Conjunctivitis in dupilumab clinical trials

Background Dupilumab blocks the shared receptor component for interleukin (IL)-4 and IL-13. It is approved in the U.S.A. for patients aged ≥ 12 years with moderate-tosevere atopic dermatitis (AD) uncontrolled by topical prescription medicines or who cannot use topical medicines, for patients in Japan whose AD is uncontrolled with existing therapies, for patients with moderate-to-severe AD in Europe who are candidates for systemic therapy and for patients aged ≥ 12 years for maintenance treatment of moderate-to-severe asthma uncontrolled with their current medicines. AD trials have reported increased incidence of conjunctivitis for dupilumab vs. placebo. Objectives To characterize further the occurrence and risk factors of conjunctivitis in dupilumab clinical trials. Methods We evaluated randomized placebo-controlled trials of dupilumab in AD (n = 2629), asthma (n = 2876), chronic rhinosinusitis with nasal polyps (CRSwNP) (n = 60) and eosinophilic oesophagitis (EoE) (n = 47). Results In most AD trials, dupilumab-treated patients had higher conjunctivitis incidence than placebo controls. Higher baseline AD severity and previous history of conjunctivitis were associated with increased conjunctivitis incidence. Conjunctivitis was mostly mild to moderate. Most cases recovered or resolved during the treatment period; two patients permanently discontinued dupilumab due to conjunctivitis or keratitis. Common treatments included ophthalmic corticosteroids, antibiotics, and antihistamines or mast cell stabilizers. Most cases were diagnosed by the investigators. In asthma and CRSwNP trials, the incidence of conjunctivitis was lower for both dupilumab and placebo than in AD trials; dupilumab did not increase the incidence compared with placebo. In the EoE trial, no patients had conjunctivitis. Conclusions Conjunctivitis was more frequent with dupilumab treatment in most AD trials. In dupilumab trials in other type 2 diseases, incidence of conjunctivitis was overall very low, and was similar for dupilumab and placebo. In AD, the incidence of conjunctivitis was associated with AD severity and prior history of conjunctivitis. The aetiology and treatment of conjunctivitis in dupilumab-treated patients require further study

Lenin (1870-1924), Stalin (1878-1953), and nationalism

Lenin and Stalin did not accept the classical nationalist view of the nation-state as the most desirable form of state, but they recognized the nation as a significant political, economic, and cultural reality. The Soviet Union was organized as a federation of nations. Though the individual republics received some real power, the Moscow center monopolized the most important decisions. Both men acknowledged the right of Soviet nations to their own languages, cultures, and cadres, and Stalin developed articulate policies around this principle after Lenin's death. But national development became ever more restricted by Soviet state patriotism and russocentrism, leading to mass murder, ethnic cleansing, and xenophobic anticosmopolitanism. Though the Soviets established their hegemony after the war, the Eastern European states were not annexed to the USSR. The Communist International accepted the revolutionary potential of nationalism in the colonial world. Stalin gave a prominent role to the patriotic factor in international communist policies

Clinical Photography and Noninvasive Optics

Over the years, digital photography has proven to be a useful and in some respects indispensable technology in supporting the clinical activity of the doctor. In association with epiluminescence investigation, it makes a major contribution to the archiving and localization of pigmented lesions, in order to verify the progression of each lesion present on the patient’s skin over time. New noninvasive diagnostic systems exploit a three-dimensional (3D) optical measurement system that is able to offer the operator an appropriate device for storing, analyzing, reproducing, and processing data obtained from clinical images

Transition to ustekinumab in patients with moderate-to-severe psoriasis and inadequate response to methotrexate: a randomized clinical trial (TRANSIT)

BACKGROUND: Limited data exist on transitioning patients with psoriasis from conventional systemic agents to biologics.OBJECTIVES: The TRANSIT study aimed to assess the efficacy and safety of two methotrexate-to-ustekinumab transition strategies.METHODS: Patients with moderate-to-severe psoriasis and inadequate methotrexate response were randomized 1 : 1 to receive ustekinumab with immediate (arm 1) or 4-week gradual (arm 2) methotrexate withdrawal. Patients weighing 64 100 kg or > 100 kg received ustekinumab 45 mg or 90 mg, respectively. The primary endpoint was the frequency of adverse events (AEs) at week 12. Secondary endpoints included additional safety, efficacy and patient-reported outcomes. We report the 12-week efficacy and safety results.RESULTS: Overall, 244 patients in arm 1 and 245 in arm 2 were randomized and received ustekinumab. Four patients per arm discontinued the trial by week 12. At week 12 in arms 1 and 2, respectively, 61% and 65% of patients experienced an AE, 2\ub79% and 2\ub74% had a serious AE, and 1\ub72% and 0\ub74% had an AE leading to ustekinumab discontinuation. In arms 1 and 2, respectively, median Psoriasis Area and Severity Index (PASI) score decreased from 15\ub72 and 15\ub74 at baseline to 2\ub79 and 2\ub78 at week 12; 58% and 62% of patients achieved a 75% reduction from baseline in PASI score (PASI 75) at week 12; median baseline Dermatology Life Quality Index fell from 8 and 9 at baseline to 1 (both arms) at week 16.CONCLUSIONS: Ustekinumab was well tolerated and effective in patients who had an inadequate response to methotrexate. Both transition strategies resulted in similar week 12 safety and efficacy outcomes