Biosimilars: From Extrapolation into Off Label Use

Zhao, Sizheng Steven; Nair, Jagdish; Moots, Robert J.

doi:10.2174/1381612824666171129193258

Cited by 6 publications

(3 citation statements)

References 44 publications

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“…Weighing economic implications vs. health improvement will remain a difficult balance in the next decades. The rise of biosimilars may improve access to off-label use in disorders which are unlikely to be of economic interest due to their rare incidence or limited patients with severe disease requiring biologics (109). An increased appreciation and funding of investigator-initiated clinical trials seem of particular relevance to explore the full capacity of biologics.…”

Section: Discussionmentioning

confidence: 99%

Learning From Success and Failure: Biologics for Non-approved Skin Diseases

2019

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The impressive potential of biologics has been demonstrated in psoriasis, hidradenitis suppurativa, and urticaria. Numerous biologicals are entering the field for a restricted number of skin disorders. Off-label use of biologics in other recalcitrant skin diseases has increased. Mounting data point to the potential of already existing biologics acting on the IL-17/IL-23 pathway in skin disorders with epidermal hyperkeratosis (e.g., pityriasis rubra pilaris), acneiform inflammation (e.g., hidradenitis suppurativa), and loss of mucosal integrity (e.g., aphthosis). TNF-α blockers are also effective in the latter conditions but seem of particular value in granulomatous (e.g., granuloma annulare) and neutrophilic disorders (e.g., pyoderma gangrenosum). Failure of IL-17 blockade in skin diseases resulting from immune-mediated cell destruction (e.g., alopecia areata and vitiligo) illustrates its limited involvement in Th1-dependent skin immunology. Overall, disappointing results of TNF-α blockers in alopecia areata and vitiligo point to the same conclusion although promising results in toxic epidermal necrolysis suggest TNF-α exerts at least some in vivo Th1-related activities. Acting on both the Th1 and Th17 pathway, ustekinumab has a rather broad potential with interesting results in lupus and alopecia areata. The efficacy of omalizumab in bullous pemphigoid has revealed an IgE-mediated recruitment of eosinophils leading to bullae formation. Reconsidering reimbursement criteria for less common but severe diseases seems appropriate if substantial evidence is available (e.g., pityriasis rubra pilaris). For other disorders, investigator-and industry-initiated randomized clinical trials should be stimulated. They are likely to improve patient outcome and advance our understanding of challenging skin disorders.

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Section: Discussionmentioning

confidence: 99%

Learning From Success and Failure: Biologics for Non-approved Skin Diseases

2019

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“…Etanercept [ 2 ] and infliximab, inhibitors of proinflammatory cytokine tumor necrosis factor alpha (anti-TNF) [ 3 ], were the first anti-TNF biological drugs indicated for rheumatoid arthritis, and later more biological drugs against TNFα were developed, including adalimumab [ 4 ], certulizumab pegol [ 5 ] and golimumab [ 6 ]. In recent years, the emergence of biosimilars of anti-TNF biological drugs has also somewhat reduced the initially high cost of anti-TNF therapy while maintaining efficacy levels comparable to those of the originator biological drugs [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Gene Ontology Analysis Highlights Biological Processes Influencing Non-Response to Anti-TNF Therapy in Rheumatoid Arthritis

2022

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Anti-TNF therapy has significantly improved disease control in rheumatoid arthritis, but a fraction of rheumatoid arthritis patients do not respond to anti-TNF therapy or lose response over time. Moreover, the mechanisms underlying non-response to anti-TNF therapy remain largely unknown. To date, many single biomarkers of response to anti-TNF therapy have been published but they have not yet been analyzed as a system of interacting nodes. The aim of our study is to systematically elucidate the biological processes underlying non-response to anti-TNF therapy in rheumatoid arthritis using the gene ontologies of previously published predictive biomarkers. Gene networks were constructed based on published biomarkers and then enriched gene ontology terms were elucidated in subgroups using gene ontology software tools. Our results highlight the novel role of proteasome-mediated protein catabolic processes (p = 2.91 × 10−15) and plasma lipoproteins (p = 4.55 × 10−11) in anti-TNF therapy response. The results of our gene ontology analysis help elucidate the biological processes underlying non-response to anti-TNF therapy in rheumatoid arthritis and encourage further study of the highlighted processes.

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“…Furthermore, certain off-label uses of medicines are integral to disease treatment and are recommended in guidelines. 14 The off-label use of generic drugs is quite common as a rare disease solution. 15 , 16 Therefore, the rate of off-label drug prescribing will likely continue to increase.…”

Section: Introductionmentioning

confidence: 99%