over the past decade , biologic therapies against tnf- , il-17 , and il-12/il-23 have revolutionized the treatment of chronic inflammatory diseases including psoriasis . although these medications have demonstrated favorable efficacy and side effect profiles , a subset of patients fails to respond and others lose response over time . even patients who have treatment success often desire to escalate their dose ( langley et al . , 2015 ) . the prevalence of non - responders , defined as the failure to achieve a 75% reduction in psoriasis area and severity index ( pasi ) scores by week 12 - 16 of therapy , ranged from 51 - 66% for etanercept ( papp et al . , 2005 , tyring et al . , 2006 ) , 20 - 32% for adalimumab ( menter et al . , 2008 , thai et al . , 2010 ) , 24 - 34% for ustekinumab ( leonardi et al . , 2008 , papp et al . , 2008 ) , 18 - 33% for secukinumab ( langley et al . , 2014 ) , and 11 - 19% for ixekizumab ( gordon et al . , 2016 ) in phase iii clinical trials . when treating a patient who has failed to respond to biologic therapy , which in the united states has usually been preceded by systemic medications per insurers appropriateness criteria , clinicians must decide between dose escalation , switching biologics , and adding or switching to a non - biologic systemic drug or phototherapy . in this era of renewed focus on cost and quality , this decision becomes increasingly important , especially because psoriasis patients may be taking these drugs for several decades . although dose escalation is perhaps the simplest strategy and has been shown to be well - tolerated in the majority of patients , even when outside labeling by the u.s . food and drug administration ( fda ; brezinski and armstrong , 2012 ) , it confers a tremendous cost burden because doubling the dosage also doubles the wholesale price ( redbook online ) . for example , the maintenance dose of etanercept is 50 mg weekly ( papp et al . , 2005 , tyring et al . , 2006 ) , which costs approximately $ 53,909 per year in the united states . increasing the dose to 50 mg transitioning to another biologic , such as adalimumab or ustekinumab , is a far more cost - effective strategy with an annual cost that is approximately equivalent ( redbook online ; table 1 ) . this issue is further complicated by the weight - based dosing of ustekinumab . for patients who weigh   100 kg , the maintenance dose is 45 mg every 12 weeks ( a cost of $ 39,311 per year ) , which can later be escalated to 90 mg every 12 weeks if necessary ( a cost of $ 78,622 per year ) . patients who weigh more than 100 kg , however , initiate the higher dose from the beginning . escalating to 90 mg every 8 weeks may improve efficacy in these patients , however , this dose is not fda - approved and costs approximately $ 117,933 per year ( leonardi et al . , 2008 , papp et al . all patients are initiated on 300 mg weekly for 5 weeks , followed by 300 mg every 4 weeks , which may later be decreased to 150 mg every 4 weeks in some patients . the annual cost of maintenance therapy for patients who remain on the 300 mg dose is approximately $ 57,033 . although this is one of the more expensive options , there is at least the reassurance that the cost will not double in the future due to dose escalation . in addition , the annual cost for patients who maintain the 150 mg dose is only $ 28,517 , because even though the 150 mg and 300 mg dose packages are the same price , patients could theoretically get around this by purchasing the 300 mg package and administering the contents as two separate 150 mg doses ( langley et al . , 2014 , these considerations could lead to treatment algorithms designed to mimimize costs , which favor switching biologics over dose escalation ( figure 1 ) . unfortunately , although this is more affordable , there are potential clinical consequences such as the development of anti - drug antibodies ( hsu and armstrong , 2013 ) , which can limit a patient s future treatment options . switching to a biosimilar will also become an option in the future as these drugs emerge on the market . unfortunately , they are only expected to decrease costs by 20 - 40% ( rumore and vogenberg , 2016 ) , and their long - term safety and efficacy have yet to be determined . another option is to add or switch to a systemic medication such as methotrexate , which carries the risk of cumulative toxicity ( cather and crowley , 2014 ) . starting methotrexate at the time of biologic initiation may also improve response and prevent the need for dose escalation later on , however clinicians should keep in mind the trade - off between any potential cost reduction and the safety profile of methotrexate . in this era of increasingly hard choices biologic drugs are expensive to develop , and the united states subsidizes these drugs for the rest of the world , making it an immense challenge to control prices . however , some patients may be best served by dose escalation , and we need to maintain affordability . dose escalation may actually be cheaper because of negotiated pricing , but it is difficult for physicians and even health care systems to get access to this data . in conclusion , biologics have demonstrated great success in the treatment of psoriasis , but carry with them a substantial cost burden . this is especially true for patients who fail to respond to starting doses , because dose escalation typically doubles the price of the medication . as a result , clinicians may be compelled to switch to a different biologic without first attempting to increase the dose . moving forward , our field should support efforts to develop rational strategies for the pricing of dose escalation in order to minimize this phenomenon . these strategies would be substantially improved as well if there were increased transparency surrounding negotiated pricing , which would help ensure that all patients have access to the most effective , affordable treatment options available .
although biologic medications have demonstrated great efficacy for the treatment of psoriasis , a subset of patients fails to respond and others lose response later in the course . in treating a patient who has failed to respond to biologic therapy 
 , clinicians must decide between dose escalation , switching biologics , and adding or switching to a non - biologic systemic drug or phototherapy . 
 although dose escalation is perhaps the simplest strategy and generally well - tolerated , it confers a tremendous cost burden because doubling the dosage is likely to double the wholesale price . 
 we call for the development of rational strategies for the pricing of dose escalation in order to minimize this phenomenon 
 . we also call for increased transparency surrounding negotiated pricing to ensure that all patients have access to the most effective , affordable treatment options available .