Tailored treatment options for patients with psoriatic arthritis and psoriasis: review of established and new biologic and small molecule therapies

The diverse clinical picture of PsA suggests the need to identify suitable therapies to address the different combinations of clinical manifestations. This review aimed to classify the available biologic agents and new small molecule inhibitors (licensed and nonlicensed) based on their proven efficacy in treating different clinical manifestations associated with psoriasis and PsA. This review presents the level of evidence of efficacy of different biologic treatments and small molecule inhibitors for certain clinical features of treatment of PsA and psoriasis, which was graded in categories I–IV. The literature searches were performed on the following classes of biologic agents and small molecules: TNF inhibitors (adalimumab, etanercept, infliximab, golimumab, certolizumab), anti-IL12/IL23 (ustekinumab), anti-IL17 (secukinumab, brodalumab, ixekizumab), anti-IL6 (tocilizumab), T cell modulators (alefacept, efalizumab, abatacept, itolizumab), B cell depletion therapy (rituximab), phosphodiesterase 4 inhibitor (apremilast) and Janus kinase inhibitor (tofacitinib). A comprehensive table including 17 different biologic agents and small molecule inhibitors previously tested in psoriasis and PsA was generated, including the level of evidence of their efficacy for each of the clinical features included in our review (axial and peripheral arthritis, enthesitis, dactylitis, and nail and skin disease). We also proposed a limited set of recommendations for a sequential biologic treatment algorithm for patients with PsA who failed the first anti-TNF therapy, based on the available literature data. There is good evidence that many of the biologic treatments initially tested in psoriasis are also effective in PsA. Further research into both prognostic biomarkers and patient stratification is required to allow clinicians the possibility to make better use of the various biologic treatment options available. This review showed that there are many potentially new treatments that are not included in the current guidelines that can be used for selected categories of patients based on their disease phenotype, clinician experience and access to new biologic therapies

Established and new biologic therapies for psoriatic arthritis and psoriasis

Psoriatic arthritis (PsA) is part of the group of seronegative spondyloarthropathies (SpA). These diseases share common clinical features such as sacroiliitis, spondylitis, enthesitis, psoriasis, uveitis, and genetic markers. The newly developed biologic treatments aim to target molecular and cellular abnormalities associated with autoimmunity in PsA and psoriasis. There are several biologic agents which are currently used, or are under investigation in both diseases, which creates an opportunity for rheumatologists and dermatologists to share their expertise for patients’ benefit. Apart from the large body of evidence for efficacy of the licensed biologic therapies in psoriasis and PsA, research efforts are currently put into discovering and testing new molecular targets with therapeutic potential. This chapter will review all the biologic agents ever tested in these two diseases, stratified based on the level of evidence regarding their efficacy. As PsA and psoriasis have a diverse clinical phenotype, it is useful to identify which treatments are effective for a particular clinical manifestation, such as axial and peripheral arthritis, dactylitis, enthesitis, skin and nail disease. Another aspect of biologic treatment effectiveness that will be explored in this chapter is the impact of these agents on patients’ quality of life and functional ability. We propose that by analysing the patient’s individual disease phenotype, based on clinical assessments and biomarkers, there is a huge opportunity to optimise the cost-effectiveness of biologic treatments, by facilitating tailored treatment options for patients with PsA and psoriasis

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Thigh-length compression stockings and DVT after stroke

Controversy exists as to whether neoadjuvant chemotherapy improves survival in patients with invasive bladder cancer, despite randomised controlled trials of more than 3000 patients. We undertook a systematic review and meta-analysis to assess the effect of such treatment on survival in patients with this disease

Current concepts and unmet needs in psoriatic arthritis

Psoriatic arthritis is a chronic inflammatory arthritis that is part of the spondyloarthropathy group of rheumatic diseases and has associated co-morbidities. It can present with various clinical manifestations making diagnosis and treatment challenging, resulting in significant disability and reduced quality of life for patients. Whilst there have been advances in understanding the pathogenic mechanisms of the disease which have resulted in targeted therapies, there is still the need for further studies as some patients fail or are intolerant of current therapies. Better identification of early disease and knowledge of prognostic markers would enable clinicians to initiate appropriate therapy with the expectation that early aggressive treatment will minimise joint damage progression. Improved knowledge of the condition would also enable clinicians to better tailor specific treatment strategies for each of the various clinical domains in psoriatic arthritis