An indirect comparison of long-term efficacy of every-2-week dosing vs. recommended dosing of ixekizumab in patients who had static Physician's Global Assessment > 1 at week 12.

BACKGROUND: Long-term efficacy and safety of ixekizumab [160 mg at week 0, then 80 mg every 2 weeks (Q2W) for 12 weeks, followed by every 4 weeks (Q4W) thereafter (i.e. Q2W/Q4W), which is the labelled psoriasis dosing where approved, except in Japan] have been established for the treatment of adults with moderate-to-severe plaque psoriasis. However, some patients may benefit from remaining on Q2W dosing beyond 12 weeks. METHODS: Among patients who had static Physician's Global Assessment (sPGA) > 1 at week 12, efficacy through week 52 of continuous Q2W dosing in the IXORA-P study was compared indirectly with Q2W/Q4W in the integrated data from the UNCOVER-1, UNCOVER-2 and UNCOVER-3 studies. The continuous Q4W dose group, which had comparable results across studies, was used as the common comparator. RESULTS: In the IXORA-P study, among patients with sPGA > 1 at week 12, 64% of patients in the continuous Q2W group achieved sPGA ≤ 1 at week 52, which was statistically significantly higher than the 36% of patients with sPGA > 1 in the Q2W/Q4W group based on the integrated data from the UNCOVER studies (P = 0·0007). There were no clinically meaningful differences in frequencies of safety events between patients with sPGA ≤ 1 and patients with sPGA > 1 at week 12 in the IXORA-P study. CONCLUSIONS: Among patients who did not have clear or almost clear skin at week 12, nearly 30% more patients who were treated continuously with ixekizumab Q2W in IXORA-P had clear or almost clear skin at week 52 when compared indirectly with those who were treated using the labelled psoriasis dosing in integrated UNCOVER studies. What's already known about this topic? Most patients with moderate-to-severe psoriasis who were given the labelled psoriasis dosing of ixekizumab [160-mg loading dose at week 0, 80 mg every 2 weeks (Q2W) through week 12, and 80 mg every 4 weeks (QW4) thereafter] respond quickly with a high percentage of skin clearance. Additionally, patients who achieve static Physician's Global Assessment (sPGA) ≤ 1 by week 12 tend to maintain this response, even after switching to Q4W. What does this study add? Here, we assessed whether patients with sPGA > 1 at week 12 benefited from receiving more frequent dosing beyond the first 12 weeks. The results showed that Q2W dosing beyond 12 weeks resulted in more patients achieving sPGA ≤ 1 by week 52 than the labelled psoriasis dosing among patients with sPGA > 1 at week 12.

Long-term safety profile of ixekizumab in patients with moderate-to-severe plaque psoriasis: an integrated analysis from 11 clinical trials.

BACKGROUND: Psoriasis in many patients is a chronic and recalcitrant disease that requires long-term treatment, reinforcing the importance of long-term safety data. Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin (IL)-17A, is approved for treating patients with moderate-to-severe plaque psoriasis. OBJECTIVE: To determine long-term safety of ixekizumab in psoriasis. METHODS: Integrated safety data are presented from 12-week induction period, 12-60-week maintenance period, and from all ixekizumab-treated patients from 11 clinical studies. Exposure-adjusted incidence rates (IRs) per 100 patient-years are reported. RESULTS: Overall, 5689 patients accounted for 12 061.5 patient-years of ixekizumab exposure from 11 studies. Over 156 weeks, a total of 83.9% (n = 4775) of patients reported treatment-emergent adverse events (AEs). Most opportunistic infections (IR [95% confidence interval; CI] 1.8 [1.6, 2.1]) reported were mucocutaneous candidiasis. The IR (95% CI) for oral Candida infection was 0.9 (0.8, 1.1). There was no trend of increase in IR of AEs of special interest. Serious AEs were reported in 11.8% of patients; death occurred in 0.4% (n = 23) of patients. CONCLUSION: The 3-year, long-term maintenance treatment with ixekizumab did not show any new safety signals in patients with moderate-to-severe plaque psoriasis.

Efficacy and safety of ixekizumab in a randomized, double-blinded, placebo-controlled phase IIIb study of patients with moderate-to-severe genital psoriasis.

BACKGROUND: Genital psoriasis (GenPs) is a common, debilitating and difficult-to-treat manifestation of plaque psoriasis. However, few controlled, interventional studies of GenPs exist. OBJECTIVES: To determine the efficacy of ixekizumab vs. placebo in patients with moderate-to-severe GenPs with ≥ 1% involved body surface area (BSA). METHODS: Patients with moderate-to-severe GenPs, defined as a baseline static Physician's Global Assessment of Genitalia (sPGA-G) score of ≥ 3, with BSA ≥ 1% were randomized 1 : 1 to receive placebo (n = 74) or the recommended dosing of ixekizumab (n = 75). Major outcomes included the percentage of patients achieving 0 or 1 scores on the sPGA-G (primary end point), overall sPGA, GenPs Sexual Frequency Questionnaire (GenPs-SFQ) item 2, and ≥ 3-point improvement from baseline on the GenPs itch numerical rating scale. RESULTS: At week 12, ixekizumab was superior to placebo for sPGA-G 0/1 (73% vs. 8%, P < 0·001), overall sPGA 0/1 (73% vs. 3%, P < 0·001), GenPs-SFQ item 2 score of 0 or 1 (78% vs. 21%, P < 0·001) and genital itch (60% vs. 8%, P < 0·001). No candidiasis was reported, no deaths occurred and one (1%) serious adverse event was reported in a patient receiving placebo. CONCLUSIONS: Ixekizumab was superior to placebo for the treatment of moderate-to-severe GenPs with BSA ≥ 1%. The safety profile of ixekizumab was consistent with previous studies in moderate-to-severe plaque psoriasis.

The effect of bodyweight on the efficacy and safety of ixekizumab: results from an integrated database of three randomised, controlled Phase 3 studies of patients with moderate-to-severe plaque psoriasis.

BACKGROUND: There is concern that increased bodyweight may impact efficacy of some therapies used to treat psoriasis. OBJECTIVE: To evaluate the effect of bodyweight on response to ixekizumab treatment in patients with moderate-to-severe psoriasis. METHODS: Patients were characterized under three bodyweight categories (<80 kg, 80 to <100 kg, ≥100 kg) in this preplanned subgroup analysis from an integrated database of three multicenter, randomised, double-blind, controlled Phase 3 clinical studies (UNCOVER-1, UNCOVER-2 and UNCOVER-3). In the first 12 weeks of each study, patients were randomly assigned to receive subcutaneous placebo, 80-mg ixekizumab every 2 weeks (IXE Q2W) or every 4 weeks (IXE Q4W) after a starting dose of 160-mg ixekizumab, or 50-mg etanercept twice weekly (UNCOVER-2 and UNCOVER-3 only). RESULTS: This analysis included 3855 patients with baseline bodyweight in the IXE Q4W (N = 1159), IXE Q2W (N = 1168), placebo (N = 789) and etanercept (N = 739) groups. Distribution of patients across bodyweight categories was similar between treatment groups. Baseline demographics and patients characteristics were generally consistent across treatment groups within each bodyweight category. Across all bodyweight categories, a significantly higher percentage of patients treated with IXE Q2W or IXE Q4W than with placebo or etanercept achieved PASI 75, PASI 90 or PASI 100 at Week 12. No meaningful differences in PASI 75 response rates were observed across bodyweight categories. Some numerical differences in PASI 90 and PASI 100 response rates were observed between bodyweight categories with IXE Q2W providing numerically higher response rates than IXE Q4W. The incidence of treatment-emergent adverse events was similar in the treatment groups and across bodyweight categories. CONCLUSION: Ixekizumab was efficacious in the treatment of moderate-to-severe psoriasis regardless of bodyweight. The safety profile of ixekizumab was also similar across bodyweight categories, and no safety signals were identified specific to any of the bodyweight categories.

Tear break-up time in eyes with pterygia and pingueculae in Ibadan.

BACKGROUND: Ultraviolet (UV) rays and chronic irritation to dust have been implicated in the pathogenesis of degenerative conditions of the cornea and conjunctiva like pterygium and pinguecula. It has been postulated that exposure to these environmental factors cause corneal and conjunctival drying by disruption of the tear film. While some researchers have found tear film dysfunction in eyes with pterygia and pingueculae, others have found no such abnormalities. The differences in findings may be due to different methods of investigation, or differences based on geography and climate. STUDY DESIGN: The tear film has been studied using tear break-up time (TBUT) in adults with pterygia and pingueculae disorders, TBUT was measured in 73 eyes with pterygia and 74 eyes with pinguecula and were compared to TBUT in 74 eyes of age and sex matched normal controls. Abnormal TBUT was defined as TBUT less than 15 secs. Unstable tear film was defined as TBUT less than 10 secs. RESULTS: The mean TBUT was lower in eyes with pterygia (17.90 secs) than in control eyes (19.86 secs), although the mean difference was not statistically significant. Abnormal TBUT, defined as TBUT less than 15 secs, was found in 29 eyes out of 73 eyes with pterygia (39.7%), compared with 13 eyes out of 74 eyes with pingueculae (17.6%) and in 17(23.0%) of 74 control eyes (X2 = 10.01, df = 2, P = 0.0006). A TBUT of less than 15 secs was more significantly associated with eyes with pterygia compared to control eyes. Unstable tear film (TBUT less than 10 secs) was found in 12(16.4%) eyes with pterygia, compared to 4(5.4%) eyes with pingueculae and 4(5.4%) control eyes. Unstable tear film was significantly associated with eyes with pterygia (P = 0.027). CONCLUSION: Tear film abnormalities are associated with pterygium but not with pinguecula in the subjects studied. TBHT may vary in different populations.

Filarial worm (Loa loa) in the anterior chamber. Report of two cases.

Two Nigerian patients with intraocular parasitism by adult Loa loa worms are reported. Whereas Loa loa infestation of the subcutaneous tissues around the eye usually has no permanent effect on visual acuity, in the two cases reported the affected eye became blind.

Age-related eye disease in the elderly members of rural African community.

The results of eye examination of the elderly persons (above age sixty years) in a rural population in south-western Nigeria are presented. The group comprised only 8.4% of the total population of the village studied, but its members constituted 37% of the persons with blindness and low vision and 27.9% of the persons with ocular abnormalities. Cataract was the commonest cause of blindness and low vision. Age-related macular degeneration (ARMD) and glaucoma were also important causes. Seven of the 208 members of the community aged above sixty years had demonstrable ARMD. This incidence is much higher than found in hospital studies performed earlier. The study demonstrates clearly the fact that blindness prevalence increases with age and highlights the causes of blindness and low vision in this population. An early, well-structured approach to age-related eye diseases is suggested, to prevent it from being a serious problem.

Neuro-ophthalmological sequelae of sickle cell disease. A case report and review of the literature.

A case of homozygous sickle cell anaemia male patient, aged 16 years is reported. The initial symptom following a sickle cell crisis was impairment of vision, progressing rapidly to complete blindness within three days. Within 4 days of admission in the hospital, he lapsed into coma and died four weeks later. Autopsy findings revealed multiple cerebral, pontine and cerebellar infarcts. The literature on neuro-ophthalmological sequelae is reviewed.

Ocular gun-shot injuries in Ibadan.

Twenty patients with eye injuries resulting from gun-shots were admitted to the University College Hospital, Ibadan, over a 10-year period. Three of the patients had involvement of both eyes, making a total of 23 eyes. Seven eyes had contusion injuries, while 16 had perforating injuries. Eight of the perforating group had primary evisceration, two refused evisceration and six had repair of corneal/corneo-scleral wounds. All seven eyes in the contusion group were treated conservatively and four retained a vision of better than 6/36. Seven out of the 20 patients were shot by someone else, six of whom were armed robbers. The other 13 patients were shooting animals while hunting, when the gun either backfired or exploded in their faces.

Eye care outreach to an underserved rural population in Oyo State.

This paper is essentially an initial assessment of work done through a rural community outreach programme based in the ophthalmology department of a large teaching hospital. It evaluates the accessibility, acceptability, and initial effectiveness of the programme by presenting information on selected variables. The evaluation is used to assess the initial achievements of the programme against the planned objectives.

Sebaceous gland carcinoma of the eyelid: case report.

This paper reports a case of sebaceous adenocarcinoma of the meibomian gland in a 69-year-old man. The tumour was excised and histopathological examination revealed the characteristic features of sebaceous adenocarcinoma.

Ocular morbidity survey in an opthalmically underserved rural area of Nigeria.

This paper describes in some detail a prevalence of blindness study conducted in a rural area of South-Western Nigeria, which is served by a peripheral eye clinic. By a stratified random cluster-sampling procedure, 1975 people in ten villages were selected for ocular examination. Community prevalence rate of ocular morbidity was 3.3% with the highest prevalence in the 51-60 years age group. There was a male-female ratio of 4:3 and the prevalence of ocular morbidity in the 31-50 years age group was most significant, but people in this age group seldom reported at the peripheral eye clinic serving the survey areas. Age-related macular degeneration was found to be prevalent in the community, while few cases were reported at the peripheral eye centre. The information gathered in the survey is being used to plan and improve eye care services from the peripheral eye clinic. Case finding in persons aged 31-50 years and those at risk for age-related macular degeneration has been recommended as part of the programme of the peripheral eye clinic.

Complicated migraine and Haemoglobin AS in Nigerians.

Among 123 Nigerians with migraine seen at one clinic 49 (40%) had complicated migraine, with ophthalmoplegia in 20 and amaurosis or field defects in 13. Haemoglobin AS was found in 60% of patients with complicated migraine, compared with 20% of those with simple migraine.

Expression of CCR-5/CXCR-4 in spinal cord of patients with AIDS.

The discovery that chemokines and their receptors (in particular CXCR-4 and CCR-5) play a role in HIV infection challenges traditional views on the pathogenesis of HIV infection in man and identifies new potential targets for therapeutic intervention. Several groups as well as our pilot study have found that increased numbers of CCR-5 positive macrophage/microglia correlate with disease severity in brains of patients with AIDS. Among HIV-related disorders, vacuolar myelopathy (VM) is the most common spinal cord disorder in patients with AIDS. The purpose of this study was to investigate the possible relationship between the expression of CCR-5/CXCR-4 and spinal cord pathology in patients with AIDS. Thirty-four spinal cords (forming two groups: without and with VM) of patients with AIDS and 6 HIV-1-negative controls were investigated by routine histological examination and immunohistochemistry. Elevated expression of CXCR-4 was found in most AIDS cases with/without neuropathological disorders (8/17 and 13/16, respectively). No CCR-5 expression was detected in HIV-1-negative controls. Among 34 cases with AIDS, expression of CCR-5 was detected in 1/16 HIV-1-positive normal spinal cords and 5/18 with VM. Despite the lack of statistical significance between the two groups (P=0.1019), our results suggest that CCR-5/CXCR-4 are present in spinal cord of patients with AIDS and that CCR-5 is more frequently found in association with VM.

Effect of etomidate on intra-ocular pressure.

Etomidate, a new short-acting non-barbiturate hypnotic, was administered to 40 patients between the ages of 12 years and 65 years. Intra-ocular pressure was measured before and after etomidate injection using a Schiotz tonometer. A significant reduction of intra-ocular pressure was found to follow etomidate injection in spite of the often associated myoclonic movements. The mechanism of reduction of intra-ocular pressure has not been determined in this study. It is suggested that etomidate will be a useful intravenous induction agent where elevation of intra-ocular pressure is undesirable.