Meloxicam in acute UV dermatitis — a pilot study

The non-steroidal anti-inflammatory drug (NSAID) meloxicam is a preferential cyclooxygenase-2 (COX-2) antagonist. The UV protective potential of this drug was studied to compare it with the reported beneficial effects of such preferentially COX-1 specific NSAIDs as indomethacin and acetylsalicylic acid in the literature. In a pilot study (open-label, non-randomized, non-controlled, unblinded), 10 patients received UV irradiation with the minimal erythema dose (MED), first with meloxicam (7.5 mg/die) to reduce post-operative pain and second without ingestion of meloxicam. The factor of UV protection was evaluated. In six of ten patients meloxicam showed no benefit, whereas four of ten patients had a 1.3- up to 3-fold UV protection. In this study, the benefit in UV protection of meloxicam as a prefential COX-2 antagonist was not above the reported benefit of the "old" COX-1 inhibiting NSAIDS.     

Safety of selective cyclooxygenase-2 inhibitors and a basic non-steroidal anti-inflammatory drug (NSAID) in Japanese patients with NSAID-induced urticaria and/or angioedema: Comparison of meloxicam, etodolac and tiaramide

The identification of a safe and reliable alternative for patients with non-steroidal anti-inflammatory drug (NSAID)-induced urticaria/angioedema is a frequent problem for dermatologists and other practitioners. Cyclooxygenase-2 (COX-2) inhibitors have been reported to be safe for NSAID-intolerant patients from the US and Europe but not all of them have yet been approved for use in Japan. It was our objective to investigate the clinical manifestations of oral NSAID challenges in Japanese patients with histories of urticaria and/or angioedema after the intake of NSAIDs and to find safe alternative drugs, including COX-2 inhibitors and a basic anti-inflammatory drug. Twenty subjects suspected NSAID-induced urticaria/angioedema from histories were included in a double-blind or single-blind, placebo-controlled oral challenge protocol using NSAIDs. Skin prick tests using NSAIDs, which were dissolved in saline, were conducted. The mean age of the patients was 37.3 years; 14 patients were female. The results of other challenge tests showed that the most frequently intolerated drugs was loxoprofen (100%), followed by acetyl salicylic (94.4%), etodolac (53.3%), dicrofenac (50%), acetaminophen (38.5%), meloxicam (33%), and tiaramide (21.4%). Urticaria and angioedema were induced after aspirin intake in 83.3% and 22.2% of patients, respectively, whereas an asthmatic response was seen in 5.6%. Skin prick tests with NSAIDs were 100% negative. This study showed that among the NSAIDs that are available in Japan and that were investigated in this study, tiaramide, which does not inhibit COX, is the relatively safe alternative drug for Japanese patients with NSAID-induced urtiacaria and/or angioedema. Furthermore, meloxicam seems to be better tolerated than etodolac between two selective COX-2 inhibitors.     

Etoricoxib challenge in patients with chronic urticaria with NSAID intolerance

Patients with chronic urticaria frequently experience flares of hives following the ingestion of chemically unrelated nonsteroidal anti-inflammatory drugs (NSAIDs). The pathogenic mechanism of these reactions is based on cyclooxygenase-1 (COX-1) enzyme inhibition. In most cases, nonselective NSAIDs, which inhibit both COX-1 and COX-2, are responsible for such adverse reactions; in contrast, analgesic and anti-inflammatory drugs exerting limited inhibition on COX-1 are generally better tolerated by these patients. This study aimed to detect tolerability of etoricoxib, a selective COX-2-inhibiting drug, in patients with chronic urticaria with a history of NSAID intolerance. Single-blind, placebo-controlled oral challenges with increasing doses of etoricoxib were carried out in 17 adult patients with chronic urticaria exacerbated by NSAID. All patients tolerated the drug at therapeutic doses. The study suggests that etoricoxib, with its favourable COX-1/COX-2 ratio, is well tolerated by patients with chronic urticaria exacerbated by NSAID intolerance.     

The treatment of moderate to severe psoriasis with a new anti-CD11a monoclonal antibody

BACKGROUND: Anti-CD11a (hu1124) is a humanized monoclonal antibody directed against the CD11a subunit of LFA-1. This study investigated whether treatment with anti-CD11a antibody provides clinical benefit to patients with moderate to severe plaque psoriasis. METHODS: This was a double-blind, placebo-controlled, phase II, multicenter study. In total, 145 patients with minimum Psoriasis Area and Severity Index scores of 12 and affected body surface area of 10% or more were sequentially enrolled into low-dose (0.1 mg/kg, n = 22) or high-dose (0.3 mg/kg, n = 75) groups. Within groups, patients were randomized to treatment or placebo (n = 48) in a 2:1 ratio. Drug was administered intravenously at weekly intervals for 8 weeks. RESULTS: The percentage of subjects achieving more than 50% improvement in physician's global assessment at day 56 (1 week after final dose) was 15% and 48% for placebo and 0.3 mg/kg of drug, respectively (P =.002). A physician's global assessment of excellent (>75% improvement) was greater in the 0.3 mg/kg group versus placebo (25% vs 2%, P =.0003). Average Psoriasis Area and Severity Index scores at day 56 were 13.9 +/- 7.5 (placebo) and 10.9 +/- 8.4 (0.3 mg/kg) (P <.0001). Epidermal thickness was reduced in the 0.3 mg/kg group compared with the placebo group (37% vs 19%, P =.004). Treatment was well tolerated; mild to moderate flu-like complaints were the most common adverse events. White blood cell counts and lymphocyte counts transiently increased. Depletion of circulating lymphocytes did not occur. CONCLUSIONS: Anti-CD11a antibody administered intravenously in 8 weekly doses of 0.3 mg/kg was well tolerated and induced clinical and histologic improvements in psoriasis.     

Positive patch test reactions to celecoxib may be due to irritation and do not correlate with the results of oral provocation

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among those therapeutics most frequently causing pseudoallergic and sometimes allergic cutaneous adverse reactions. Coxibs preferentially inhibiting cyclooxygenase-2 are increasingly propagated as alternatives in NSAID-sensitive patients. We evaluated the tolerability of celecoxib in NSAID-sensitive patients. In 14 consecutive patients (6 males, 8 females, age 18-72 years), scratch and patch tests with homogenized Celebrex were performed, followed by single-blind, placebo-controlled oral provocation (maximal single dose: 200 mg; cumulative dose: 350 mg). 8 of the first 10 patients showed erythematous reactions to celecoxib on patch testing after 2 days with decrescendo kinetics between then and day 3. 9 patients with no history of NSAID intolerance showed similar reactions. When the patch tests were repeated with homogenized Celebrex at final concentrations of 5% and 10% in petrolatum, no reaction was observed in any patient. Subsequent oral provocation was tolerated without adverse effects by all individuals. We conclude that patch tests with high concentrations of celecoxib cause irritant reactions and do not correlate with the outcome of oral provocation tests. Therefore, these tests should be performed with lower concentrations of celecoxib (Celebrex). Celecoxib itself seems to be a valuable alternative drug in NSAID-sensitive patients.     

Phase I/II study of the oral retinoid X receptor agonist bexarotene in Japanese patients with cutaneous T‐cell lymphomas

Safety, tolerability, pharmacokinetics and efficacy of bexarotene, a novel retinoid X receptor (RXR)‐selective retinoid, were evaluated in Japanese patients with stage IIB–IVB and relapsed/refractory stage IB–IIA cutaneous T‐cell lymphomas (CTCL). This study was conducted as a multicenter, open‐label, historically controlled, single‐arm phase I/II study. Bexarotene was p.o. administrated once daily at a dose of 300 mg/m² for 24 weeks in 13 patients, following an evaluation of safety and tolerability for 4 weeks at a dose of 150 mg/m² in three patients. Eight of 13 patients (61.5%) with an initial dose of 300 mg/m² met the response criteria using the modified severity‐weighted assessment tool (mSWAT) at 24 weeks or discontinuation. Dose‐limiting toxic effects (DLT) were present in four of 13 patients (31%) at a dose of 300 mg/m²: two neutropenia, one abnormal hepatic function and one hypertriglyceridemia. No DLT was observed in patients received 150 mg/m² bexarotene. In the 13 patients at 300 mg/m², common drug‐related adverse events (AE) included hypothyroidism (92%), hypercholesterolemia (77%), leukopenia or neutropenia (39%), nasopharyngitis or anemia (31%). The treatment‐related grade 3 AE included hypertriglyceridemia (4/16 patients, 25%), increased alanine aminotransferase, increased aspartate aminotransferase, dyslipidaemia, leukopenia and neutropenia (1/16 patients, 6%), and one of 16 patients experienced grade 4 hypertriglyceridemia. No patients discontinued bexarotene due to the AE during the study, but dose reduction or suspension was required. Bexarotene was shown to be well tolerated at 300 mg/m² once daily and effective in Japanese patients with CTCL.     

Guselkumab,an anti‐interleukin‐23 monoclonal antibody,for the treatment of moderate to severe plaque‐type psoriasis in Japanese patients: Efficacy and safety results from a phase 3, randomized,double‐blind,placebo‐controlled study

Previous global studies of guselkumab have demonstrated clinical benefits in patients with psoriasis. The aim of this 52‐week, phase 3 study was to evaluate efficacy and safety of guselkumab in Japanese patients with moderate to severe plaque‐type psoriasis. Patients randomly received guselkumab 50 mg or 100 mg at weeks 0, 4 and every 8 weeks, or placebo with cross‐over to guselkumab 50 mg or 100 mg at week 16. Co‐primary end‐points were the proportion of patients achieving Investigator's Global Assessment (IGA) cleared/minimal (0/1) and 90% or more improvement in Psoriasis Area and Severity Index (PASI‐90) at week 16. Overall, 192 patients were randomized to placebo, guselkumab 50 mg or 100 mg. At week 16, patients in the placebo group were crossed over to guselkumab 50 mg or 100 mg. At week 16, a significantly (P < 0.001) higher proportion of patients receiving guselkumab 50 mg and 100 mg versus placebo achieved IGA 0/1 (92.3% and 88.9% vs 7.8%) and PASI‐90 (70.8% and 69.8% vs 0%). Patients in guselkumab 50 mg and 100 mg groups achieved significant improvement versus placebo in PASI‐75 (89.2% and 84.1% vs 6.3%, P < 0.001) at week 16; improvement was maintained through week 52. Incidences of treatment‐emergent adverse events were comparable among the groups through week 16; the most commonly reported was nasopharyngitis. No new safety concerns were observed until week 52. In conclusion, guselkumab treatment demonstrated superior efficacy over placebo and was well tolerated in Japanese patients with moderate to severe plaque‐type psoriasis.     

Multiple NSAID intolerance in chronic idiopathic urticaria is correlated with delayed, pronounced and prolonged autoreactivity

Autologous serum skin test (ASST) reactivity is positive in up to 60% of patients with chronic idiopathic urticaria (CIU). About 21 to 30% of patients with CIU have intolerance to acetyl salicylic acid (ASA) and/or other chemically unrelated non-steroidal anti-inflammatory drugs (NSAIDs). To investigate the relationship between ASA/NSAID intolerance and ASST reactivity, a case-control study was performed in 110 patients with CIU and 60 healthy controls. A positive ASST was defined as an erythematous wheal with a diameter of > 5 mm more than the saline-induced response. Patients were assessed at 10-minute intervals for a minimum of three hours. ASA/NSAID intolerance was ascertained by a placebo controlled-provocation test with offending drug (s). Forty-two patients with CIU (38.2%) had autoreactivity whereas only two of the controls (3.3%) displayed early and weak skin responses (P<.0001). ASA/NSAID intolerance was demonstrated in 30 (27.3%) patients with CIU. The prevalences of autoreactivity were 93.3% (28/30) and 17.5% (14/80) in patients with and without ASA/NSAID intolerance, respectively (P<.001). Thirteen of the 25 ASST-positive patients (52%) who had single (n: 7) or multiple (n: 6) NSAID intolerance showed early (before or at 30 min) and mild autoreactivity of short duration, whereas 15 of the remaining 17 ASST-positive patients (88.2%) who all had multiple NSAID intolerance showed delayed (later than 30 min) and prolonged autoreactivity (P<.05). These findings suggest that a common mechanism may be responsible for the pathogeneses of both delayed autoreactivity and multiple NSAID intolerance in CIU. It might be further speculated that delayed, prolonged, and pronounced autoreactivity may be a possible predictor for multiple NSAID sensitivity in CIU.     

Efficacy and safety of secukinumab in Taiwanese patients with moderate to severe plaque psoriasis: Subanalysis from ERASURE phase III study

The efficacy and safety of secukinumab, a fully human anti‐interleukin‐17A monoclonal antibody, has been evaluated for moderate to severe plaque psoriasis in global trials which have included a low proportion of Asian subjects. We analyzed the efficacy and safety of secukinumab in Taiwanese patients in a phase III global clinical trial (ERASURE). Fifty‐one Taiwanese patients were randomized into s.c. placebo, 150 and 300 mg secukinumab treatment groups. The proportions of patients who achieved 75% or more improvement in Psoriasis Area and Severity Index (PASI‐75) at week 12 were 87.5% with 300 mg secukinumab, 70% with 150 mg secukinumab, 0% with placebo. Of the patients receiving 300 mg secukinumab, 68.8% achieved PASI‐90 at week 12. Analysis of overall patients receiving 300 mg secukinumab for 12 weeks showed that the proportion of PASI‐75 responders was less in patients with body mass index of 25 or more than less than 25. During the entire 52 weeks, the incidence of adverse events (AE) was consistent with the overall population in ERASURE. The most common AE (cases/per 100 patient‐year) during the entire treatment period were upper respiratory tract infection and pruritus. The duration of upper respiratory tract infection per 100 patient‐year was approximately 399 days in placebo, 1261 days in 150 mg secukinumab and 1805 days in 300 mg secukinumab. The safety and efficacy of secukinumab in Taiwanese patients was compatible with the global phase III study in the treatment of moderate to severe plaque psoriasis.     

Treatment of psoriasis with oral liarozole: a dose-ranging study

BACKGROUND: Liarozole is an inhibitor of the metabolism of all-trans-retinoic acid. Systemic administration increases tissue levels of this endogenous retinoid and has been reported to improve psoriasis in an open, uncontrolled study. OBJECTIVES: A multicentre, double-blind, placebo-controlled, dose-ranging study was therefore undertaken to determine the lowest effective oral dose of liarozole in the treatment of psoriasis vulgaris. PATIENTS/METHODS: Adult male and postmenopausal female patients requiring systemic treatment for psoriasis were randomized to receive placebo or liarozole at total daily doses of 50 mg, 75 mg or 150 mg for 12 weeks. The daily doses were each divided into two equal (morning and evening) doses. Response was assessed using an eight-point global scale to assess improvement and by monitoring the Psoriasis Area and Severity Index (PASI). The primary end-point was the proportion of subjects in each treatment group demonstrating 'marked improvement' or better as assessed on the eight-point scale. The tolerability of the treatment was assessed by recording mucocutaneous effects of retinoids and all adverse events. Biochemical and haematological monitoring were also performed. RESULTS: One hundred and thirty-nine subjects were randomized (118 male and 21 female) and 116 completed the study. A marked improvement or better response was observed in 6% of subjects on placebo, 18% on liarozole 50 mg, 11% on 75 mg and 38% on 150 mg. Only in the 150-mg group was the response rate significantly different to placebo (P < 0.001). Over the treatment period the mean PASI changed from 15.9 to 15.4 on placebo, from 17.4 to 13.8 on liarozole 50 mg, from 17.5 to 14.5 on 75 mg and from 15.8 to 8.8 on 150 mg. Again, only in the group receiving 150 mg was the response significantly better than placebo (P < 0.001). Liarozole was generally well tolerated. Mucocutaneous retinoid effects were generally infrequent and mild. Five subjects were withdrawn from treatment as a result of adverse events that may have been treatment related. These events were abnormalities of liver enzymes in two cases, an episode of erythema multiforme (in a patient receiving placebo), an allergic reaction in one and a rash accompanied by deterioration of the psoriasis in another. There was mild elevation of triglycerides in the groups receiving liarozole 75 mg and 150 mg daily. In males, the serum luteinizing hormone and testosterone levels rose significantly in all the active treatment groups. CONCLUSIONS: The data confirm that liarozole is an effective treatment for psoriasis and indicate that the lowest effective dose is 75 mg twice daily. The drug seems generally to be well tolerated.     

Long-term safety of isotretinoin as a treatment for acne vulgaris

We assessed possible long-term side-effects of isotretinoin therapy in 720 patients who had received one or more courses of treatment, and had a mean follow-up period of 4.9 years (range 2?12 years). Most patients (442) had received a total cumulative dose of 120?200 mg/kg body weight. One hundred and sixty-two patients received a cumulative dose of <120 mg/kg body weight, and 116 received a cumulative dose <200 mg/kg. Fifty-two patients (7.2%) reported persistent symptoms during the follow-up period. No correlation was found between age, sex, cumulative dose, or number of courses of isotretinoin and occurrence of reported possible side-effects. The reported symptoms were predominantly musculoskeletal (2%) or mucocutaneous (4.8%), and were mild in all cases. Xeroderma, dry eye syndrome, arthralgia, and possible exacerbation of eczema, were considered to be infrequent but probable long-term side-effects. The findings of this study indicate that isotretinoin in the treatment of acne is a safe drug, with no serious long-term side-effects.     

One‐year safety and efficacy study of bilastine treatment in Japanese patients with chronic spontaneous urticaria or pruritus associated with skin diseases

A number of second‐generation non‐sedating antihistamines are used in clinical practices over the world. However, long‐term safety and efficacy have not been proved high level evidence based medicine. We have performed an open‐label, multicenter, phase III study to evaluate the long‐term safety and efficacy of bilastine, a novel non‐sedating H₁‐antihistamine for patients with chronic spontaneous urticaria (CSU) or pruritus associated with skin diseases (trial registration no. JapicCTI‐142528). Patients aged 18–74 years were treated with bilastine 20 mg once daily for up to 52 weeks. Safety and tolerability were assessed on the basis of adverse events (AE), bilastine‐related AE, laboratory tests and vital signs. Efficacy was assessed based on rash score, itch score, overall improvement and quality of life. One hundred and ninety‐eight patients enrolled, 122 of whom (61.6%) completed the 52‐week treatment period. AE were reported in 64.5% and bilastine‐related AE in 2.5% of patients throughout the 52‐week treatment period. All AE were mild to moderate in severity. AE associated with the nervous system occurred in 10 patients (5.1%) including seven patients (3.6%) with headache. Somnolence reported in two of these patients (1.0%) was related to bilastine. All efficacy variables improved during treatment with bilastine. In conclusion, long‐term treatment with bilastine 20 mg once daily for 52 weeks is safe and well tolerated in Japanese patients with CSU or pruritus associated with skin diseases. Bilastine improved disease symptoms of both conditions early in treatment, and the efficacy was maintained throughout the treatment.     

Safety and efficacy of nivolumab in Japanese patients with malignant melanoma: An interim analysis of a postmarketing surveillance

A postmarketing surveillance study is ongoing to evaluate nivolumab treatment for Japanese patients with malignant melanoma and accumulate data on all adverse events (AE) and efficacy. In this interim analysis, we evaluated data from approximately 100 Japanese medical institutions obtained from the nivolumab approval date in Japan (4 July 2014) through 3 July 2016. Patients were monitored during the first 12 months of treatment. Nivolumab was administrated by i.v. infusion (2 mg/kg every 3 weeks). A total of 680 and 610 patients were evaluated for safety and efficacy, respectively. The incidences of adverse drug reactions (ADR) and grade 3 or higher ADR were 53.53% and 12.35%, respectively. Predominant ADR included hypothyroidism (11.32%) and abnormal enzyme activity, such as increase of aspartate aminotransferase (7.79%), alanine aminotransferase (6.76%), alkaline phosphatase (6.18%) and γ‐glutamyltransferase (5.44%). Grade 3 or higher ADR of special interest with an incidence of 1% or higher were hepatic function disorder (2.50%), colitis/diarrhea (2.06%) and infusion reaction (1.32%). No cases of encephalitis or venous thromboembolism, other AE of special interest, were observed. The estimated median overall survival was 379 days (95% confidence interval [CI], 290–not reached [NR]) in the overall population, NR (95% CI, 305–NR) for cutaneous melanoma and 340 days (95% CI, 275–NR) for mucosal melanoma. The improvement rate based on the antitumor response at the last evaluation was 22.2% (131/590 patients). No new safety concerns were raised, and serious ADR of special interest were infrequent. Nivolumab showed equivalent efficacy in patients with mucosal melanoma and those with cutaneous melanoma.     

Oral hyposensitization to poison ivy and poison oak

We evaluated the safety and efficacy of a 1:1 mixture of pentadecylcatechol (PDC) and heptadecylcatechol (HDC) diacetate in reducing hypersensitivity to poison ivy and poison oak. The study was double-blind, parallel, randomized, and placebo controlled. The 44 subjects receiving the active drug ingested a cumulative dose of 306.5 mg over a five-week period. Subsequently, 14 patients were continued on a maintenance phase, ingesting an additional 960 mg of drug. The PDC-HDC diacetate was well tolerated, with no significant side effects. Evaluation of efficacy compared poststudy and prestudy reactions to patch tests using urushiol in doses of 0.025, 0.05, 0.125, 0.25, and 0.5 micrograms applied to the forearm. The results indicated that the induction phase as well as the maintenance phase did not induce a statistically significant hyposensitivity to urushiol, and we were thus unable to decrease sensitivity to poison ivy and poison oak in humans using orally ingested PDC-HDC diacetate.     

Alefacept

black triangle Alefacept (recombinant human LFA-3/IgG(1) fusion protein) is a novel biologic agent that selectively targets memory-effector CD45RO+ T lymphocytes, implicated in psoriasis pathogenesis. black triangle In placebo-controlled studies, once-weekly administration of alefacept 7.5mg intravenous (IV) and 15mg intramuscular (IM) for 12 weeks significantly improved psoriasis and produced durable clinical improvements in patients with moderate-to-severe chronic plaque psoriasis who responded. black triangle At any time during the first 12-week course of alefacept (followed by 12 weeks' treatment-free follow-up), approximately 30% of patients achieved the primary endpoint of a > or =75% improvement in psoriasis, while approximately 55% achieved a > or =50% improvement; the corresponding results during a second course were approximately 40% and 70%, respectively. black triangle Alefacept therapy significantly improved quality of life in responders, who reported improved perception of overall health, increased energy levels, and enhanced emotional well-being. black triangle One or two 12-week courses of IV alefacept 7.5 mg/week and IM alefacept 15 mg/week were similarly well tolerated, with a safety/tolerability profile similar to placebo. No organ-based toxicity or disease rebound after alefacept withdrawal has been reported. black triangle Alefacept exhibits a low potential for immunogenicity and has no clinical effects indicative of generalized immunosuppression. No opportunistic infections have been reported, nor is there evidence of an increased risk of malignancies.     

Evaluation of the effect of the specific CCR1 antagonist CP-481715 on the clinical and cellular responses observed following epicutaneous nickel challenge in human subjects

Background: The CC‐chemokine receptor‐1 (CCR1) is thought to be involved in recruitment of inflammatory cells in allergic contact dermatitis (ACD). CP‐481715 is a specific antagonist of CCR1. Objectives: To determine the inhibitory effects of CP‐418 715 in ACD by evaluating the clinical signs and cellular infiltration in skin biopsies following epicutaneous nickel challenge in allergic subjects. Subjects/Methods: In this phase 1/2 study, 40 subjects were randomized to 5 days of treatment in four parallel groups (placebo three times daily (TID), placebo once daily (QD), 1000 mg CP‐418 715 TID, and 3000 mg CP‐418 715 QD). Twenty‐four hours after the first drug administration, nickel sulfate patches were applied on subjects’ backs and removed 48 hours later. Results: Pretreatment with 1000 mg CP‐481715 TID resulted in significant reductions in visual scores of the nickel reactions (P = 0.01). Instrumentally measured erythema tended to decrease in the CP‐481715 mg TID group (P = 0.06). No differences were noted between the 3000 mg CP‐481715 mg QD group and pooled placebo. No significant differences were found for immunohistological cell counts. CP‐418 715 was generally safe and well tolerated. Conclusions: Blocking of CCR1 only partly inhibited clinical manifestations of ACD. Several chemokine receptors are likely relevant for the cellular influx observed in ACD lesions.     

A randomized,double-blind,placebo-controlled phase III study evaluating efficacy and tolerability of 2 courses of alefacept in patients with chronic plaque psoriasis

BACKGROUND: In previous phase II studies, alefacept significantly improved psoriasis and was well tolerated. The clinical response to alefacept was durable. OBJECTIVE: Our purpose was to further evaluate efficacy and tolerability of alefacept in a phase III study of patients (n = 553) with chronic plaque psoriasis. METHODS: Two 12-week courses of once-weekly intravenous alefacept 7.5 mg or placebo were given in a randomized double-blind study; patients were followed up for 12 weeks after each course. RESULTS: During treatment and follow-up of course 1, a 75% or greater reduction in the Psoriasis Area Severity Index (PASI) was achieved by 28% of alefacept-treated and 8% of placebo-treated patients (P <.001). Patients who received a single course of alefacept and achieved a 75% or greater reduction from baseline PASI during or after treatment, without the use of phototherapy or systemic therapies, maintained a 50% or greater reduction in PASI for a median duration of more than 7 months. Among patients who received 2 courses of alefacept, 40% and 71% of patients achieved a 75% or greater and 50% or greater reduction in PASI, respectively, during the study period. Alefacept was well tolerated over both courses. In course 1, the incidence of transient chills was higher in the alefacept group compared with the placebo group; more than 90% of cases occurred within 24 hours after the first few doses. CONCLUSION: Alefacept significantly improved psoriasis and produced durable clinical improvements among patients who responded. A second course of alefacept increased efficacy and was equally well tolerated.     

Stevens-Johnson综合征及中毒性表皮坏死松解症61例回顾性分析

目的 探讨Stevens-Johnson综合征（SJS） 及中毒性表皮坏死松解症（TEN）患者的病因及治疗经验。方法 回顾性分析1994年7月至2007年5月确诊为SJS和TEN的61例患者的临床资料,根据治疗分为静脉滴注免疫球蛋白联合糖皮质激素组（简称IVIG组）16例及糖皮质激素组（简称激素组）45例,采用SCORTEN评分评价病情严重程度及预后。比较激素初始量、最大控制量、减量前激素总量、IVIG总量、激素减量前时间、住院时间等指标。结果 引起SJS和TEN常见致敏药物依次为非甾体抗炎药类（26例）、抗癫痫药（15例）、抗生素类（10例）,其中最多的为卡马西平（13例）。IVIG组SCORTEN评分（1.44 ± 1.21）显著高于激素组（0.80 ± 1.10）,两组差异有统计学意义（P < 0.05）。IVIG组减量前激素总量、减量前时间及住院治疗时间（分别为12.06 ± 4.32 mg/kg,7.81 ± 2.29 d,18.00 ± 5.92 d）与激素组（分别为12.52 ± 8.29 mg/kg,8.29 ± 4.18 d,21.07 ± 13.36 d）比较,差异均无统计学意义。11例SCORTEN评分等于2的患者联用IVIG及激素能使住院治疗时间从（27.57 ± 9.90） d缩短至（14.50 ± 2.38） d（P < 0.05）。IVIG组并发症发生率（43.8％）高于激素组（24.4％）（P < 0.05）。IVIG组与激素组实际死亡率分别为12.5％及4.4％,均低于预期死亡率（分别为12.9％及7.9％）。结论 激素及IVIG治疗SJS和TEN有效。     

Topical diclofenac in hyaluronan gel for the treatment of solar keratoses

This randomized, double-blind, placebo-controlled study assessed the efficacy and safety of a topical gel containing 3% diclofenac in 2.5% hyaluronan in 150 patients with solar keratoses (SK). The active treatment was compared with the vehicle only, hyaluronan gel, as placebo over a 12-week period. Patients in both groups applied the active treatment or placebo to a targeted area of skin (0.25 g b.d.). At 12 weeks the mean lesion-count reduction in the targeted area was not significantly different between treatments. However, at post-termination follow up (16 weeks), there was a highly significant decrease in the number of lesions, 6.2 +/- 7.5 standard deviations (SD) (56.1% reduction) in the active treatment group compared with 2.4 +/- 4.3 SD (23.6% reduction) in the placebo group (P < 0.001). Other efficacy measures (complete lesion resolution, >50% lesion reduction) were also significantly different (P < 0.01) between treatments at 16 weeks. In conclusion, topical 3% diclofenac in 2.5% hyaluronan gel was effective and well tolerated in this study, suggesting a role for this therapy in the treatment of SK.