Background In patients with Crohn's disease, the efficacy of ustekinumab, a human monoclonal antibody against interleukin-12 and interleukin-23, is unknown. Methods We evaluated ustekinumab in adul...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa1203572

Ustekinumab Induction and Maintenance Therapy in Refractory Crohn's Disease

Importance Hidradenitis suppurativa (HS) is relatively common, with the prevalence of 0.05% to 4.10%, yet many patients receive inadequate treatment. Objective To review the diagnosis, epidemiology, and treatment of HS with an emphasis on advances in the last 5 years. Evidence Review A literature search was conducted using PubMed, MEDLINE (Medical Subject Headings [MeSH]), and EMBASE to include recently published treatment studies (searched from September 1, 2011, to May 1, 2017). Reviews, guidelines, conference abstracts, and studies with less than 10 patients were excluded. Furthermore, internet searches for guidelines on hidradenitis suppurativa using Baidu, Bing, Google, and Qwant browsers were performed. Findings The diagnosis of HS is made by lesion morphology (nodules, abscesses, tunnels, and scars), location (axillae, inframammary folds, groin, perigenital, or perineal), and lesion progression (2 recurrences within 6 months or chronic or persistent lesions for ≥3 months). HS is more common than was previously thought based on epidemiological analysis (0.05%-4.10%). Disability from HS can be significant. Patients with HS may have significant comorbidities (eg, obesity, metabolic syndrome, diabetes, and arthritis) and increased all-cause mortality (incidence rate ratio, 1.35 [95% CI, 1.15-1.59]). Antibiotic treatment with combinations of clindamycin and rifampicin, or ertapenem followed by combination rifampicin, moxifloxacin, and metronidazole for 6 months is effective. Adalimumab is effective in a significant proportion of patients and treatment with IL-1 and IL-12 receptor subunit beta 1 (Rb1) antibodies may also be useful. Tissue-sparing surgical techniques and carbon dioxide laser treatments also are available, but the evidence on clinical outcomes with these approaches is limited. Conclusions and Relevance Hidradenitis suppurativa is more common than previously thought and may be treated by an array of pharmacological and surgical techniques. Hidradenitis suppurativa should be considered in the differential diagnosis of nodular lesions or sinus tracts present in the axillae, groin, perineal, and mammillary fold regions.

https://jamanetwork.com/journals/jama/articlepdf/2664466/jama_Saunte_2017_rv_170008.pdf

Hidradenitis Suppurativa: Advances in Diagnosis and Treatment

BackgroundLittle is known about the effect of specific anti–interleukin-23 therapy, as compared with established anti–tumor necrosis factor therapies, for the treatment of moderate-to-severe plaque psoriasis. MethodsIn a 52-week, phase 2, dose-ranging, randomized, double-blind, placebo-controlled, active-comparator trial, we compared guselkumab (CNTO 1959), an anti–interleukin-23 monoclonal antibody, with adalimumab in patients with moderate-to-severe plaque psoriasis. A total of 293 patients were randomly assigned to receive guselkumab (5 mg at weeks 0 and 4 and every 12 weeks thereafter, 15 mg every 8 weeks, 50 mg at weeks 0 and 4 and every 12 weeks thereafter, 100 mg every 8 weeks, or 200 mg at weeks 0 and 4 and every 12 weeks thereafter) through week 40, placebo, or adalimumab (standard dosage for psoriasis). At week 16, patients in the placebo group crossed over to receive guselkumab at a dose of 100 mg every 8 weeks. The primary end point was the proportion of patients with a Physician’s Global Asse...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa1501646

A Phase 2 Trial of Guselkumab versus Adalimumab for Plaque Psoriasis.

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is characterized by chronic inflammation, a relapsing and remitting clinical course, requirement for lifelong medication and often, significant morbidity. While multiple effective therapeutic options exist for the treatment of IBD, a proportion of patients will either fail to respond or lose response to therapy. Advances in therapeutics, such as the gut-specific anti-integrins, now offer patients an alternative option to systemic immunosuppression. Anti-interleukin 12 (anti-IL-12)/IL-23 agents offer new and effective treatment options for CD, while the oral small molecules now offer an oral alternative for the treatment of moderate-to-severe disease, previously requiring subcutaneous injection or intravenous infusion. Alternatives to pharmacological treatment such as stem-cell transplant and faecal microbiota transplant are also showing some promise in the treatment of both CD and UC.

https://journals.sagepub.com/doi/pdf/10.1177/2040622319899297

Emerging treatments for inflammatory bowel disease

Psoriatic arthritis (PsA) increases the disease burden associated with psoriasis by further diminishing quality of life, increasing health care costs and cardiovascular risk, and potentially causing progressive joint damage. The presence of PsA influences psoriasis treatment by increasing overall disease complexity and, within the framework of current guidelines and recommendations, requiring the use of conventional disease-modifying anti-rheumatic drugs or tumor necrosis factor-α inhibitors in order to prevent progressive joint damage. Despite its important impact, PsA is still under-diagnosed in dermatology practice. Dermatologists are well positioned to recognize and treat PsA, given that it characteristically presents, on average, 10 years subsequent to the appearance of skin symptoms. Regular screening of psoriasis patients for early evident joint symptoms should be incorporated into daily dermatologic practice. Although drugs effective in PsA are available, not all patients may respond to treatment, and others may lose their initial response over time. New investigational therapies, such as inhibitors of interleukin-17A, interleukin-12/23, Janus kinase 3, or phosphodiesterase-4, may address unmet needs in psoriatic disease, with further research needed to determine the role of these agents in reducing joint damage and other comorbidities.

Burden of Disease: Psoriasis and Psoriatic Arthritis

Monoclonal antibody (mAb) therapy was first established upon the approval of a mouse antibody for treatment of human acute organ rejection. However, the high incidence of immune response against the mouse mAb restricted therapeutic utility. Development of chimeric, “humanized” and human mAbs broadened therapeutic application to immune-mediated diseases requiring long-term treatment. Indeed, mAb therapeutics targeting soluble cytokines are highly effective in numerous immune-mediated disorders. A recent example is ustekinumab, a first-in-class therapeutic human immunoglobulin G1 kappa mAb that binds to the interleukins (IL)-12 and IL-23, cytokines that modulate lymphocyte function, including T-helper (Th) 1 and Th17 cell subsets. Ustekinumab was generated via recombinant human IL-12 immunization of human immunoglobulin (hu-Ig) transgenic mice. Ustekinumab binds to the p40 subunit common to IL-12 and IL-23 and prevents their interaction with the IL-12 receptor β1 subunit of the IL-12 and IL-23 receptor comp...

https://www.tandfonline.com/doi/pdf/10.4161/mabs.3.6.17815

Discovery and mechanism of ustekinumab: A human monoclonal antibody targeting interleukin-12 and interleukin-23 for treatment of immune-mediated disorders

The Fully Human Antibody CNTO1275 Effectively Inhibits Human IL-12 and IL-23 Mediated Th1 and Th17 Cell Function and Provides Clinical Benefit to Patients with Plaque Psoriasis

The Role of Protein Excipient in Driving Antibody Responses to Erythropoietin

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Discovery and mechanism of ustekinumab: A human monoclonal antibody targeting interleukin-12 and interleukin-23 for treatment of immune-mediated disorders

The Fully Human Antibody CNTO1275 Effectively Inhibits Human IL-12 and IL-23 Mediated Th1 and Th17 Cell Function and Provides Clinical Benefit to Patients with Plaque Psoriasis

The Role of Protein Excipient in Driving Antibody Responses to Erythropoietin