Adalimumab: a review of side effects

Adalimumab (Humira^®) is a human monoclonal TNF-α antibody that blocks the effects of TNF-α. It is administered by subcutaneous injection. It has been approved alone or in combination with methotrexate for the treatment of rheumatoid arthritis in the EU and US. Approval for its use for the treatment of psoriasis, psoriatic arthritis and ankylosing spondylitis is expected in the near future. Its side effect profile is favourable when compared with traditional systemic treatments for these diseases. It does not require laboratory monitoring. The most common side effects of adalimumab are injection site reactions. Adalimumab increases the risk of rare serious infections. There is a two-fold risk of serious infections with the use of adalimumab, as reported in the Premier trial. This risk should not be minimised in this way. It should not be used during periods of active infection. Its most notable infectious complication is the reactivation of tuberculosis. Tuberculosis screening should be according to country standards and may or may not include purified protein derivative test or chest X-ray. Deep fungal and other serious and atypical infection can also be promoted by adalimumab. It has been associated infrequently with skin rashes. Rare side effects include: worsening or initiation of congestive heart failure, a lupus-like syndrome, a promotion of lymphoma, medically significant cytopenias, and worsening or initiation of a multiple sclerosis/neurological disease. There has been reported pancytopenia and elevated transamines with the use of adalimumab, which suggest that laboratory monitoring blood counts and liver functions, at least intermittently, are useful. In patients with any of the foregoing problems, its use should be extremely carefully considered. Adalimumab is a useful medication which can be safely used if its side effects are recognised.     

Infliximab for the treatment of psoriasis

Psoriasis is a common immune-mediated skin disease producing significant morbidity. Tumour necrosis factor (TNF)-α, a pro-inflammatory cytokine, plays a key role in the cutaneous inflammation characteristic of psoriasis. Infliximab is a chimeric monoclonal antibody that specifically binds to TNF-α, thereby blocking its biological activity. Data from Phase II and III studies indicate that infliximab is a highly effective, rapidly acting systemic therapy for patients with moderate-to-severe psoriasis. Regular 8-weekly infusions of infliximab maintain significant clinical improvement in the majority of patients for at least 1 year. Infliximab is generally well tolerated, but patients may be susceptible to infection and malignancy.     

Ultrasound in gastroenterology

Crohn’s disease (CD) is an inflammatory bowel disease whose precise etiology is still unknown, and therefore a causal therapy is not yet available. Studies showing the overexpression of IL-12 and IL-23, polymorphisms in genes encoding those cytokines and their receptors and genome-wide association studies have linked Crohn’s pathogenesis with IL-12/23 pathway. Ustekinumab is a novel therapeutic IgG₁ kappa monoclonal antibody that modulates Th1 and Th17 function, by blocking the p40 subunit of both IL-12 and IL-23 and preventing the interaction with their receptors on T cells, natural killer cells and antigen-presenting cells with established efficacy in psoriasis. This review will mainly focus on the available evidence on the role of ustekinumab in moderate-to-severe CD. The potential role of this biologic in the armamentarium of CD therapy is discussed.     

Quality Of Life of Patients with Neurodermatitis

Background: Neurodermatitis is a common chronic skin disease. Although not life-threatening, it can produce an important psychosocial burden, sleep disturbance and sexual dysfunction. Patients with neurodermatitis tend to have poor social skills or interpersonal resources and a lack of flexibility. However quality of life (QoL) of patients with neurodermatitis has seldom investigated. The objective of this study is to assess the impact of neurodermatitis on patients'' QoL using the Dermatology Life Quality Index questionnaire, and assess its feasibility and internal consistency.Methods: One hundred and fifty consecutive outpatients seeking treatment for neurodermatitis and 250 patients with psoriasis in the Department of Dermatology, the Second Hospital of Xi''an Jiaotong University, were assessed for eligibility for this prospective study from July 1, 2011 to September 30, 2011. Demographic data and disease-related characteristics were collected.Results: The overall mean DLQI score for neurodermatits (9.34) was lower than that for psoriasis (13.32) (P < 0.001). Patients with neurodermatitis scored significantly lower for all items except Q1 (symptoms) and Q9 (sexual difficulties). No strong relationship between disease-related characteristics and quality of life could be found. The inter-item correlation averaged 0.415 and Cronbach''s alpha was 0.889, indicating high internal consistency.Conclusion: This is the first study to attempt to measure the impact of neurodermatitis for both male and female patients on QoL. Neurodermatitis moderately affected the QoL of the patients.     

Tumor necrosis factor-alpha antagonist therapy-induced psoriasis in Turkey: analysis of 514 patients

Abstract

Objectives New adverse events are being reported with the increased use of anti-tumor necrosis factor (TNF) α therapy. We studied cases of anti-TNFα-induced psoriasis observed in our pool of 514 patients receiving anti-TNFα treatment in Turkey.

Methods Three rheumatoid arthritis patients and 3 ankylosing spondylitis patients with anti-TNFα-induced psoriasis were included in the study. All patients were examined by a dermatologist, and 3 patients underwent skin biopsy.

Results None of the 6 patients had preexisting psoriasis or a familial history of psoriasis. The earliest and latest occurrences of psoriatic lesions were at the 6th week and 44th month of anti-TNFα therapy, respectively. Psoriasis was severe and refractory in two patients (requiring systemic treatment), while it presented as mild in four patients. Anti-TNFα therapy was totally withdrawn in case 1. In case 2, the treatment was halted for 3 months then switched to another TNFα blocker, and case 3 was switched to another anti-TNFα treatment. The treatment was sustained in the other 3 patients (cases 4, 5, and 6).

Conclusions TNFα blockers are very effective agents in the treatment of psoriasis, but it is interesting that the same molecules can, paradoxically, induce psoriasis. The occurrence of anti-TNFα-induced psoriasis in six out of 514 patients suggests that the incidence of this adverse reaction is, in fact, as not low as presumed in the literature. In some cases, a severe course of psoriasis may limit the use of these agents.     

Drug survival rates in patients with psoriasis after treatment with biologics

Clinically, patients' adherence to biologic treatment is not only related to efficacy but also to adverse events, cost and other factors. To evaluate long‐term viability of biologic treatment, both the percentage of and reasons for discontinuation of treatment were investigated. In this study, patients treated with infliximab (n = 38), adalimumab (n = 59) and ustekinumab (n = 30) were included and observed for 12 months. Clinical efficacy was evaluated using a 75% reduction of Psoriasis Area and Severity Index score (PASI‐75), and patients who discontinued treatment were considered as not having achieved PASI‐75. In addition, drug survival rate (DSR) was investigated. In patients treated with infliximab, PASI‐75 was 68.4% and DSR was 73.3% by the end of treatment. In patients treated with adalimumab, PASI‐75 was 50.8% and DSR was 79.7%. In patients treated with ustekinumab, PASI‐75 was 63.3% and DSR was 96.7%. Several patients discontinued treatment because of insufficient efficacy due to secondary failure in infliximab or primary failure in adalimumab. To increase treatment efficacy, it will be necessary for these patients to use an additional concomitant treatment. Higher efficacy is expected with biologics than with conventional treatments; however, the actual clinical efficacy over a long period of time may be insufficient if they are used without any concomitant treatments.