Comparing the efficacy and tolerability of biologic therapies in psoriasis: an updated network meta-analysis.

BACKGROUND: The rapid expansion of psoriasis biologics has led to an urgent need to understand their relative efficacy and tolerability to inform treatment decisions better and, specifically, to inform guideline development. OBJECTIVES: To update a 2017 meta-analysis on the comparative efficacy and tolerability of biologic treatments for psoriasis. METHODS: We searched the MEDLINE, PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs), published up to 7 September 2018, of 11 licensed, NICE-approved biologics targeting tumour necrosis factor (adalimumab, etanercept, infliximab, certolizumab pegol), interleukin (IL)-12/IL-23p40 (ustekinumab), IL-17A (secukinumab, ixekizumab), IL-17RA (brodalumab) and IL-23p19 (guselkumab, tildrakizumab, risankizumab). A frequentist network meta-analysis ascertained direct or indirect evidence comparing biologics with one another, methotrexate or placebo. This was combined with hierarchical cluster analyses to consider efficacy (≥ 90% improvement in Psoriasis Area and Severity Index (PASI 90) or Physician's Global Assessment 0 or 1; PASI 75; Dermatology Life Quality Index improvement) and tolerability (drug withdrawal due to adverse events) outcomes at 10-16 weeks, followed by assessments of study quality, heterogeneity and inconsistency. RESULTS: We identified 62 RCTs presenting data on direct comparisons (31 899 participants). All biologics were efficacious compared with placebo or methotrexate at 10-16 weeks. Hierarchical cluster analyses revealed that adalimumab, brodalumab, certolizumab pegol, guselkumab, risankizumab, secukinumab, tildrakizumab and ustekinumab were comparable with respect to high short-term efficacy and tolerability. Infliximab and ixekizumab clustered together, with high short-term efficacy but relatively lower tolerability than the other agents, although the number of drug withdrawal events across the network was low, so these findings should be treated with caution. CONCLUSIONS: Using our methodology we found that most biologics cluster together with respect to short-term efficacy and tolerability, and we did not identify any single agent as 'best'. These data need to be interpreted in the context of longer-term efficacy, effectiveness data, safety, posology and drug acquisition costs when making treatment decisions.

Persistence and effectiveness of nonbiologic systemic therapies for moderate-to-severe psoriasis in adults: a systematic review.

BACKGROUND: The persistence and effectiveness of systemic therapies for moderate-to-severe psoriasis in current clinical practice are poorly characterized. OBJECTIVES: To systematically review observational studies investigating the persistence and effectiveness of acitretin, ciclosporin, fumaric acid esters (FAE) and methotrexate, involving at least 100 adult patients with moderate-to-severe psoriasis, exposed to therapy for ≥ 3 months. METHODS: MEDLINE, Embase, the Cochrane Library and PubMed were searched from 1 January 2007 to 1 November 2017 for observational studies reporting on persistence (therapy duration or the proportion of patients discontinuing therapy during follow-up) or effectiveness [improvements in Psoriasis Area and Severity Index (PASI) or Physician's Global Assessment (PGA)]. This review was registered with PROSPERO, number CRD42018099771. RESULTS: Of 411 identified studies, eight involving 4624 patients with psoriasis were included. Variations in the definitions and analyses of persistence and effectiveness outcomes prevented a meta-analysis from being conducted. One prospective multicentre study reported drug survival probabilities of 23% (ciclosporin), 42% (acitretin) and 50% (methotrexate) at 1 year. Effectiveness outcomes were not reported for either acitretin or ciclosporin. The persistence and effectiveness of FAE and methotrexate were better characterized, but mean discontinuation times ranged from 28 to 50 months for FAE and 7·7 to 22·3 months for methotrexate. At 12 months of follow-up, three studies reported that 76% (FAE), 53% (methotrexate) and 59% (methotrexate) of patients achieved ≥ 75% reduction in PASI, and one reported that 76% of FAE-exposed patients achieved a markedly improved or clear PGA. CONCLUSIONS: The comparative persistence and effectiveness of acitretin, ciclosporin, FAE and methotrexate in real-world clinical practice in the past decade cannot be well described due to the inconsistency of the methods used.

Paediatric vulval lichen sclerosus: a retrospective study.

BACKGROUND: Lichen sclerosus (LS) is a chronic inflammatory dermatosis with a predilection for the anogenital region, which mainly affects prepubertal girls and postmenopausal women. The cause is unknown, but a number of potential aetiological factors have been identified. AIM: To examine a cohort of patients with prepubertal-onset vulval LS (VLS) and assess baseline characteristics, clinical presentation, potential precipitating and predisposing factors, and response to treatment. METHODS: Data were collected from case notes on patients aged < 18 years diagnosed with prepubertal-onset VLS attending a specialist vulval dermatology service. Data included clinical presentation, comorbidities, family history, therapy and response to treatment. RESULTS: In total, 26 paediatric patients were identified. The median age at onset of symptoms was 5 years (range 2-8.5 years). Many previously identified potential aetiological factors for the development of VLS were identified, including family history, trauma, autoimmune disease and hormonal factors. A significant proportion of patients had a history of urinary tract symptoms, including incontinence and urinary tract infection. Most patients responded well to a standard course of induction topical therapy followed by maintenance therapy, but some, including three patients with ongoing urinary incontinence and three postpubertal patients, continued to have active disease. CONCLUSION: A detailed assessment is essential in patients with VLS so that potential predisposing factors and comorbidities can be identified and managed. Urinary incontinence may be implicated in the development of paediatric VLS and may prevent adequate disease control. Paediatric VLS can persist through puberty, thus long-term follow-up is advised.

Patterns of biologic therapy use in the management of psoriasis: cohort study from the British Association of Dermatologists Biologic Interventions Register (BADBIR).

BACKGROUND: Treatment modifications, including dose escalations, dose reductions, switches, discontinuations and restarts of biologics may be necessary in the management of psoriasis but the patterns of usage are incompletely defined. OBJECTIVES: To examine the treatment utilization patterns of adalimumab, etanercept and ustekinumab among biologic-naïve and non-naïve patients with psoriasis enrolled in the British Association of Dermatologists Biologic Interventions Register (BADBIR). METHODS: The study cohort included adults with chronic plaque psoriasis who were followed up for ≥ 12 months. Treatment modifications were assessed during the first year of therapy. The time-trend method, comparing the cumulative dose (CD) patients received with the recommended cumulative dose (RCD), was used to assess dosing patterns. Concomitant use of other systemic treatments was also examined. RESULTS: In total, 2980 patients (adalimumab: 1675; etanercept: 996; ustekinumab: 309) were included; 79·2% were biologic-naïve. Over 12 months, 77·4% of patients continued the biologic, 2·6% restarted therapy after a break of ≥ 90 days, 2·5% discontinued, and 17·5% switched biologic therapy. Most patients (85·7%) received the RCD of the biologic, although 8·1% were exposed to a higher CD. In total, 749 (25·1%) patients used conventional systemic therapies concomitantly with a biologic at some stage; methotrexate was used most commonly (458; 61·2%). Of those using combination therapy, 454 (60·6%) continued the use of the conventional systemic therapy for > 120 days after the start of the biologic. CONCLUSIONS: More than one-third of patients experienced treatment modifications within the first year of initiating a biologic. Conventional systemic therapies, particularly methotrexate, were commonly used concurrently, which should be considered when evaluating treatment response and adverse events to biologics in real-world observational studies.

Mid-face toddler excoriation syndrome (MiTES): a new paediatric diagnosis.

Chronic ulcerating lesions on the face are rarely seen in toddlers. Blistering disease, vasculitis, infections and self-mutilation due to neurometabolic disease can usually be excluded on clinical and histological grounds. In the absence of identifiable disease, such lesions are sometimes attributed to child abuse or fabricated illness. We describe three toddlers with chronic mid-face erosions, two from India and one from the UK. One had moderate developmental delay and one had had seizures. The lesions appeared to be self-inflicted, no underlying disease was identified and there was no suspicion of child abuse. Recognition of the same disease pattern in different continents implies a distinct pathological entity. The pattern closely resembles that seen in some patients with mutations in the pain-insensitivity genes PRDM12 and SCN11A. We suggest the term 'mid-face toddler excoriation syndrome' (MiTES) to acknowledge the existence of this condition, encourage further reports and help clarify the pathogenesis.

A case of human to human transmission of orf between mother and child.

Orf is caused by a parapoxvirus. In adults, it is commonly associated with specific occupations, whereas cases in children tend to be associated with household or recreational exposure. Spontaneous recovery usually occurs within 6 weeks. Infection in humans is believed to be through exposure to an infected animal or fomite. We present a case of a 13-month-old boy who was exposed to orf through his mother, a farmer, who had contracted the disease through administering medication to an infected animal. We believe that this may represent only the fifth case of human to human transmission of orf reported in the literature.

Traumatic retropharyngeal pseudomeningocele with atlanto-occipital dislocation in a neurologically intact patient.

Traumatic retropharyngeal pseudomeningoceles occur rarely, are associated with severe trauma, and have been reported in patients with significant neurologic deficits at presentation. We report the rare occurrence of a pseudomeningocele following a high-speed motor vehicle accident. Neurological examination showed the patient to be briskly following commands, with intact cranial nerve, motor, and sensory function. CT/MR imaging showed subarachnoid hemorrhage involving the interpeduncular cistern, a clivus fracture, a right occipital condyle fracture, an atlanto-occipital subluxation, aortic arch transection (stable and contained on CT angiogram), multiple rib fractures on the right side with associated pneumothorax, hemothorax and pulmonary contusions. His cervical spine was stabilized in a halo. He was subsequently managed in the intensive care unit and remained neurologically intact. A repeat MRI showed the interval development of a 2×1.5 cm pseudomeningocele at the craniocervical junction medial to the left occipital condyle communicating with the left anterolateral aspect of the spinal canal. Traumatic pseudomeningoceles are associated with large deceleration forces at the time of injury and are usually associated with significant neurologic deficits at presentation. However, they can arise and give rise to symptoms in a delayed fashion in trauma patients who are neurologically intact at initial presentation.

Angiographic exclusion of intracranial arteriovenous malformations using onyx®.

Historically, endovascular treatment for cerebral arteriovenous malformations (AVMs) has been reserved as an adjunct to other modalities, namely radiosurgery and microsurgery, as the cure rate for cerebral AVMs treated solely with endovascular technique and older embolic agents is low. We report a series of five consecutive patients treated successfully with Onyx®, the newest available embolic agent, with resultant angiographic cure. Five patients aged three, nine, 33, 49, and 63 years were treated endovascularly for cerebral AVMs with a total of 19 embolizations with Onyx(®). All procedures were performed under general anesthesia with biplanar fluoroscopy. Complete angiographic obliteration of the AVM nidus was obtained in all cases with no residual filling. No immediate hemorrhagic or thromboembolic complications were observed. This early experience suggests that Onyx® has excellent embolization potential, and endovascular cure of AVMs may now be achieved with single modality therapy. Long terms data needs to be collected to further validate this observation.

Tissue-engineered dermal skin grafting in the treatment of ulcerated necrobiosis lipoidica.

Necrobiosis lipoidica is a well recognized but comparatively rare cutaneous complication of diabetes mellitus. The aetiology is probably multifactorial with microangiopathy, immune complex formation, abnormal collagen synthesis and breakdown, and altered haemostasis all thought to play a part. Necrobiosis lipoidica often proves very resistant to treatment. We report a case of a 44-year-old woman with ulcerated necrobiosis lipoidica that healed following grafting with a tissue-engineered living dermal tissue.

A systematic review of antistreptococcal interventions for guttate and chronic plaque psoriasis.

BACKGROUND: Guttate psoriasis is closely associated with preceding or concurrent streptococcal infection. Some authorities have claimed that chronic plaque psoriasis may also be made worse by infection. In view of this many dermatologists have recommended using antibiotics for psoriasis, particularly guttate type. Some dermatologists have also recommended tonsillectomy for psoriasis in patients with recurrent streptococcal pharyngitis. OBJECTIVES: This review aims to assess the evidence for the effectiveness of antistreptococcal interventions, including antibiotics and tonsillectomy in the management of acute guttate and chronic plaque psoriasis. METHODS: Studies were identified by searching the Cochrane Clinical Trials Register (Cochrane Library, Issue 3, 1999), Medline (1966-September 1999), Embase (1988-September 1999), the Salford Database of Psoriasis Trials (to November 1999) and the European Dermato-Epidemiology Network (EDEN) Psoriasis Trials Database (to November 1999) for terms (STREPTOCOCC* or ANTIBIOTIC* or TONSIL*) and PSORIASIS using the Cochrane Skin Group search strategy. RESULTS: Only one trial met the selection criteria. This compared the use of two oral antibiotic schedules in 20 psoriasis patients, predominantly of guttate type, who had evidence of beta-haemolytic streptococcal colonization. Either rifampicin or placebo was added to the end of a standard course of phenoxymethylpenicillin or erythromycin. No patient in either arm of the study improved during the observation period. No randomized trials of tonsillectomy for psoriasis were identified. CONCLUSIONS: Although both antibiotics and tonsillectomy have frequently been advocated both for patients with guttate psoriasis and for selected patients with chronic plaque psoriasis, there is to date no good evidence that either intervention is beneficial.

A systematic review of treatments for guttate psoriasis.

BACKGROUND: Many different therapies are available for treating guttate psoriasis; however, there appears to be little objective evidence for their efficacy OBJECTIVES: This review aims to assess the evidence for the effectiveness of treatments for guttate psoriasis. Antistreptococcal interventions for guttate psoriasis are addressed in a separate review. METHODS: Studies were identified by searching the Cochrane Clinical Trials Register (Cochrane Library, Issue 3, 1999), Medline (1966-September 1999), Embase (1988-September 1999), Salford Database of Psoriasis Trials (to November 1999) and the European Dermato-Epidemiology Network (EDEN) Psoriasis Trials Database (to November 1999) for terms GUTTATE and PSORIASIS. We also searched 100 unselected randomized controlled trials of psoriasis therapy and all 112 randomized controlled trials of phototherapy for psoriasis in the Salford Database of Psoriasis Trials for separate stratification of guttate psoriasis. RESULTS: No published report could be found to support or to challenge current commonly used methods of management. Only one trial that met the selection criteria was identified. In this small study of 21 hospitalized patients with guttate psoriasis, intravenous infusion of an n-3 fatty acid rich lipid emulsion was compared with placebo emulsion containing n-6 fatty acids. The n-3 preparation appeared to be of some benefit for patients with guttate psoriasis. CONCLUSION: There is currently no firm evidence on which to base treatment of acute guttate psoriasis. Studies comparing standard treatment modalities, including phototherapy and topical regimens, are required to enable informed decisions on treatment choices to be made.