Faculty Bibliography

BACKGROUND: Refractory patients with moderate-to-severe psoriatic arthritis (PsA) are commonly managed by switching between anti-TNFs.
OBJECTIVE(S): To evaluate the effectiveness of switching between anti- TNFs using a systematic review of the literature.
METHOD(S): MEDLINE- and Embase-indexed English-language publications were systematically searched from 1995-May 2015 for studies assessing real-world effectiveness outcomes of anti-TNF cycling in PsA patients.
RESULT(S): Among 1,086 unique citations identified, 48 were retrieved, and 18 studies and meeting abstracts were included. In 7 studies, 2,932 patients were tested for the association between consecutive treatment lines and effectiveness, 6 of which found significant differences between lines of anti-TNF therapy. Effectiveness measures varied widely. Only 7 of 18 measures were common across studies: ACR 20, 50, and 70, CRP, DAS28, PASI, and drug survival. In the NOR-DMARD multi-center study, significant improvement for ACR 70 (23.7% vs. 12.5%; P = 0.04) and mean change in CRP (P = 0.001) was observed for 1st-line relative to 2nd-line therapy. Likewise, in a Danish registry (DANBIO), response defined as ACR 20, 50, 70, and mean DAS28 scores were significantly improved with 1st-line vs. 2nd-line anti-TNF use. In an Italian hospital cohort, PASI 50 and 75 responses at Week 24 were also comparatively higher in the 1st line compared to 2nd line. Drug survival declined from initial anti-TNF to the 2nd and 3rd line in the DANBIO study (P < 0.0001), and from 1st line to 2nd line in a Norwegian clinical study (P < 0.001), but no drug survival loss was observed in a 12-year French cohort. When later lines were tested, no differences in CRP or PASI mean change were detected between 2nd- and 3rd-line anti-TNFs, in a second Italian hospital study. In the only study with multivariate regression testing for predictors of response, DANBIO patients were less likely to respond (ACR 20 or 50) to a second anti-TNF course if safety rather than lack of effect caused them to switch (odds ratio [OR] 0.04; P = 0.003 and OR 0.05; P = 0.03, respectively).
CONCLUSION(S): Effectiveness of anti-TNFs in 2nd-line and later has been reported in few real-world studies of PsA patients. Subsequent treatment lines may be associated with less response in some measures. Comparisons across studies are hampered by a lack of shared outcomes and studies that test for differences by treatment line. More research is needed to quantify the effectiveness of sequential anti-TNF lines in this progressive population and to compare these effects with response to drugs with a different mechanism of action

Introduction: Several studies have shown that obesity is more common among patients with psoriasis and psoriatic arthritis, and this correlation may be related to the systemic inflammation associated with obesity. Although bariatric surgery has been shown to improve several obesity-related comorbidities, the effects of surgical weight loss on psoriasis and psoriatic arthritis have not been adequately studied. Our objective was to investigate the effects of weight loss from bariatric surgery on psoriasis and psoriatic arthritis. Methods: A retrospective database of 9,073 bariatric surgeries performed at a single center between 2002 and 2013 was queried. Patients with a diagnosis of psoriasis prior to bariatric surgery were identified. Preoperative demographic, anthropometric, and comorbidity data were collected. Patients were contacted about their history of psoriasis, changes in symptoms after surgery, diagnosis of psoriatic arthritis, and treatment modalities for psoriasis and psoriatic arthritis pre- and postoperatively. The primary outcome was the percentage of patients who reported improvement in psoriasis after surgery. Secondary analyses were performed to define factors associated with improvement in psoriasis. Results: We identified 128 patients with a preoperative diagnosis of psoriasis. Seventy-four (58%) patients completed the study. Baseline patient characteristics are listed in Table 1. The mean time from surgery was 6.2 years, with a mean excess weight loss (EWL) of 46.5%. At the time of contact, forty-one (55%) patients reported improvement in their psoriasis, 24.3% reported improvement with subsequent relapse, 6.8% had no change, and 12.6% reported that their psoriasis progressively worsened. Sixteen (22%) patients also had a preoperative diagnosis of psoriatic arthritis; 62.5% reported improvement in their psoriatic arthritis, whereas 19% had no change and 19% worsened. In secondary analyses, lower preoperative BMI (43.7kg/m² vs. 48.4 kg/m², p=0.004) was found to be independently associated with postoperative improvement in psoriasis. Patients with severe psoriasis at the time of surgery and significant postoperative improvement, excluding those whose improvement may have been due to escalation in medication class, demonstrated greater weight loss (101.4 lb vs. 66.0 lb, p=0.025) and EWL (63.7% vs. 44.7% EWL, p=0.028). Similarly, improvement in psoriatic arthritis was associated with greater EWL, but this did not reach statistical significance (51.4 vs. 48.3, p=0.815). Conclusion: Although the natural history of psoriasis and psoriatic arthritis is typically chronic, a majority of patients experience improvement after bariatric surgery. Based on our results, there is an association between excess weight loss and symptomatic improvement in severe cases of psoriasis. Factors such as lower preoperative BMI may be used to identify those patients with a greater likelihood of remission. Additionally, ours is the first study to show an improvement in psoriatic arthritis after bariatric surgery and a possible association between surgical EWL and improvement in psoriatic arthritis. Larger prospective studies are needed to further define the true effect of surgical weight loss on psoriasis and psoriatic arthritis

OBJECTIVE: To characterize the diversity and taxonomic relative abundance of the gut microbiota in patients with never-treated, recent-onset psoriatic arthritis (PsA). METHODS: High-throughput 16S ribosomal RNA pyrosequencing was utilized to compare the community composition of gut microbiota in patients with PsA (n = 16), patients with psoriasis of the skin (n = 15), and healthy, matched control subjects (n = 17). Samples were further assessed for the presence and levels of fecal and serum secretory IgA (sIgA), proinflammatory proteins, and fatty acids. RESULTS: The gut microbiota observed in patients with PsA and patients with skin psoriasis was less diverse when compared to that in healthy controls. This could be attributed to the reduced presence of several taxa. Samples from both patient groups showed a relative decrease in abundance of Coprococcus species, while samples from PsA patients were also characterized by a significant reduction in Akkermansia, Ruminococcus, and Pseudobutyrivibrio. Supernatants of fecal samples from PsA patients revealed an increase in sIgA levels and decrease in RANKL levels. Analysis of fatty acids revealed low fecal quantities of hexanoate and heptanoate in both patients with PsA and patients with psoriasis. CONCLUSION: Patients with PsA and patients with skin psoriasis had a lower relative abundance of multiple intestinal bacteria. Although some genera were concomitantly decreased in both conditions, PsA samples had a lower abundance of reportedly beneficial taxa. This gut microbiota profile in PsA was similar to that previously described in patients with inflammatory bowel disease and was associated with changes in specific inflammatory proteins unique to this group, and distinct from that in patients with skin psoriasis and healthy controls. Thus, the role of the gut microbiome in the continuum of psoriasis-PsA pathogenesis and the associated immune response merits further study.

Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis that can lead to decreased health-related quality of life and permanent joint damage leading to functional decline. In addition to joint and skin manifestations, both psoriasis and PsA are associated with numerous comorbidities and extraarticular/cutaneous manifestations, which may influence the physician's choice of therapy. The objectives of this review are (1) to identify comorbidities in patients with PsA based on the available evidence; (2) to examine the effects of these comorbidities or extraarticular/cutaneous manifestation on the management of patients with PsA as well as the selection of therapy; and (3) to highlight research needs around comorbidities and treatment paradigms. This review is part of a treatment recommendations update initiated by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).

Psoriasis is a chronic inflammatory skin condition, characterized by T-helper (Th) 1 and Th17 cell activation. Ustekinumab is a fully human immunoglobulin G1kappa monoclonal antibody that targets the common p40 subunit that is shared by both interleukin (IL)-12 and IL-23, consequently inhibiting T-cell differentiation along both Th1 and Th17 pathways. This is a report of two patients who developed psoriatic arthritis during ustekinumab treatment for psoriasis. Neither patient had a personal or family history of arthritis.