that when a prescription is written for a biologic in a patient with psoriasis, 30-50% of patients will not receive a second prescription for that medication. There are many reasons for the lack of a second prescription including patients not initiating therapy, discontinuation for side effects and lack of, or suboptimal, insurance coverage. All these factors contribute to the difficulty that providers have selecting appropriate systemic treatments for patients with psoriasis.
Additionally, we also found a high percentage of concurrent methotrexate and topical steroid use in patients receiving prescriptions or biologic therapies, and use continued to be high, even after excluding the first 3 months after initiation of a biologic, suggesting ongoing use. Concomitant oral therapy use is consistent with what has been previously reported in the literature. Data from PSONET, a prospective network of psoriasis registries from Europe, found that 9.9% of biologic treatment cycles involved combination with a systemic therapy.11 Of these treatment cycles with combination therapy, 72.9% involved methotrexate, 25.3% involved UVB phototherapy, acitretin or cyclosporine and 1.8% involved PUVA, fumaric acids or a second biologic.11 HMO data from Israel showed that 7.1% of patients on adalimumab, 16.2% of patients on etanercept, 19.7% of patients on infliximab and 8% of patients on ustekinumab were taking methotrexate concomitantly, and 2.7% of patients on adalimumab, 2.2 % on etanercept, and 5.8% on ustekinumab were taking concomitant acitretin.12 Less than 1% of patients in each biologic group were taking cyclosporine, which is similar to what is reported in this study.
Previous research has suggested a benefit from the co-administration of methotrexate with biologics. Treatment guidelines from the medical board of the National Psoriasis Foundation report that combination treatment with etanercept and methotrexate or infliximab and methotrexate is more effective than monotherapy with either TNF inhibitor or methotrexate alone.13 Additionally, in drug survival analyses, methotrexate has been associated with in increased risk of drug survival.3,12 There are many reasons why a provider may prescribe concomitant methotrexate including loss of efficacy of the primary therapy, prevention of anti-drug antibodies and to enhance treatment effect in patients with psoriatic arthritis. With the advent of new, more efficacious biologic medications for psoriasis, continued research is necessary to understand the risk and benefits of concurrent methotrexate with newer drugs.
Guidelines also recommend that topical therapies are used as adjunctive therapy for patients with extensive psoriasis undergoing systemic therapy with phototherapy or biologics,8,14 but little is known about their actual use in clinical practice. An observational study designed to assess prior and concomitant use of psoriasis treatments in subjects receiving secukinumab (PROSPECT) found that at week 16 of treatment with secukinumab, 3.4% of patients were using concomitant therapies, with topical steroids being the most common.15 The results of our study conclude that more than 50% of patients continue to receive new prescriptions for topical steroids while receiving ongoing prescriptions for biologic medications. It is important to keep in mind that this analysis likely underestimates the percentage of patients who are actually using topical steroids, given that many patients may have remaining topical steroids from previously written prescriptions.
While these results provide novel insight in prescribing practices of biologic medications and concomitant therapies, there are important limitations that must be addressed. First of all, the information about prescriptions includes all prescriptions written and does not ensure that the medication was taken by patients. Additionally, information regarding the quantities of medication dispensed and refills authorized was not available, which may under estimate the duration of biologic therapy for some patients. While all medications analyzed are FDA approved for psoriasis, some medications have additional FDA-approved indications, and it is possible that drug utilization for non-psoriasis indications is different than for psoriasis and may be affecting the results. Finally, previous studies looking at drug survival have found lower rates of drug survival in patients utilizing second and third line biologic therapies. It is possible that reported time between first and last prescription may be longer if only true incident prescriptions were analyzed.
In conclusion, this analysis of EHR prescriptions in the United States found the median time between first and last prescriptions was between 3.3 and 7.0 months, and up to 50% of patients that receive a prescription for a biologic medication did not receive a second prescription for the medication. Additionally, use of concomitant topical steroids and methotrexate was common in patients receiving prescriptions for biologic therapies. By including all prescriptions written, this analysis provides novel insight in prescribing patterns for patients with psoriasis in the United States. The landscape of biologics medications to treat psoriasis is changing rapidly and it is important to understand shifts in prescribing practices as drug therapy continues to evolve.
Additionally, we also found a high percentage of concurrent methotrexate and topical steroid use in patients receiving prescriptions or biologic therapies, and use continued to be high, even after excluding the first 3 months after initiation of a biologic, suggesting ongoing use. Concomitant oral therapy use is consistent with what has been previously reported in the literature. Data from PSONET, a prospective network of psoriasis registries from Europe, found that 9.9% of biologic treatment cycles involved combination with a systemic therapy.11 Of these treatment cycles with combination therapy, 72.9% involved methotrexate, 25.3% involved UVB phototherapy, acitretin or cyclosporine and 1.8% involved PUVA, fumaric acids or a second biologic.11 HMO data from Israel showed that 7.1% of patients on adalimumab, 16.2% of patients on etanercept, 19.7% of patients on infliximab and 8% of patients on ustekinumab were taking methotrexate concomitantly, and 2.7% of patients on adalimumab, 2.2 % on etanercept, and 5.8% on ustekinumab were taking concomitant acitretin.12 Less than 1% of patients in each biologic group were taking cyclosporine, which is similar to what is reported in this study.
Previous research has suggested a benefit from the co-administration of methotrexate with biologics. Treatment guidelines from the medical board of the National Psoriasis Foundation report that combination treatment with etanercept and methotrexate or infliximab and methotrexate is more effective than monotherapy with either TNF inhibitor or methotrexate alone.13 Additionally, in drug survival analyses, methotrexate has been associated with in increased risk of drug survival.3,12 There are many reasons why a provider may prescribe concomitant methotrexate including loss of efficacy of the primary therapy, prevention of anti-drug antibodies and to enhance treatment effect in patients with psoriatic arthritis. With the advent of new, more efficacious biologic medications for psoriasis, continued research is necessary to understand the risk and benefits of concurrent methotrexate with newer drugs.
Guidelines also recommend that topical therapies are used as adjunctive therapy for patients with extensive psoriasis undergoing systemic therapy with phototherapy or biologics,8,14 but little is known about their actual use in clinical practice. An observational study designed to assess prior and concomitant use of psoriasis treatments in subjects receiving secukinumab (PROSPECT) found that at week 16 of treatment with secukinumab, 3.4% of patients were using concomitant therapies, with topical steroids being the most common.15 The results of our study conclude that more than 50% of patients continue to receive new prescriptions for topical steroids while receiving ongoing prescriptions for biologic medications. It is important to keep in mind that this analysis likely underestimates the percentage of patients who are actually using topical steroids, given that many patients may have remaining topical steroids from previously written prescriptions.
While these results provide novel insight in prescribing practices of biologic medications and concomitant therapies, there are important limitations that must be addressed. First of all, the information about prescriptions includes all prescriptions written and does not ensure that the medication was taken by patients. Additionally, information regarding the quantities of medication dispensed and refills authorized was not available, which may under estimate the duration of biologic therapy for some patients. While all medications analyzed are FDA approved for psoriasis, some medications have additional FDA-approved indications, and it is possible that drug utilization for non-psoriasis indications is different than for psoriasis and may be affecting the results. Finally, previous studies looking at drug survival have found lower rates of drug survival in patients utilizing second and third line biologic therapies. It is possible that reported time between first and last prescription may be longer if only true incident prescriptions were analyzed.
In conclusion, this analysis of EHR prescriptions in the United States found the median time between first and last prescriptions was between 3.3 and 7.0 months, and up to 50% of patients that receive a prescription for a biologic medication did not receive a second prescription for the medication. Additionally, use of concomitant topical steroids and methotrexate was common in patients receiving prescriptions for biologic therapies. By including all prescriptions written, this analysis provides novel insight in prescribing patterns for patients with psoriasis in the United States. The landscape of biologics medications to treat psoriasis is changing rapidly and it is important to understand shifts in prescribing practices as drug therapy continues to evolve.
DISCLOSURES
Megan Noe is supported by a K23-AR073932 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Daniel Shin and Jalpa Doshi have nothing to disclose. David Margolis receives research funding as the principle investigator via the Trustees of the University of Pennsylvania (R01-AR060962, R01- AR070873, and R01-DK116199) and from the NIH and Valeant Pharmaceuticals (PEER study) and Sunovion Pharmaceuticals. None of this funding was used for this study. He has consulting activities primarily as a member of data monitoring boards or scientific advisory boards with Leo, Johnson and Johnson,
