Experience with anti‐tumor necrosis factor‐α therapy in India

Aims: To review the Indian experience with anti‐tumor necrosis factor (TNF)‐α therapy. Methods: ‘PubMed’ and ‘IndMED’ were searched for Indian studies on anti‐TNF‐α therapy. Data were compiled and analysed. Results: Data on infliximab from 176 patients from five different series were collated. One hundred and forty‐seven had ankylosing spondylitis (AS), nine had polyarticular juvenile idiopathic arthritis (JIA), 12 had rheumatoid arthritis (RA), six had undifferentiated spondyloarthropathy, one had inflammatory bowel disease‐related spondyloarthritis and one had psoriatic arthritis. Thus, 155/176. (88%) had spondyloarthropathy (SpA). No screening for latent tuberculosis was done in any of the studies. One series comprising 108 cases of AS, used 3 mg/kg infliximab infusions (instead of 5 mg/kg) at 8‐weekly intervals with omission of the 2‐week and 6‐week doses. All others with SpA (n = 47) followed the standard protocol: 171/176 patients had a significant improvement. Reactivation tuberculosis developed in 5/47 (10.6%) SpA patients treated with standard doses of infliximab. This amounted to 56 times increased risk compared to baseline (0.187%). None of the 129 patients treated with 3 mg/kg infusions of infliximab developed reactivation tuberculosis (AS ?108, RA ?12, JIA ?9). The lone study on etanercept showed good efficacy in 40 patients with RA. However, seven serious adverse events occurred. Conclusions: Infliximab showed expected efficacy in SpA, RA and JIA. Reactivation tuberculosis developed in 10.6% of the SpA group treated with standard regimen. Patients treated with lower doses of infliximab which included a large subgroup of SpA patients and those with RA or JIA did not develop tuberculosis.     

Risk of tuberculosis in a Chinese registry of rheumatoid arthritis and ankylosing spondylitis for tumour necrosis factor‐α antagonists

Aim: To understand the risk of tuberculosis (TB) infection in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) who required tumour necrosis factor‐α (TNF‐α) antagonist treatment. Methods: Patients with RA and AS who were screened for infliximab and etanercept treatment for up to 6 months were entered in a registry between 2003 and 2005. The purified protein derivative (PPD) test and chest anteroposterior and lateral view X‐ray were performed at screening. The risk of TB infection in theses patients was observed during follow up. Results: Among 67 RA patients screened, a positive PPD reaction was found in one patient. Of the 169 AS patients screened, 23 were positive for the PPD reaction, two had pulmonary TB calcinosis and two were diagnosed as having pulmonary TB. The incidence of PPD positive reaction and pulmonary TB calcinosis or active TB in our screened RA and AS patients was significantly lower than that reported in the recent fourth national TB infection rates and prevalence (P < 0.01). Only one patient with RA developed neck lymph node TB 6 months after completion of infliximab infusion. Conclusion: Patients with AS and RA are not at an increased risk of TB infection if screened properly before short course treatment with anti‐TNF‐α agents.     

‘It's magic stuff’: The experiences of patients with ankylosing spondylitis taking anti‐TNF‐α medication

Introduction: Several studies have identified the efficacy of anti‐tumour necrosis factor‐alpha (anti‐TNF‐α) treatment in ankylosing spondylitis (AS). However, few studies have explored the perceptions of patients taking this new medication. The aim of this study was to explore the impact of anti‐TNF‐α on the quality of life of people with AS. Methods: A qualitative approach was adopted to provide a holistic understanding of participants' views and experiences in the context of their overall lives. Semi‐structured interviews were undertaken and transcribed verbatim. Data were analysed using thematic analysis. Ethical approval and informed consent were obtained. Results: Eight people participated and described a significant improvement in their physical and psychological status, leading to a more positive outlook on their life. Specific areas highlighted were employment, activities of daily living, hobbies and relationships with partners and family, some of which are not captured by current AS‐specific outcome measures. Negative aspects of anti‐TNF‐α use were described as the inconvenience of monitoring and issues relating to travelling abroad. All participants expressed concern about the possibility of being withdrawn from treatment and the perceived impact this would have on their lives. Conclusions: Anti‐TNF‐α treatment has a positive impact on the lives of people with AS, such that a major concern is being withdrawn from treatment, highlighting the need to provide tailored support to people being withdrawn from treatment. To capture the full impact of anti‐TNF‐α treatment, further consideration needs to be given to the choice of appropriate outcome measures. Copyright © 2008 John Wiley & Sons, Ltd.     

Melatonin attenuates TNF‐α and IL‐1β expression in synovial fibroblasts and diminishes cartilage degradation: Implications for the treatment of rheumatoid arthritis

The hormone melatonin has many properties, including antioxidant, anti‐inflammatory, and immunomodulatory effects. Melatonin has been demonstrated to be beneficial in several inflammatory autoimmune diseases, but its effects in rheumatoid arthritis (RA) remain controversial. We sought to determine how melatonin regulates inflammation in RA. We found that melatonin dose‐dependently inhibits tumor necrosis factor‐α (TNF‐α) and interleukin (IL)‐1β expression through the PI3K/AKT, ERK, and NF‐κB signaling pathways. We also identified that melatonin inhibits TNF‐α and IL‐1β production by upregulating miR‐3150a‐3p expression. Synovial tissue specimens from RA patients and culture of human rheumatoid fibroblast‐like synoviocytes confirmed that the MT1 receptor is needed for the anti‐inflammatory activities of melatonin. Importantly, melatonin also significantly reduced paw swelling, cartilage degradation, and bone erosion in the collagen‐induced arthritis mouse model. Our results indicate that melatonin ameliorates RA by inhibiting TNF‐α and IL‐1β production through downregulation of the PI3K/AKT, ERK, NF‐κB signaling pathways, as well as miR‐3150a‐3p overexpression. The role of melatonin as an adjuvant treatment in patients with RA deserves further clinical studies.     

Chronic necrotizing pulmonary aspergillosis in a patient treated with a tumor necrosis factor‐α inhibitor

Tumor necrosis factor (TNF)‐α is a pro‐inflammatory cytokine that plays an important role in the pathogenesis of a variety of autoimmune diseases. TNF‐α inhibitors have been shown to offer clinical benefits in the treatment of autoimmune and inflammatory disorders, including rheumatoid arthritis, ankylosing spondylitis (AS), and Crohn’s disease. Occasionally, these agents have been associated with infectious complications because of their immunosuppressive activity. Globally, several cases of infections associated with TNF‐α inhibitors have been reported. However, Aspergillus infection associated with etanercept is very rare. We report a case of chronic necrotizing pulmonary aspergillosis in a 51‐year‐old man with AS that developed after treatment with etanercept.