Publications

Patients with hidradenitis suppurativa (HS) are often undertreated and there are limited efficacious therapies available for treating this population. Biologics are an emerging therapeutic modality used in the management of many inflammatory conditions including HS. Implementation of biologics is typically reserved for moderate-to-severe cases or in those cases that are refractory to treatment. Though many biologics have been trialed for use in HS, only one biologic, adalimumab, is currently US FDA (Food and Drug Administration) approved for the treatment of moderate-to-severe HS. Limitations in the use of biologics for HS include the many scoring systems utilized in research studies and the relatively few well-designed, adequately powered clinical trials.

Patients with hidradenitis suppurativa (HS) often experience disease flares, which can culminate in a visit to the emergency department (ED) and inpatient admission. Appropriate management of HS patients in the acute setting is integral to controlling disease activity, limiting further sequelae, and preventing readmission. The pathophysiology of HS is poorly understood but likely involves a host of hormonal, microbial, and immunological factors. Laboratory abnormalities, including leukocytosis, thrombophilia, an elevated erythrocyte sedimentation rate, as well as an elevated C-reactive protein level, are common in HS patients and generally represent a chronic inflammatory state rather than overt infection. The Hurley staging system is an appropriate way to triage patient severity and guide treatment, as reviewed in this article. In all cases, expedited outpatient follow-up with dermatology and primary care is imperative to limiting disease morbidity.

BACKGROUND: Dermatology experiences a disproportionately high burden of prior authorizations (PAs).

OBJECTIVE: To examine the effect of a centralized pharmacy intervention on the PA process and the impact of PAs on patient outcomes.

METHODS: A retrospective review of PAs submitted for medications before and after implementation of pharmacy intervention was conducted.

RESULTS: PA was required for 8.1% of all prescriptions. PAs were most frequently submitted for topical steroids, topical antibiotics and antifungals, and topical retinoids. Most common indications included acne, psoriasis, and dermatitis. Biologic agents (55.2%) and brand-name only medications (42.8%) required PA at higher rates. Pharmacy intervention resulted in shorter time to PA submission (4 days vs 1 day, P < .001) and decision (6 days vs 1 day, P < .001) and higher approval rates (63.9% vs 80.6%, P < .001) but did not decrease the total number of PAs. Patients with approved PAs had higher likelihood of disease improvement vs those with denied PAs (71.1% vs 58.0%, P = .013).

LIMITATIONS: Data were collected from a single academic institution. Patient medication compliance was not assessed.

CONCLUSIONS: The current PA process may result in delays in care and a negative impact on patients. A centralized pharmacy intervention is an effective measure but does not eliminate the overall burden of PAs.

BACKGROUND: Weekly adalimumab (Humira® ) is approved for the treatment of hidradenitis suppurativa (HS) based on the 12-week placebo-controlled periods of the two phase III PIONEER trials.

OBJECTIVES: Using PIONEER integrated trial results, we aimed to evaluate the optimal medium-term adalimumab maintenance dosing strategy for moderate-to-severe HS.

METHODS: Each trial had two double-blind periods; 12-week Period A and 24-week Period B. Patients randomized to adalimumab 40 mg every week (ADAew) (Period A), were rerandomized in Period B to ADAew (ADAew/ew), ADA every other week (ADAew/eow), or placebo (ADAew/pbo). Placebo-randomized patients were reassigned in Period B to ADAew (PIONEER I) or placebo (PIONEER II). The primary outcome was HS Clinical Response (HiSCR). Patients who lost response during Period B were discontinued from the study and offered an option to enter the open-label extension (OLE) to receive ADAew. Results are reported across the two study periods, and data were combined from the two study periods and the OLE.

RESULTS: For week-12 HiSCR achievers, the HiSCR week-36 rate was 48·1% (ADAew/ew) vs. 46·2% (ADAew/eow) and 32·1% (ADAew/pbo). Combining (post hoc) these patients with week-12 partial responders further differentiated outcomes in Period B (ADAew/ew 55·7% vs. ADAew/eow 40·0% and ADAew/pbo 30·1%). Period-B adverse-event rates were ADAew/ew 59·6% vs. ADAew/eow 57·4% and ADAew/pbo 65·0%. One patient (ADAew/ew) reported a serious infection.

CONCLUSIONS: Weekly adalimumab treatment, effective throughout 36 weeks, was the optimal maintenance medium-term dosing regimen for this population. At least partial response after 12 weeks with continued weekly dosing had better outcomes than dose reduction or interruption. Patients who do not show at least a partial response to weekly adalimumab by week 12 are unlikely to benefit from continued therapy. No new safety risks were identified. What's already known about this topic? Hidradenitis suppurativa (HS) is a chronic inflammatory disease, commonly misinterpreted as an infection and treated with long-term antibiotic regimens or surgical incisions. Based on the chronicity of HS and the lack of evidence for efficacious and safe long-term HS treatments, it is important to evaluate medium- to long-term therapies for HS. Weekly adalimumab (Humira® ) is approved for the treatment of moderate-to-severe HS based on the two phase III PIONEER trials. What does this study add? This study pooled data from the two PIONEER trials, providing a more robust assessment of outcomes. After at least partial treatment success with weekly adalimumab short-term therapy (12 weeks), continuing weekly dosing during the subsequent 24 weeks had better outcomes than dose reduction or treatment interruption. Patients who do not show at least a partial response to weekly adalimumab by week 12 are unlikely to benefit from continued therapy.

Hidradenitis Suppurativa (HS) is a chronic debilitating skin condition that impairs the productivity and the quality of patients` lives. HS has recently drawn lots of attention among scholars to further expand their knowledge but it still loads with uncertainties and gaps to be explored. This publication addresses these uncertainties, and provides a road-map for researchers, scholars and clinicians from different disciplines for their future studies about HS. This is a proceeding report of the first Symposium on Hidradenitis Suppurativa Advances (SHSA), and it reviews the scientific sessions about the epidemiology, pathophysiology, presentations, and management of HS. This symposium was a great opportunity for experts in the HS field to exchange their knowledge, and improve their mutual understanding of this disease.

BACKGROUND: Patients with psoriasis are at an increased risk for depression. However, the impact of treatment on this risk is unclear.

OBJECTIVE: Evaluate the incidence and impact of treatment on depression among patients with moderate-to-severe psoriasis.

METHODS: We defined a study population within the Psoriasis Longitudinal Assessment and Registry and measured the incidence of depressive symptoms (Hospital Anxiety and Depression Scale-Depression score ≥8) and adverse events (AEs) of depression within cohorts receiving biologics, conventional systemic therapies, or phototherapy. Patients were evaluated at approximately 6-month intervals. Multivariate modeling determined the impact of treatment on risk.

RESULTS: The incidence rates of depressive symptoms were 3.01 per 100 patient-years (PYs) (95% confidence interval [CI], 2.73-3.32), 5.85 per 100 PYs (95% CI, 4.29-7.97), and 5.70 per 100 PYs (95% CI, 4.58-7.10) for biologics, phototherapy, and conventional therapy, respectively. Compared with conventional therapy, biologics reduced the risk for depressive symptoms (hazard ratio, 0.76; 95% CI, 0.59-0.98), whereas phototherapy did not (hazard ratio, 1.05; 95% CI, 0.71-1.54). The incidence rates for AEs of depression were 0.21 per 100 PYs (95% CI, 0.15-0.31) for biologics, 0.55 per 100 PYs (95% CI, 0.21-1.47) for phototherapy, and 0.14 per 100 PYs (95% CI, 0.03-0.55) for conventional therapy; the fact that there were too few events (37 AEs) precluded modeling.

LIMITATIONS: Incomplete capture of depression and confounders in the patients on registry.

CONCLUSION: Compared with conventional therapy, biologics appear to be associated with a lower incidence of depressive symptoms among patients with psoriasis.

Psoriasis is a chronic autoimmune disease which affects millions of people worldwide. Not only can psoriasis itself be debilitating and significantly reduce an individual's quality of life, but it is also a risk factor for other systemic disorders, such as metabolic syndrome, cardiovascular disease, and malignancy. Tremendous strides were made in the treatment of psoriasis during the mid-to-late-20th century, including the emergence of topical corticosteroids and vitamin D analogs, methotrexate, systemic retinoids, and phototherapy. However, it was not until 2004 with the advent of systemic biologic agents, which precisely target components of the immune system involved in the pathophysiological process of psoriasis, that the primary treatment benchmark increased from 50% improvement in the Psoriasis Area and Severity Index (PASI 50) to PASI 75, PASI 90, and even PASI 100, or complete resolution of cutaneous disease. Today, many patients receiving biologic therapy routinely experience greater than 75% or 90% reduction in cutaneous disease burden and a significant improvement in overall quality of life. These biologic agents are generally well-tolerated and safe but, like any medication, have associated adverse effects, some of which are predictable based on the effects of immune modulation, animal model studies, and human populations with known cytokine deficiencies. Going forward, it will be important to carefully monitor the safety profiles of these agents in both clinical trials and post-marketing surveillance registries to ensure long-term safety. It is reassuring that large safety registries are consistent in demonstrating an improved safety profile with newer and emerging biologic therapies.

BACKGROUND: Intrinsic and extrinsic factors, including ultraviolet irradiation, lead to visible signs of skin aging.

OBJECTIVE: We evaluated molecular changes occurring in photoexposed and photoprotected skin of white women 20 to 74 years of age, some of whom appeared substantially younger than their chronologic age.

METHODS: Histologic and transcriptomics profiling were conducted on skin biopsy samples of photoexposed (face and dorsal forearm) or photoprotected (buttocks) body sites from 158 women. 23andMe genotyping determined genetic ancestry.

RESULTS: Gene expression and ontologic analysis revealed progressive changes from the 20s to the 70s in pathways related to oxidative stress, energy metabolism, senescence, and epidermal barrier; these changes were accelerated in the 60s and 70s. The gene expression patterns from the subset of women who were younger-appearing were similar to those in women who were actually younger.

LIMITATIONS: Broader application of these findings (eg, across races and Fitzpatrick skin types) will require further studies.

CONCLUSIONS: This study demonstrates a wide range of molecular processes in skin affected by aging, providing relevant targets for improving the condition of aging skin at different life stages and defining a molecular pattern of epidermal gene expression in women who appear younger than their chronologic age.