Tofacitinib in patients with moderate-to-severe chronic plaque psoriasis: long-term safety and efficacy in an open-label extension study.

BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor. Final safety and efficacy data from an open-label extension study of tofacitinib in psoriasis are reported. OBJECTIVES: To evaluate the long-term safety and durability of efficacy of tofacitinib in adults with moderate-to-severe chronic plaque psoriasis. METHODS: Eligible patients who completed qualifying phase II/III tofacitinib studies received tofacitinib 10 mg twice daily (q12h) until month 3; subsequently, the dose could be adjusted by investigators to either 5 or 10 mg q12h. Adverse events (AEs) are reported up to month 66 and laboratory data up to month 54. Efficacy end points up to month 54 included Physician's Global Assessment of 'clear' or 'almost clear' (PGA response) and 75% improvement in Psoriasis Area and Severity Index (PASI 75). RESULTS: Overall, 2867 patients received tofacitinib, with a median treatment duration of 35·6 months. Adverse events (AEs) and serious AEs were reported in 82·5% and 13·7% of patients, respectively; 13·9% of patients discontinued owing to AEs; and 29 patients died. Incidence rates (patients with event/100 patient-years) were 1·16 for serious infections, 0·67 for malignancies and 0·26 for major adverse cardiovascular events. After initial changes in qualifying studies, most laboratory parameters were generally stable over 54 months. PGA response was achieved by 52-62% of patients and PASI 75 by 56-74% of patients at each study visit through month 54. CONCLUSIONS: In patients with psoriasis, the safety profile of tofacitinib over 66 months was similar to previous reports in phase III studies and efficacy was sustained through 54 months (NCT01163253).

Making the most of Papua New Guinea's biodiversity: Establishment of an integrated set of programs that link botanical survey with pharmacological assessment in "The Land of the Unexpected"

An integrated and coordinated set of programs has been established to meet ICBG goals in Papua New Guinea (PNG). Here we give an overview of the PNG ICBG and focus on the key elements and major steps taken to establish a program necessary for the pharmacological assessment of botanicals and traditional medicines in PNG and, by extrapolation, in other developing countries.

3,7-Dimethylguanine, a new purine from a Philippine sponge Zyzzya fuliginosa.

A new purine 3,7-dimethylguanine (1) has been isolated from the marine sponge Zyzzya fuliginosa, along with the known metabolites, makaluvamines A, C, K (2--4), 4-hydroxyphenylacetic acid (5), methyl ester of 4-hydroxyphenylacetic acid (6), 4-hydroxyphenethyl alcohol (7), L-phenylalanine (8) and L-tryptophan (9). The structure of 3,7-dimethylguanine (1) was elucidated by analysis of 1D and 2D (one- and two-dimensional) NMR [HMQC (heteronuclear multiple quantum coherence), gHMBC (heteronuclear multiple bond connectivity), 1H-15N gHMBC] data, mass spectroscopy data, and by comparison with 3,7-dimethylisoguanine (10).

New cyclic peroxides from the Philippine sponge Plakinastrella sp.

Three new cyclic peroxides 5-7 and a new carboxylic acid ester 8 were isolated as minor metabolites from the hexane extract of a Plakinastrella species from the Philippines. The structures of compounds 5-8 were elucidated by interpretation of spectral data and by chemical interconversion, and the absolute stereochemistry of peroxide 6 was determined by application of Mosher's method to a derivative. Although the major compounds in the sponge showed activity against Candida albicans prior to decomposition, the minor metabolites 5-8 are essentially inactive.

Luffasterols A-C, 9,11-secosterols from the Palauan sponge Luffariella sp.

The Palauan sponge Luffariella sp. contained manoalide (6) and secomanoalide (7) as the major metabolites. The minor metabolites, luffasterols A-C (3-5) are 9,11-secosterols that contain a 3 beta-acetoxy-5 alpha,6 alpha-epoxy-9-oxo-9,11-secocholest-7-en-11-al ring system joined to three different side chains. The structures of the luffasterols were elucidated by interpretation of spectroscopic data.

Makaluvamines H-M and damirone C from the pohnpeian sponge Zyzzya fuliginosa.

Seven new pyrroloiminoquinone alkaloids, makaluvamines H-M [19-24] and damirone C[25], together with the known compounds, makaluvamines C[13], D[14], and G[17], were isolated from the sponge Zyzzya fuliginosa collected at Nahpali Island, Pohnpei, Micronesia. The structures of the new compounds were elucidated by interpretation of spectral data. The chemotaxonomic relationships involving the makaluvamines and related pyrroloiminoquinone alkaloids are discussed.

Oceanapamine, a sesquiterpene alkaloid from the Philippine sponge Oceanapia sp.

The major metabolite of the Philippine sponge Oceanapia sp. is the antimicrobial alkaloid oceanapamine [1], which was isolated as a trifluoroacetate salt. The structure and the absolute configuration of oceanapamine, which consists of a monocyclic sesquiterpene attached to a histamine residue, were elucidated by interpretation of spectroscopic data.

Unstable enol sulfates from a two-sponge association.

An inseparable two-sponge association, consisting of a Haliclona sp. and a choristid sponge, yielded two unstable enol sulfates, (1E)-2- (3',4'-dihydroxyphenyl)ethylene sulfate [3] and (1Z)-2-(3',4'-dihydroxyphenyl)ethylene sulfate [4]. Methanolysis converted the enol sulfates into 2-(3',4'-dihydroxyphenyl)-1,1,2-trimethoxyethane [5] by an oxidative mechanism.