Anti-drug antibodies in psoriasis: a critical evaluation of clinical significance and impact on treatment response

TNF inhibitors and anti-p40IL12/23 monoclonal antibodies are efficacious treatments for moderate-to-severe psoriasis. However, the formation of anti-drug antibodies (ADA) with biologics may prevent patients from achieving a full clinical response. ADA have been reported in patients treated with etanercept, infliximab, adalimumab or ustekinumab at rates of 0–18.3%, 5.4–43.6%, 8.8–44.8% and 3.8–5.4%, respectively. Antibodies against etanercept have no apparent effects on clinical response, whereas antibodies against infliximab or adalimumab have been associated with diminished clinical response. The significance of ADA against ustekinumab is yet to be determined. Data regarding management strategies to counteract ADA formation and their effects are limited in psoriasis patients. However, some evidence suggests that concomitant immunomodulators such as methotrexate may suppress ADA development in psoriasis. ADA specific to one biologic do not appear to carry cross-linking potential with other biologic agents. ADA formation needs to be considered as a possible factor contributing to diminished response from biologic agents.     

Pneumocystis jirovecii pneumonia in a patient with pustular psoriasis with an IL‐36RN deficiency treated with infliximab: Case report and review of the literature

Pneumocystis jirovecii pneumonia (PCP) is a relatively rare complication in non‐HIV patients receiving immunosuppressive treatment. Since the introduction of tumour necrosis factor‐α inhibitors cases of this complication have increased. We report the case of a 54‐year‐old, HIV‐negative patient, who presented to our department with a long history of pustular psoriasis with poor response to traditional treatments. During the last admission he developed a severe flare that was unresponsive to cyclosporine, therefore infliximab was initiated. After the third dose he developed PCP that required admission to the intensive care unit, with a positive response to i.v. administration of trimethoprim/sulfamethoxazole. During follow up a mutation in the IL36RN gene compatible with an IL‐36RN deficiency was found and anakinra was started, with rapid improvement of his psoriasis. PCP is a severe complication in patients receiving immunosuppressive therapy and is probably underreported by dermatologists. There are no clinical guidelines for PCP prophylaxis in dermatological patients who will receive immunosuppressive or biological treatments. We believe that it is necessary to report the cases of PCP to assess the real impact of this complication and develop appropriate prophylaxis guidelines.     

Rescue therapy: ciclosporin or infliximab?

Evaluation of: Laharie D, Bourreille A, Branche J et al.; Groupe d’Etudes Thérapeutiques des Affections Inflammatoires Digestives. Ciclosporin versus infliximab in patients with severe ulcerative colitis refractory to intravenous steroids: a parallel, open-label randomised controlled trial. Lancet 380(9857), 1909–1915 (2012).

Severe active refractory ulcerative colitis is a potentially life-threatening disease. The introduction of intensive steroid treatment and early surgery has reduced mortality in recent years. Ciclosporin and infliximab are effective rescue therapies in steroid refractory colitis. A head-to-head study proposed by Laharie et al. failed to demonstrate the superiority of ciclosporin but confirmed the efficacy and safety of infliximab to control active disease and to maintain remission.     

Efficacy of combined anti-TNF-alpha and surgical therapy in perianal and enterocutaneous fistulizing Crohn’s disease – clinical observations from a tertiary Eastern European center

Abstract

Background and aims. Recently, anti-TNF-alpha therapy has increasingly been used in the treatment of perianal Crohn’s disease (PCD), but there is only limited data regarding its short- and long-term efficacy. Material and methods. The medical records of 68 patients treated with anti-TNF-alpha for PCD were assessed retrospectively. Rate of complex fistulas was 75%. Every patient received induction therapy, but in 20 cases the treatment was discontinued before week 52 due to funding regulations, an allergic reaction, or compliance problems. On week 12, the luminal activity decreased in more than 80% of the cases and the complete remission (CR) rate was about 60%; by the end of the first year, this ratio did not change substantially. Complete fistula closure was achieved in 26 cases (38.3%) and 53 patients (51.5%) showed a partial response during the 1-year period. Regarding both perianal and luminal activities, CR rate was achieved in 23 cases (33.8%). However, after the biological therapy was discontinued, recurrence of fistulas could be detected in every second patient. Additional surgical intervention was performed in 45% of patients during the 1-year period (seton drainage of fistulas and abscess drainage). Conclusion. The anti-TNF-alpha therapy combined with surgery is an effective treatment of PCD. Approximately every third patient revealed complete fistula closure, while half of the other cases showed a partial response. Due to the high rate of fistula recurrence after stopping the biological therapy, more than 1 year of anti-TNF-α treatment may be beneficial.     

Emerging biotherapies for Sjögren's syndrome

Importance of the field: Sjögren's syndrome (SS) is an autoimmune epithelitis. This exocrinopathy is frequently associated with extraglandular complications, and the patients are at risk of developing B cell lymphoma. Given the lack of disease-modifying drugs, and the fact that SS is a quintessential B-cell mediated disease, attention has recently been focused on biotherapies.

Areas covered in this review: Despite negative grounds, TNF-α antagonists have been tested in the disease, and proven not be efficient. However, B-cell depleting therapy using anti-CD20 antibodies such as rituximab, which is a chimeric mAb, has shown promise in the field, while anti-CD22 mAb seems to be less active.

What the reader will gain: New treatments against the B-cell activating factor of the TNF family are about to be tested, or replaced by receptor immunoglobulin decay protein.

Take home message: B-cell depleting therapies seem promising in SS, but no data are, thus far, available on treatments targeting B-cell activating factor of the TNF family.     

Efficacy and safety of infliximab as rescue therapy for ulcerative colitis refractory to tacrolimus

Background and Aim: Little is known about the efficacy and safety of infliximab for ulcerative colitis refractory to tacrolimus. The aim of this study was to evaluate the efficacy and safety of infliximab in the induction of remission in ulcerative colitis patients with persistent symptoms despite tacrolimus therapy. Methods: We report a retrospective, observational, single‐center case series of 12 consecutively enrolled patients with ulcerative colitis refractory to tacrolimus that received infliximab therapy for the induction of remission. Eight patients received a single infusion of infliximab, and four received two or more infusions. Median follow‐up duration was 16.0 months (range, 1.6–41.4 months). The clinical response was evaluated based on a modified Truelove‐Witts severity index. Results: Six patients (50.0%) achieved clinical remission within 30 days. Overall cumulative colectomy‐free survival was estimated to be 58.3% at 41.4 months. Adverse events included an elevation of liver enzymes (1/12; 8.3%) and a mild infusion reaction (1/12; 8.3%). No mortality occurred. Conclusions: Infliximab can induce remission in patients with ulcerative colitis who do not tolerate or respond to tacrolimus therapy.