Efficacy and safety of piclidenoson in plaque psoriasis: Results from a randomized phase 3 clinical trial (COMFORT-1).

OBJECTIVE: A3 adenosine receptor (A3AR) is overexpressed in the skin and peripheral blood mononuclear cells of psoriasis patients. We investigated the efficacy/safety of piclidenoson (CF101), an orally bioavailable A3AR agonist that inhibits IL-17 and IL-23 production in keratinocytes, in moderate-to-severe plaque psoriasis. METHODS: The randomized, placebo- and active-controlled, double-blind phase 3 COMFORT-1 trial randomized patients (3:3:3:2) to piclidenoson 2 mg BID, piclidenoson 3 mg BID, apremilast 30 mg BID or placebo. At Week 16, patients in the placebo arm were re-randomized (1:1:1) to piclidenoson 2 mg BID, piclidenoson 3 mg BID or apremilast 30 mg BID. The primary end point was the proportion of patients achieving ≥75% improvement in Psoriasis Area and Severity Index (PASI) from baseline (PASI-75) at Week 16 versus placebo. RESULTS: A total of 529 patients were randomized and received ≥1 dose of study medication (safety population). The efficacy analysis population for the primary end point included 426 patients (piclidenoson 2 mg BID, 127; piclidenoson 3 mg BID, 103; apremilast, 118; placebo, 78). Piclidenoson at 2 and 3 mg BID exhibited similar efficacy. The primary end point was met with the 3 mg BID dose: PASI 75 rate of 9.7% versus 2.6% for piclidenoson versus placebo, p = 0.037. The PASI responses with piclidenoson continued to increase throughout the study period in a linear manner. At week 32, analysis in the per-protocol population showed that a greater proportion of patients in the piclidenoson 3 mg BID arm (51/88, 58.0%) achieved improvement from baseline in Psoriasis Disability Index (PDI) compared to apremilast (59/108, 55.1%), and the test for noninferiority trended towards significance (p = 0.072). The safety/tolerability profile of piclidenoson was excellent and superior to apremilast. CONCLUSIONS: Piclidenoson demonstrated efficacy responses that increased over time alongside a favourable safety profile. These findings support its continued clinical development as a psoriasis treatment (ClinicalTrials.gov identifier: NCT03168256).

[Morphology of nystagmus in childhood]. / Nystagmusmorphologie im Kindesalter.

Taking 100 patients with nystagmus--aged between 4 and 12--seen by the authors, the numerous different waveforms and wave types were classified on the basis of the electronystagmograms. The most common forms of nystagmus were the pseudopendular, the pseudocycloid, and the pendular. Over 25 percent of the nystagmograms were cases of latent nystagmus and were therefore excluded from the waveform analysis. The average visual acuities for the various nystagmus waveforms are compared.

[Diagnosis and treatment of Stilling-Türk-Duane syndrome (clinical electromyographic and electrooculographic studies)]. / Zur Diagnostik und Behandlung des Stilling-Türk-Duane-Syndroms (klinische, elektromyographische und elektrookulographische Untersuchungen).

The results of clinical, EMG and EOG examinations in 42 patients with Duane's syndrome are analyzed and some characteristic clinical examples are presented. The clinical analysis of motoric and sensoric disturbances in Duane's syndrome reveals elements of concomitant squint in ocular statics. Dynamically, there are marked differences with regard to concomitant and paralytic squint. A number of interesting observations are reported relating to the permanent tonic innervation of the lateral rectus muscle, polymorphic EOG dyssynergia in saccadic and smooth pursuit movements and the progression of the clinical picture in some patients with Duane's syndrome. Twenty patients were surgically treated with relatively good results or at least some improvement.

[Electronystagmographic evaluation of surgical results in nystagmus treatment]. / Elektronystagmo-graphische Beurteilung der operativen Ergebnisse in der Nystagmusbehandlung.

In the management of congenital, ocular nystagmus as well surgical procedures (according Kestenbaum, Anderson and similar modifications) with the purpose of shifting nystagmus "neutral zone" in the primary position of gaze, as nonsurgical treatment with prisms, show favourable effect on head position, nystagmus intensity and visual acuity. In this preliminary report the authors tried to evaluate, by means of electronystagmography, their clinical experiences in some treated nystagmus cases, objectively. The electronystagmographic findings of nystagmus amplitude, frequency and intensity, depending on position of gaze, were before and after surgery, respectively treatment analysed.

[Chronic progressive external ophthalmoplegia with atypical retinal pigment dystrophy (author's transl)]. / Ophthalmoplegia externa chronica progressiva mit atypischer Netzhautpigmentdystrophie.

A brief review of the literature on chronic progressive external ophthalmoplegia is followed by a description of two unusual cases. The first, Kearns-Shy syndrome, was a pronounced case of "ophthalmoplegia-plus syndrome", though with normal retinal function. The second patient had retinal pigment dystrophy with severe disturbance of retinal function, as well as a complete lack of ocular motility.

[Electrooculographic examination in paralytic and concomitant squint (author's transl)]. / Elektrookulographische Untersuchungen beim Lähmungsund Begleitschielen.

There are shown some possibilities of electrooculographic diagnostics in different forms of strabismus. Kinetic disturbances in fusion in concomitant squint are usually frequent but not constant and in the majority they are different from incomitances in paralytic squint. In this mind electrooculography represents subtile and perspective method in examination of ocular motility.

[Histological examination of resected eye muscles in concomitant squint (author's transl)]. / Histologische Untersuchungen von resezierten Augenmuskeln beim Begleitschielen

The changes of muscle tissue are found as well in convergent as in divergent squint, especially in insufficiency of convergence. The histological changes are more pronounced in monocular strabism but they can also be found in alternating squint. They are observed in early occuring strabismus, but especially frequently in patients with a large angle of squint, in cases of severe amblyopia and defective binocular vision. The errors of refraction make no influence. All histological changes, described in this paper, have been already found in eye muscles of little children.

[Electromyographic examinations in exo-deviations (author's transl)]. / Elektromyographische Untersuchungen bei Exodeviationen

On the basis of EMG-examinations in various forms of exo-deviation as classified by Burian, the authors conclude, that these show also various innervation disturbances, and that also histological differences can be proved. The practical sense of these observations would be in narrowing the indications for exotropia operations.