine prescription frequencies of anti-psoriatic drugs? Comparison of the results of a cross-sectional study using self-estimates with actual prescription behavior documented in a cohort study.

PURPOSE: Physicians' self-estimates of their own prescription behavior can be used as a tool to gather information on prescription frequencies. Self-estimates as a tool for health-care research on prescription frequencies need to be validated as a suitable method before it can be used widely. METHODS: We performed a cross-sectional study inviting all dermatologists in Berlin and Brandenburg to give self-estimates of their own prescription behavior of anti-psoriatic drugs. The results were compared with the results from a consecutive 8-months cohort study with the same participants documenting their actual treatment choices during every visit of a psoriasis patient on a standardized documentation sheet. Differences between self-estimates and documented prescription patterns were analyzed with respect to systemic anti-psoriatic drugs and UV treatment. RESULTS: Fifty-one dermatologists participated. They documented an average of 91 patient visits each. Absolute differences between the self-estimates and the documented actual prescription behavior ranged from -2.5% to 1.4% for systemic treatments. For psoralen plus ultravioloet A (PUVA) treatment, the absolute difference was 3.3% and for ultraviolet B (UVB) 4.7%. CONCLUSIONS: Self-estimates were surprisingly exact. Self-estimates may be suggested as one tool to assess prescription frequencies, but further studies are needed to confirm their validity.

Management of anticoagulation during dermatosurgical procedures in Germany - results from a cross-sectional study.

BACKGROUND: Treatment with antiplatelet drugs (APD) and vitamin K antagonists (VKA) can be a challenge during the management of dermatosurgical interventions. METHODS: We performed a cross-sectional study on the perioperative management of APD and VKA in dermatological private practices and clinics in Germany, using anonymized, standardized questionnaires. RESULTS: 233 responses were evaluated (response rate 37 %). Skin biopsies are performed in 82.7 % of offices and in 90.8 % of clinics despite treatment with VKA. Small excisions are done in 62.5 % of offices and 76.9 % of clinics during treatment with VKA, for large excision this applies to 11.9 % of offices and 33.8 % of clinics. Low-dose treatment with APD (#100 mg) does not hinder 80.4 % of private practices and 89.2 % of clinics to perform small excisions as well as 36.3 % and 53.8 %, respectively, to perform large excisions. Of private practitioners 67.3 % and 83.1 % of clinic-based dermato-surgeons do not consider high-dose APD a contraindication for small excisions, and 25.0 % and 41.5 %, respectively, for large excisions. Most frequently switching to heparin is performed 6-8 days prior to surgery and switching back 0-2 days after surgery. CONCLUSIONS: Large differences in the perioperative management of anticoagulant therapy during dermatosurgical procedures have been identified. Further studies and guidelines should be developed.

S3 - Guidelines on the treatment of psoriasis vulgaris (English version). Update.

Psoriasis vulgaris is a common and often chronic inflammatory skin disease. The incidence of psoriasis in Western industrialized countries ranges from 1.5% to 2%. Patients afflicted with severe psoriasis vulgaris may experience a significant reduction in quality of life. Despite the large variety of treatment options available, surveys have shown that patients still do not received optimal treatments. To optimize the treatment of psoriasis in Germany, the Deutsche Dermatologi sche Gesellschaft (DDG) and the Berufsverband Deutscher Dermatologen (BVDD) have initiated a project to develop evidence-based guidelines for the management of psoriasis. They were first published in 2006 and updated in 2011. The Guidelines focus on induction therapy in cases of mild, moderate and severe plaque-type psoriasis in adults including systemic therapy, UV therapy and topical therapies. The therapeutic recommendations were developed based on the results of a systematic literature search and were finalized during a consensus meeting using structured consensus methods (nominal group process).

Disclosure of potential conflicts of interest in dermatological guidelines in Germany - an analysis - status quo and quo vadis.

BACKGROUND: In order to ensure the reliability of clinical practice guidelines it is essential to consider potential conflicts of interest with regard to its development. METHODS: All valid dermatological practice guidelines, which were developed by the German Dermatologic Society (DDG) or the Professional Association of German Dermatologists (BVDD), were recorded. Details about financing and conflicts of interest were systematically evaluated by two independent appraisers according to Domain 6 of the guidelines evaluation instruments AGREE and AGREE II. RESULTS: 38 practice guidelines of the DDG/BVDD were identified. Data about financing of the guidelines are included in 12 of 38 guidelines (32 %) only. Conflicts of interest are stated in no more than 7 of the 38 guidelines (18 %). Wherever a connection with the pharmaceutical industry was stated, no further information on how possible conflicts of interests were dealt with was found. CONCLUSIONS: In current guidelines details on the financing as well as the disclosures of potential conflicts of interest are stated insufficiently. Here an optimization is necessary. Furthermore strategies for handling conflicts of interest need to be developed. One possibility is a specific discussion on this issue at the beginning and during the process of the guidelines work. Furthermore in case of potential conflicts of interest a solution as e. g. abstention from voting on specific questions needs to be developed.

[S3-guidelines for the treatment of psoriasis vulgaris--methods report]. / S3-Leitlinie zur Therapie der Psoriasis vulgaris--Methodenreport.

BACKGROUND: This methods report summarizes the methodology used to update the German Psoriasis Guidelines. METHODS: The guidelines were developed following the recommendations of the Association of the Scientific Medical Societies in Germany. Medline, Cochrane Library and Embase were searched to generate new evidence. In addition, the results from the literature search from the EU Psoriasis Guidelines were used. The recommendations were discussed during a consensus conference using nominal group technique and were voted on during the Delphi procedure. An extensive internal and external review (open) was performed. RESULTS: Due to changes in drug licensing efalizumab was excluded from the guidelines and adalimumab and ustekinumab were added. 97 new studies were included to serve as a basis for the recommendations. The level of evidence improved for calcineurin inhibitors from level 4 to level 2/3 and for MTX and systemic retinoids from level 3 to level 2. A lack of evidence still exists for coal tar (level of evidence 4). All other described interventions have a level of evidence of 2 or 1. CONCLUSIONS: The field of psoriasis therapy is in constant transition. A lack of head to head trials makes direct comparisons still a challenging task. Continuous updating will be necessary to respond to the further changes expected in the field of psoriasis.

A validation study revealed differences in design and performance of search filters for qualitative research in PsycINFO and CINAHL.

OBJECTIVES: Search filters can support qualitative evidence of information retrieval. Various search filters are available for the bibliographic databases PsycINFO and CINAHL. To date, no comparative overview of validation results of search filters verified with an independent gold standard exists. STUDY DESIGN AND SETTING: Identified search filters for PsycINFO and CINAHL were tested for plausibility. Gold standards were generated according to the relative recall approach using references included in an overview of systematic reviews of qualitative studies. All included references were collected and checked for indexing in PsycINFO and CINAHL. Validation tests for each search filter were conducted in both databases to determine whether the references of the gold standards could be retrieved or not. RESULTS: Twelve search filters for PsycINFO and fifteen for CINAHL were validated. The complexity and design of these search filters vary, as well as the validation results for the databases. When locating primary studies of qualitative research, the best sensitivity and precision ratio (among filters with a sensitivity of >80%) was achieved with a filter by McKibbon et al. for PsycINFO and a filter by Wilczynski et al. for CINAHL. CONCLUSION: Project-specific requirements and resources influence the choice of a specific search filter for PsycINFO and CINAHL.

A validation study revealed differences in design and performance of MEDLINE search filters for qualitative research.

OBJECTIVES: Several search filters exist to identify qualitative research, but so far none of them has been validated with an independent set of relevant references irrespective of a medical topic. The objective of this study was to provide a comparative overview of validation results for various MEDLINE search filters. STUDY DESIGN AND SETTING: Search filters were tested for plausibility. A relative recall approach was used to generate a gold standard based on an overview of systematic reviews of qualitative studies. For each review, the included qualitative studies were collected and checked for MEDLINE-indexing. The body of indexed articles yielded the gold standard. Validation tests were conducted to determine whether the references of the gold standard could be identified with the respective search filters. RESULTS: Thirteen search filters were validated in MEDLINE. One search filter by Wong et al. (2004) was found to be the most sensitive (93.63%). While medical subject heading "qualitative research" achieved the best precision (2.15%), sensitivity was the lowest (22.56%). University of Texas provided the best balanced search filter with a sensitivity of 81.96% and a precision of 0.80%. CONCLUSION: Search filters to identify qualitative research in MEDLINE differ greatly in design and performance. The selection of the appropriate search filter depends on project-specific demands and resources.

Evaluation of Ivermectin vs Permethrin for Treating Scabies-Summary of a Cochrane Review.

CLINICAL QUESTION: Is the use of ivermectin in patients infested with scabies associated with improved clinical and safety outcomes compared with permethrin? BOTTOM LINE: Both ivermectin and permethrin treatment were associated with high clearance rates. There is low-certainty evidence that ivermectin was associated with slightly lower rates of complete clearance after 1 week compared with permethrin, 5%, cream (relative risk [RR], 0.65; 95% CI, 0.54-0.78). After 2 weeks, there was no difference in efficacy (RR, 0.91; 95% CI, 0.76-1.08; low-certainty evidence), or in the number of participants with adverse events (week 4: RR, 1.30; 95% CI, 0.35-4.83; low-certainty evidence).

Evidence-based (S3) guidelines for the treatment of psoriasis vulgaris.

Psoriasis vulgaris is a common and often chronic inflammatory skin disease. The incidence of psoriasis in Western industrialized countries ranges from 1 to 2%. Patients afflicted with severe psoriasis vulgaris may experience a significant reduction in quality of life. Despite the large variety of treatment options available, patient surveys have revealed lack of satisfaction with the efficacy of available treatments and a high rate of non-compliance. To optimize the treatment of psoriasis in Germany, the Deutsche Dermatologische Gesellschaft (DDG) and the Berufsverband Deutscher Dermatologen (BVDD) initiated a project to develop evidence-based guidelines for the management of psoriasis. These resulting Guidelines focus on induction therapy in cases of mild, moderate, and severe plaquetype psoriasis in adults. The Guidelines include evidence-based evaluation of the efficacy of all currently available therapeutic options in Germany. In addition, they offer detailed information on how best to administer the various treatments and give information on contraindications, adverse drug reactions, and drug interactions as well as estimates of practicability and cost. The Guidelines were developed following the recommendations of the Arbeitsgemeinschaft wissenschaftlicher medizinischer Fachgesellschaften (AWMF). The therapeutic recommendations were developed by an expert group and finalized during interdisciplinary consensus conferences.

Immune checkpoint blockade for unresectable or metastatic uveal melanoma: A systematic review.

BACKGROUND: The use of immune checkpoint blockade (ICB) for uveal melanoma (UM) is little established. The aim of this review was to provide a comprehensive overview on the efficacy, safety, and tolerability of ICB in patients with UM. METHODS: We performed a systematic literature research covering MEDLINE, Embase and CENTRAL. Abstracts of pertinent conferences and trial registers were handsearched for relevant studies. RESULTS: Out of 1327 records initially identified, 12 eligible studies were included in the qualitative synthesis. They comprised 7 expanded access or named patient programs (n=162), 4 phase II trials (n=171), and 1 phase Ib trial (sample size unknown), while no randomized controlled trial was found. Ipilimumab monotherapy was assessed at 3mg/kg in 5 trials (n=186) with a response rate of 0 to 5%. Two reports investigated ipilimumab at 10mg/kg (n=45) with radiological responses observed in 0 to 6.5%. The median progression-free survival (PFS) was below 3months and the median overall survival was 5.2-9.8months for ipilimumab monotherapy. Severe immune-related adverse events occurred at a frequency comparable to cutaneous melanoma (6 to 36%). Two studies investigated pembrolizumab (2mg/kg) and nivolumab (3mg/kg) with overall response rates of 30% and 6%, respectively. Data on combined ipilimumab and programmed cell death protein 1 inhibition were available from one expanded access program, but no response was observed with a median PFS of 2.9months. CONCLUSIONS: UM is little responsive to ipilimumab regardless of dosage schemes. Sound randomized clinical trials are needed to evaluate the efficacy of combined ICB in patients with UM.