Biological therapies in the treatment of inflammatory disease and cancer: impact on pulmonary infection.

Biological therapies are increasingly used for the treatment of inflammatory conditions in the realms of rheumatology, dermatology, and gastroenterology due to their ability to target specific cytokines in the inflammatory cascade. The impact of these biologic therapies is immunosuppression leading to an increased risk of infection. This review focuses on commonly used biologic agents in the treatment of inflammatory conditions and cancer and their impact on pulmonary infections. We have summarized potential pathogens in this group of patients. The hope being that this will increase awareness and therefore prevention timely diagnosis and successful treatment of patients receiving biologic therapies. It is also important to note that it is not solely the choice of an agent that predisposes to particular infections. Concomitant factors that might increase an individuals' risk of contracting an infection include the underlying disease, comorbid diseases, increased age, and other medical treatment as well as exposure to opportunistic pathogens. In the treatment of cancers many immunotherapies are being developed. The most notable adverse effects from immunotherapy are due to stimulation of the immune response, and these may mimic infection by causing flu-like symptoms and breathlessness due to pneumonitis. The treatment of this is immunosuppression, further leading to an increased risk of infection. Biologic therapies have been a revolution in the treatment of inflammatory conditions and cancers. They have improved outcomes and quality of life for patients. However, the use of these drugs needs to be balanced against the risk of infection and every patient needs to be assessed on an individual basis

Biologic therapies for systemic lupus erythematosus: where are we now?

Advances in molecular biology have led to the development of biologic therapies. This is particularly relevant in systemic lupus erythematosus (SLE), which is a multisystem autoimmune rheumatic disease (ARD) associated with potentially life-threatening complications if not adequately treated. The availability of new biologic drugs has improved the prognosis of SLE in selected cases associated with unsatisfactory response to conventional therapies. Over the last decade, there have been developments in the availability of biologic agents for SLE treatment based upon the advances in the understanding of the disease pathogenesis. Even if the evidence of biologic treatment efficacy in SLE is weaker than in other autoimmune rheumatic diseases, such as rheumatoid arthritis (RA), significant progress was made, as the first biologic treatment for use in SLE patients received approval in 2011. These new biologic therapies for SLE range from anti-CD20/CD22 (clusters of differentiation characteristic to B cells), to anti-B cell activating factors and anti-interferon alpha (IFNα). This chapter reviews the various biologic agents used in SLE, their mechanism of action and safety profile. The most common side effects to biologic treatments include infection, tuberculosis (TB) reactivation and allergic reactions. Less common side effects include development of lymphoma and anti-drug or autoimmune antibody formation. Despite their toxicity profile, biologic agents are gaining ground in clinical practice due to the limited efficacy or increased toxicity of conventional disease modifying agents (DMARD’s). Biologic therapies targeting B cells, such as rituximab, and B cell activation factors, such as belimumab, are currently used in the treatment of refractory SLE. Furthermore, aggressive treatment, including the use of biologic agents, reduces long-term complications associated with prolonged use of steroids in SLE, such as cardiovascular disease and osteoporosis. In the short term, the biologic agents are expensive when compared to traditional DMARDs; however there is evidence that their use is associated with long term benefits for patients with SLE, such as reduced hospital admission and disease complications, and improved patient outcomes. This chapter provides a summary of most biologic agents tested in SLE patients, considering their efficacy and safety profile, as well as the health implications associated with their use. We also take a brief look at newer agents currently investigated in clinical trials

Hypovitaminosis D among rheumatology outpatients in clinical practice.

OBJECTIVES: A role for vitamin D in the pathogenesis of autoimmune and inflammatory diseases is emerging. We undertook an audit of 25-hydroxyvitamin D (25OHD) investigation and treatment in rheumatology outpatients. METHODS: Serum 25OHD requests were matched to electronic medical records from rheumatology and metabolic bone clinics (April 2006-March 2007). Data were analysed separately for two groups, 'Documented osteoporosis/osteopaenia' (Group 1) and 'General rheumatology outpatients' (Group 2, sub-divided by diagnosis). Hypovitaminosis D was defined by 25OHD levels <50 nmol/l. Values were compared with healthy adults to calculate geometric z-scores. RESULTS: A total of 263 patients were included (Group 1, n = 122; Group 2, n = 141) with an overall median 25OHD of 44 nmol/l. The 25OHD level among general rheumatology patients (median 39 nmol/l, mean z score -1.2, was statistically significantly lower than among osteoporotic/osteopaenic patients (median 49 nmol/l, mean z score of -0.9, p < 0.05 for the difference). 25OHD was lower in inflammatory arthritis and chronic pain/fibromyalgia than in other groups. Prescribing was recorded in 100 in Group 1 (of whom 95% were prescribed calcium/800 IU cholecalciferol) and 83 in Group 2 (91% calcium/800 IU). Only 31% of the patients with 25OHD <50 nmol/l would have been identified using general guidelines for screening patients at 'high risk' of hypovitaminosis D. CONCLUSIONS: Improved guidelines for managing hypovitaminosis D in rheumatology patients are needed. We found a high prevalence of hypovitaminosis D among secondary care patients in rheumatology and widespread supplementation with 800 IU cholecalciferol. Substantially reduced levels of serum 25OHD were identified among patients with inflammatory arthritis and chronic pain

Clinical features of rheumatoid arthritis

Rheumatoid arthritis (RA) is a multiorgan chronic inflammatory condition that affects >430,000 people in the UK, constituting approximately 0.84% of the UK population. The cardinal clinical feature is a symmetrical polyarthritis that predominantly affects the small joints. RA can affect other components of the musculoskeletal system (bursitis, tendinopathy, muscle atrophy, osteoporosis) and almost every organ in the body. Extra-articular manifestations of RA can be cutaneous, haematological, neurological, pulmonary, cardiac, renal and ocular. A better understanding of the varied clinical aspects of RA is vital to instigating appropriate management. This review provides a detailed description of the clinical manifestations of RA, both musculoskeletal and extra-articular

Safety of anti-rheumatic drugs in men trying to conceive: A systematic review and analysis of published evidence

There is limited evidence relating to the impact of disease modifying anti-rheumatic drugs (DMARDs) upon male fertility and peri-conception paternal exposure in men with rheumatic disease. Therefore, we conducted a systematic review of available evidence to update information on this subject and guide paternal counselling. A systematic search of PubMed and Embase was carried out up to September 2017, to find relevant peer-reviewed papers, using keywords for fertility/spermatogenesis/conception, men, and disease modifying or biologic drugs commonly prescribed in patients with rheumatic disease. The search yielded 724 papers, and the titles/abstracts were screened independently by 2 authors, duplicates removed and 233 potentially relevant papers selected for full text review. A total of 84 papers were included in the final analysis which covered the impact on fertility of over 611 male exposures to relevant drugs, and over 5986 pregnancies conceived during paternal exposure to (or within 3 months of stopping) these drugs. Aside from the known adverse impact of cyclophosphamide and sulfasalazine on spermatogenesis, overall there was no firm evidence of harm to fertility or pregnancy outcomes with paternal exposure to anti-TNF therapies, abatacept, rituximab, azathioprine, cyclosporine A, hydroxychloroquine, leflunomide, methotrexate or mycophenolate mofetil. There was no evidence found pertaining to the effects of male exposure to IVIG, tacrolimus, golimumab, anakinra or belimumab on fertility or pregnancy outcomes. These results provide further reassurance as to the safety of many DMARDs for men trying to conceive and will be useful when counselling men about risks of anti-rheumatic drugs to fertility and pregnancies, and following accidental conception

Animation-supported consent for urgent angiography and angioplasty: a service improvement initiative.

OBJECTIVE: Patient understanding of angiography and angioplasty is often incomplete at the time of consent. Language barriers and time constraints are significant obstacles, particularly in the urgent setting. We introduced digital animations to support consent and assessed the effect on patient understanding. METHODS: Multi-language animations explaining angiography and angioplasty (www.explainmyprocedure.com/heart) were introduced at nine district hospitals for patients with acute coronary syndrome before urgent transfer to a cardiac centre for their procedure. Reported understanding of the reason for transfer, the procedure, its benefits and risks in 100 consecutive patients were recorded before introduction of the animations into practice (no animation group) and in 100 consecutive patients after their introduction (animation group). Patient understanding in the two groups was compared. RESULTS: Following introduction, 83/100 patients reported they had watched the animation before inter-hospital transfer (3 declined and 14 were overlooked). The proportions of patients who understood the reason for transfer, the procedure, its benefits and risks in the no animation group were 58%, 38%, 25% and 7% and in the animation group, 85%, 81%, 73% and 61%, respectively. The relative improvement (ratio of proportions) was 1.5 (95% CI 1.2 to 1.8), 2.1 (1.6 to 2.8), 2.9 (2.0 to 4.2) and 8.7 (4.2 to 18.1), respectively (p<0.001 for all comparisons). CONCLUSION: Use of animations explaining angiography and angioplasty is feasible before urgent inter-hospital transfer and was associated with substantial improvement in reported understanding of the procedure, its risks and its benefits. The approach is not limited to cardiology and has the potential to be applied to all specialties in medicine