Apremilast was effective in moderate to severe plaque psoriasis.

No abstract

BackgroundApremilast, an oral, small‐molecule phosphodiesterase 4 inhibitor, has demonstrated efficacy in patients with moderate‐to‐severe psoriasis.ObjectiveEvaluate efficacy and safety of apremilast vs. placebo in biologic‐naive patients with moderate‐to‐severe plaque psoriasis and safety of switching from etanercept to apremilast in a phase IIIb, randomized, double‐blind, placebo‐controlled study (NCT01690299).MethodsTwo hundred and fifty patients were randomized to placebo (n = 84), apremilast 30 mg BID (n = 83) or etanercept 50 mg QW (n = 83) through Week 16; thereafter, all patients continued or switched to apremilast through Week 104. The primary efficacy endpoint was achievement of PASI‐75 at Week 16 with apremilast vs. placebo. Secondary endpoints included achievement of PASI‐75 at Week 16 with etanercept vs. placebo and improvements in other clinical endpoints vs. placebo at Week 16. Outcomes were assessed through Week 52. This study was not designed for apremilast vs. etanercept comparisons.ResultsAt Week 16, PASI‐75 achievement was greater with apremilast (39.8%) vs. placebo (11.9%; P < 0.0001); 48.2% of patients achieved PASI‐75 with etanercept (P < 0.0001 vs. placebo). PASI‐75 response was maintained in 47.3% (apremilast/apremilast), 49.4% (etanercept/apremilast) and 47.9% (placebo/apremilast) of patients at Week 52. Most common adverse events (≥5%) with apremilast, including nausea, diarrhoea, upper respiratory tract infection, nasopharyngitis, tension headache and headache, were mild or moderate in severity; diarrhoea and nausea generally resolved in the first month. No new safety or tolerability issues were observed through Week 52 with apremilast.ConclusionApremilast demonstrated significant efficacy vs. placebo at Week 16 in biologic‐naive patients with psoriasis, which was sustained over 52 weeks, and demonstrated safety consistent with the known safety profile of apremilast. Switching from etanercept to apremilast did not result in any new or clinically significant safety findings, and efficacy was maintained with apremilast through Week 52.

Apremilast demonstrated an acceptable safety profile and was generally well tolerated for ≥156 weeks.

Polychlorinated naphthalene (PCN) and polychlorinated biphenyl (PCB) congeners were measured in whole body and fillet of fishes collected from Michigan waters, including the Great Lakes, during 1996−1997. PCNs were found in all the fishes analyzed including those from Siskiwit Lake, a remote lake located near the southern shoreline of Isle Royale National Park in Lake Superior. Concentrations of total PCNs in fishes ranged from 19 to 31 400 pg/g, wet wt, and varied depending on sampling location and species. Fishes from the Detroit River contained the greatest concentrations of both PCNs and PCBs. Concentrations of total PCNs in fishes from Michigan waters were significantly correlated with the concentrations of PCBs. As with total PCN concentrations, the profiles of PCN isomer/congener distribution in fishes varied among sampling locations and species. Fishes from the Detroit River contained PCN profile similar to that of Halowax 1014, whereas those from Siskiwit Lake and Lake Superior contained greater proportions of congeners which have great bioaccumulative potential. Estimated concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TEQs) of PCNs ranged from 0.007 to 11 pg/g, wet wt. PCN congeners 66/67 and 69 accounted for greater than 80% of the TEQs contributed by PCNs. TEQs contributed by PCBs, estimated based on H4IIE bioassay-derived TEFs, were in the range of 0.06−11 pg/g, wet wt, which were similar to those contributed by PCNs. When international TEFs (I-TEFs) for coplanar PCBs were applied, estimated PCB-TEQs ranged from 0.46 to 79 pg/g, wet wt, which were 5−10 times greater than those that were estimated from H4IIE TEFs. PCB congener 126 contributed greater than 50% of the TEQs contributed by PCBs in all the fishes. Overall, when similarly derived TEFs were used, PCNs contributed 2−57% of the sum of TEQs of PCNs and PCBs.