Secukinumab provides sustained PASDAS-defined remission in psoriatic arthritis and improves health-related quality of life in patients achieving remission: 2-year results from the phase III FUTURE 2 study

Background

Secukinumab has demonstrated sustained improvement in the signs and symptoms of psoriatic arthritis (PsA) over 2?years in the FUTURE 2 study (NCT01752634). This post hoc analysis assessed the ability of secukinumab to achieve Psoriatic Arthritis Disease Activity Score (PASDAS)-based remission or low disease activity (LDA) through 2?years among patients with PsA in the FUTURE 2 study.

Methods

PASDAS (cut-off scores: remission ≤?1.9; LDA >?1.9 and?<?3.2; Moderate Disease Activity ≥?3.2 and?<?5.4; and high disease activity [HDA]?≥?5.4) was assessed in the overall population (tumour necrosis factor inhibitor [TNFi]-naïve and TNFi-experienced), in patients stratified by prior TNFi use and by disease duration at weeks 16, 52 and 104. The impact of secukinumab on individual PASDAS core components and on the relationship between PASDAS states and patient-reported outcomes (PROs), including physical function, health-related quality of life (HRQoL) and work productivity, were also assessed. Data for the approved doses of secukinumab (300 and 150?mg) are reported. PASDAS scores and core components were reported as observed, and PROs were analysed using mixed models for repeated measures.

Results

In the overall population, PASDAS remission and LDA were achieved in 15.6% and 22.9%, respectively, of patients treated with secukinumab 300?mg and in 15.2% and 19.2%, respectively, in the secukinumab 150?mg group versus 2.3% and 13.8%, respectively, with placebo at week 16. In the TNFi-naïve group, a higher proportion of patients achieved remission?+?LDA at week 16 with secukinumab 300 and 150?mg (46.2% and 42.9%, respectively) versus placebo (17.5%), with corresponding responses in TNFi-experienced patients being 22.6% and 19.4% versus 13.3%. Remission/LDA responses with secukinumab were sustained through 2?years. Patients achieving remission/LDA reported greater improvements in PROs than patients in HDA through 2?years.

Conclusions

Secukinumab-treated patients achieved higher PASDAS-defined remissions or LDA compared with placebo at week 16, which were sustained through 2?years. Remission/LDA was achieved by both TNFi-naïve and TNFi-experienced patients treated with secukinumab, with higher rates in TNFi-naïve patients. Secukinumab-treated patients achieving remission/LDA reported significantly greater improvements in PROs, including physical function and different dimensions of health-related quality of life and work, than patients in HDA.

Trial registration

ClinicalTrials.gov, NCT01752634. Registered on December 19, 2012.EUDRACT, 2012-004439-22. Registered on December 12, 2012.

     

Interplasmid transposition of the mariner transposable element in non-drosophilid insects

Plasmid-based transposition assays were performed in developing embryos of the Australian sheep blowfly Lucilia cuprina and the Queensland fruit fly Bactrocera tryoni, using the mariner transposable element from Drosophila mauritiana. Transposition products were recovered that were identical in structure to those recovered from D. melanogaster. Only sequences delimited by the mariner terminal repeats were transposed and all insertions occurred at TA residues, and duplicated these. These are the hallmarks of mariner transpositions observed in the chromosomes of D. melanogaster and D. mauritiana, indicating that the plasmid-based assays are accurate indicators of mariner transposition activity. The recovery of precise transposition products from L. cuprina and B. tryoni demonstrates that mariner should be capable of producing germline transformants in these species. The results obtained from these assays suggests that they will be extremely useful in determining if mariner can transpose in other non-drosophilid insects and for investigating factors that might affect mariner transposition frequency.     

The effect of concentrated smoke products on the restoration of highly disturbed mineral sands in southeast Victoria

Summary Recent studies have recognized the potential of broad‐scale surface application of smoke compounds for enhancing germination from the soil seed‐bank in fire‐prone vegetation communities. Results suggest that smoke technology may play, in the future, a significant role in the restoration and management of areas supporting indigenous vegetation. An important step in the development of smoke‐based restoration tools is the conduct of in situ field trials in a range of geographical locations and environmental conditions. However, most of the published work on the effectiveness of smoke products in promoting seedbank germination has been conducted at sites in southwestern Australia. The present study examines the effect of commercially available smoke‐water products on the regeneration of a highly disturbed former mine‐site at the Royal Botanic Gardens Cranbourne, in southeastern Victoria. Various combinations of concentrated smoke products and topsoil harvested from a nearby heathy woodland community were applied to exposed, uniform mineral sands to test their effect on seedling density and species richness of regrowth. The trials showed that after 12 months a number of common, herbaceous species including Austrodanthonia setacea, Opercularia varia and Platysace heterophylla were recorded in significantly higher numbers in areas treated with a commercial smoke‐water. However, there was no overall improvement in the density of seedlings or the richness of species as a result of the application of the smoke products. Similarly, total seedling density and species richness were not affected by the addition of topsoil, either alone or in combination with smoke products.     

Anaerobic Degradation of Benzene, Toluene, Ethylbenzene, and Xylene Compounds by Dechloromonas Strain RCB

Dechloromonas strain RCB has been shown to be capable of anaerobic degradation of benzene coupled to nitrate reduction. As a continuation of these studies, the metabolic versatility and hydrocarbon biodegradative capability of this organism were investigated. The results of these revealed that in addition to nitrate, strain RCB could alternatively degrade benzene both aerobically and anaerobically with perchlorate or chlorate [(per)chlorate] as a suitable electron acceptor. Furthermore, with nitrate as the electron acceptor, strain RCB could also utilize toluene, ethylbenzene, and all three isomers of xylene (ortho-, meta-, and para-) as electron donors. While toluene and ethylbenzene were completely mineralized to CO₂, strain RCB did not completely mineralize para-xylene but rather transformed it to some as-yet-unidentified metabolite. Interestingly, with nitrate as the electron acceptor, strain RCB degraded benzene and toluene concurrently when the hydrocarbons were added as a mixture and almost 92 μM total hydrocarbons were oxidized within 15 days. The results of these studies emphasize the unique metabolic versatility of this organism, highlighting its potential applicability to bioremediative technologies.     

The Role of Clostridium perfringens in the Growth Response of Chicks to Dietary Penicillin

S ummary . The previous observation that Clostridium perfringens is responsible for penicillin-relieved growth depression in chicks has been reassessed. The administration of Cl. perfringens to germfree chicks, to birds harbouring a non-growth depressing gut flora and to birds reared in an environment free from Cl. perfringens was without effect on growth rate. No correlation was observed in conventional chicks between the incidence of growth depression and the presence of Cl. perfringens in the gut of the chicks one day after food was first given.     

Immune protection against experimental autoimmune encephalomyelitis: optimal conditions and analysis of mechanism

Protection against experimental autoimmune encephalomyelitis (EAE) was studied in the guinea pig and the Lewis rat. Basic protein of myelin (BPM) injected in incomplete Freund's adjuvant (IFA) gave solid protection against subsequent challenge with normally encephalitogenic doses of BPM in complete Freund's adjuvant (CFA). Protection depended on the amount of BPM in IFA injected and on the duration of the interval between protection and encephalitogenic challenge with BPM in CFA. Notably, protection was long lasting; it remained demonstrable, to some degree for 52 weeks in guinea pig and 32 weeks in rats, these being the longest intervals tested.Protection could not be correlated with serum antibody levels to BPM, and was afforded in the guinea pig by the injection, in IFA, of a synthetic peptide matching residues 112–122 of human BPM; this peptide produced no detectable serum antibody to BPM. Protected guinea pigs had intact cell-mediated immunity to BPM, as measured by inhibition of macrophage migration in vitro. The mechanism of protection may involve the production, following injection of BPM in IFA, of a class of suppressor thymic lymphocytes capable of overriding otherwise encephalitogenic thymic lymphocytes.     

Measurement of the rate of stomach emptying using Indium-113m and a 10-crystal rectilinear scanner

Accurate reproducible measurements of the rate of gastric emptying have only been possible since the advent of external radionuclide detection techniques. Indium-113m and a 10-crystal rectilinear scanner have been employed to measure stomach emptying rates. The technique is simple, the results reproducible and it has proved ideal for assessing the results of drug therapy in patients with gastric retention. In the normal individual the T50% was 42 to 95 minutes, and the relationship between counts and time was, to first approximation, a linear function.