Open-label study of etanercept treatment in patients with moderate-to-severe plaque psoriasis who lost a satisfactory response to adalimumab.

BACKGROUND: Some patients with plaque psoriasis experience secondary failure of tumour necrosis factor inhibitor therapy. OBJECTIVES: To evaluate efficacy, safety and patient-reported outcomes (PROs) with etanercept in patients with secondary adalimumab failure. METHODS: This phase IV open-label single-arm estimation study (NCT01543204) enrolled patients on adalimumab who had achieved static Physician's Global Assessment (sPGA) score 0/1 (clear/almost clear). Patients subsequently lost response, defined as sPGA ≥ 3 or loss of 50% improvement in Psoriasis Area and Severity Index (PASI 50). At baseline, patients had involved body surface area ≥ 10%, sPGA ≥ 3 and PASI ≥ 10. Antiadalimumab antibodies (ADAs) were measured at screening. Patients received etanercept 50 mg twice weekly for 12 weeks, followed by 50 mg weekly. The primary end point was sPGA 0/1 at week 12 (intention-to-treat analysis; no hypothesis tested). Additional outcomes included rates of sPGA 0/1, PASI responses, safety, PROs of itch, pain and flaking, Dermatology Life Quality Index, treatment satisfaction and Work Productivity and Activity Impairment questionnaire. RESULTS: Sixty-four patients enrolled; 67% had ADAs. sPGA 0/1 rates at week 12 were 39·7% [95% confidence interval (CI) 27·6-52·8; primary end point] and 45% (95% CI 29·3-61·5) for patients positive for ADAs and 35% (95% CI 15·4-59·2) for patients negative for ADAs. PASI 75 response rates at week 12 were 47·5% (95% CI 31·5-63·9) for patients who were positive for ADAs and 50% (95% CI 27·2-72·8) for patients negative for ADAs. No new safety signals were observed. PROs of itch, pain and flaking consistently improved at week 12 and were maintained through week 24. CONCLUSIONS: Patients with psoriasis who experienced secondary failure of adalimumab achieved satisfactory response to etanercept regardless of ADA status.

Oral iloprost treatment in patients with Raynaud's phenomenon secondary to systemic sclerosis: a multicenter, placebo-controlled, double-blind study.

OBJECTIVE: To evaluate the efficacy and tolerability of an oral preparation of iloprost, a prostacyclin analog, in patients with Raynaud's phenomenon (RP) secondary to systemic sclerosis (scleroderma). METHODS: A multicenter, randomized, parallel-group, placebo-controlled double-blind study was performed at university and community-based medical centers. Patients were randomly assigned to receive either 50 microg of iloprost orally twice daily or an identical gelatin-coated capsule containing placebo for 6 weeks. Outcome measures included average total daily duration of RP attacks, average number of RP attacks, and RP condition scored via a standardized daily diary. RESULTS: Three hundred eight patients with scleroderma (272 women, 36 men, mean age 49 years [range 18-80]) were enrolled. One hundred fifty seven were assigned to receive iloprost and 151 to receive placebo. One hundred forty-three patients in the iloprost group (91.1%) and 144 in the placebo group (95.4%) completed the 6-week treatment phase. Fifteen of these treated patients (8 iloprost, 7 placebo) failed to complete all of the followup visits. The mean reduction in the average duration of attacks from baseline to week 5-6 was 24.32 minutes in the iloprost group and 34.34 minutes in the placebo group (P = 0.569). Likewise, the mean reduction from baseline to week 5-6 in the daily frequency of attacks was 1.02 in the iloprost group and 0.83 in the placebo group (P = 0.459). The Raynaud's condition score, a patient-completed assessment of the severity of RP attacks, was reduced by 1.32 in the iloprost group and 1.00 in the placebo group (P = 0.323). The lack of significant difference between treatment groups did not change when a variety of factors, including use of other vasodilators, duration of disease, classification of scleroderma (limited versus diffuse), or number of baseline digital ulcers were taken into account. Premature withdrawal from the study due to adverse events occurred in 10 patients (6.4%) in the iloprost group and 3 (2.0%) in the placebo group (P = 0.058). CONCLUSION: Oral iloprost at a dosage of 50 microg twice daily is no better than placebo for management of RP secondary to scleroderma, either during 6 weeks of treatment or during 6 weeks of posttreatment followup.

Developmental shifts in the ability of infants with Down syndrome to produce treadmill steps.

BACKGROUND AND PURPOSE: In this study, we used a dynamic systems strategy to examine longitudinally the ability of infants with Down syndrome to produce alternating steps when supported on a motorized treadmill. SUBJECTS: Seven infants participated, ranging in age from 8 to 11 months at entry into the study and 13 to 29 months at their final session. METHODS: Data were collected in the infants' homes on a monthly basis. Testing continued until each subject produced consistent alternating step patterns during three consecutive test sessions. RESULTS: All infants responded by producing alternating steps, on average, 13.3 months before they walked independently, but they initiated this response at a wide range of chronological ages and significantly later than reported previously for nondisabled infants. Similar developmental variables (control parameters) marked the shift into responsiveness to the treadmill context for all infants with Down syndrome, but these variables differed from those identified for nondisabled infants. CONCLUSION AND DISCUSSION: With age, alternating treadmill stepping became a more stable response, although the relative timing of interlimb coordination (phase lag) of the step cycles remained quite variable across ages. We discuss our results relative to the usefulness of dynamic systems theory in understanding delayed development and the possibilities of pursuing the treadmill paradigm as an intervention approach.

Alternating stepping patterns: hidden abilities of 11-month-old infants with Down syndrome.

Normally developing infants can produce organized alternating stepping patterns long before they stand alone or attempt to walk, if supported upright on a motorized treadmill. The purpose of this study was to examine whether infants with Down syndrome, who begin to walk at a much later age than non-disabled infants, could produced alternating steps in a similar way. Six of the seven 11-month-old infants studied responded to the treadmill stimulus by producing alternating steps. This suggests that the basic neural substrate necessary for upright locomotion is available long before walking occurs in infants with Down syndrome, as it is in normally developing infants. The infants in this study began to walk at an average of 13.3 months after demonstrating the ability to produce treadmill steps.

Hypertrophic osteoarthropathy associated with achalasia.

A case of hypertrophic osteoarthropathy associated with achalasia is reported. The signs and symptoms of hypertrophic osteoarthropathy abated after treatment of the patient's achalasia with Heller's myotomy. A review of the literature regarding the cause of hypertrophic osteoarthropathy is discussed briefly.

Hypothesis: the nervous system may contribute to the pathophysiology of rheumatoid arthritis.

No current theory of the mechanisms involved in the pathophysiology of rheumatoid arthritis (RA) explains its important clinical features. We hypothesize that neural mechanisms are involved in this pathophysiology and they explain at least 3 clinical features: specific high risk joints are more likely to develop arthritis; specific high risk joints have more severe arthritis; and RA is bilaterally symmetric. If our hypothesis is correct, it will provide a rationale for the development of new therapies for what is now an inadequately treated disease.

Anticollagen antibodies and immune response gene products in rheumatoid arthritis.

Circulating antibodies to native and denatured types I and II human and bovine collagens were assayed in patients with rheumatoid arthritis (RA), patients with other rheumatic diseases, and normal individuals. A subgroup of this population was also assayed for reactivity with typing reagents which detect determinants (MT and HLA-DR) present in human immune response gene products. The mean titers of antibodies to each collagen tested were not significantly higher in RA patients when compared with patients who had other rheumatic diseases. Although both MT3 and MT4 were significantly associated with RA, there was no significant association between the anticollagen antibodies and any MT type or HLA-DR4. These studies raise a question concerning the role of collagen antibodies in the pathogenesis of RA and suggest that genes distinct from those coding for HLA-DR may play a role in the expression of the disease.