Alexandra B. Kimball, MD

Psoriasis (Pso) is a chronic immune-mediated systemic disorder with skin manifestations. Excessive skin cell production within the epidermis, in addition to the presence of dermal inflammation and dilated capillaries, can lead to signs and symptoms that include dry and cracked skin, red patches, skin itching, burning, and general skin soreness.

 Pso is the most common immune-mediated disease in the United States, with approximately 7.5 million Americans affected.

Treatment goals in Pso management are to reduce signs and symptoms and to alleviate patients’ discomfort and distress.

 Pharmacotherapy options for Pso are typically grouped into topical therapies, phototherapy, and systemic therapies including both systemic nonbiologic therapies (NBTs) and biologic therapies.

 Topical therapies are generally used as a first-line treatment for mild to moderate Pso cases, and aim to slow down excessive skin cell proliferation as well as to reduce the inflammation associated with Pso.

Phototherapy is generally prescribed in patients with Pso who are unresponsive to topical agents or have a large area of disease involvement, and is often used in combination with a systemic NBT to slow the rapid production of new skin cells and to reduce the discomfort caused by Pso manifestations.

Systemic NBTs are typically recommended as a second-line therapy in moderate to severe Pso cases that do not adequately respond to topical therapies or phototherapy.

 The most commonly used nonsteroidal systemic NBTs include methotrexate (MTX), acitretin, and cyclosporine. Biologic agents are recommended for patients with moderate to severe Pso who are candidates for systemic therapy or phototherapy but whose symptoms have not been adequately controlled using the aforementioned treatments.

Recently published studies on treatment patterns of Pso patients have investigated either treatment patterns in patients with a wide range of immune-mediated diseases, or in Pso patients initiated on specific biologics.

 However, despite the availability of treatment guidelines and clinical soriasis (Pso) is a chronic immune-mediated systemic disorder with skin manifestations. Excessive skin cell production within the epidermis, in addition to the presence of dermal inflammation and dilated capillaries, can lead to signs and symptoms that include dry and cracked skin, red patches, skin itching, burning, and general skin soreness.

This retrospective study used data from the US-based Truven Health Analytics MarketScan Research Databases for 2005 to 2009. These databases include approximately 25 million individuals, annually covered by 130 health plans and self-insured employers. The records contain information on patient eligibility, claims for inpatient and outpatient medical services, and pharmacy claims. Data are de-identified and comply with the patient confidentiality requirements of the Health Insurance Portability and Accountability Act.

Patients were included in the study if they had at least 2 independent diagnoses of Pso (

International Classification of Diseases, Ninth Revision, Clinical Modification 

code: 696.1x) over the entire observation period covered in the database, and if they initiated an oral NBT (including MTX, cyclosporine, or acitretin), phototherapy (PUVA or PUVB), or a biologic agent (including etanercept, infliximab, alefacept, efalizumab, ustekinumab, or adalimumab). For each sample (including oral NBT users, biologic users, and phototherapy users), the first prescribed medication and the first fill date were defined as the index treatment and the index date, respectively. All patients were aged at least 18 years as of the index date, were continuously enrolled in a health insurance plan that was linked to the database for at least 6 months before and at least 12 months after the index date, and had a Pso diagnosis as the latest immune-mediated disease prior to the index date. For the analysis of patients initiated on an oral NBT or phototherapy, patients were required not to have used any biologics, systemic NBTs, or phototherapy prescribed for their Pso or psoriatic arthritis before the initiation date of the oral NBT or phototherapy. Patients initiated on a combination of oral NBTs at the index date were excluded; however, those who were initiated on a combination of an oral NBT and phototherapy were included. Among patients initiated on an oral NBT, a subgroup of patients initiated on an oral MTX was also analyzed. Patients initiated on a biologic agent may have used a systemic NBT or phototherapy before the initiation of the biologic.

The study period was defined as the 12-month period following the index date, and the baseline period was defined as the 6-month period before the index date. Patients initiated on an oral NBT, phototherapy, or a biologic were analyzed separately. The 3 samples were not mutually exclusive; for example, a patient initiated on an oral NBT, who then switched to a biologic, could be included in both the oral NBT and biologic samples if the 2 index dates met all the selection criteria. No comparisons were conducted between the 3 samples.

Therapy change was defined as the discontinuation of the index treatment, a switch from the index treatment, or a therapy add-on. Patients were allowed to have more than 1 therapy change over the study period.

Treatment discontinuation was defined as a treatment interruption of at least 60 consecutive days for the index treatment (ie, a gap of at least 60 days between the end of 1 prescription and the start of the next prescription for the index treatment, or between the last prescription and the end of the study period). The discontinuation date was defined as the last day of the supply of the index treatment before the treatment gap. For patients initiated on phototherapy, treatment discontinuation was not analyzed, since discontinuation of phototherapy may have been due to completion of a defined phototherapy course. However, for patients initiated on phototherapy in combination with another oral NBT, discontinuation of the oral NBT was analyzed as part of the oral NBT and phototherapy patient group. Treatment discontinuation was captured from the index date up to the end of the 12-month study period.

Treatment switch was defined as the initiation of a treatment other than the index treatment within 60 days of the discontinuation of the index treatment, or within 60 days of the last phototherapy (as discontinuation was not analyzed for phototherapy). For patients initiated on an oral NBT, another systemic NBT that was not initiated on the index date (including MTX, acitretin, cyclosporine, sulfasalazine, leflunomide, azathioprine, mycophenolate, and anti-neoplastic agents), phototherapy, or a biologic were considered to be treatments the patient could potentially switch to. Patients initiated on phototherapy could switch to a systemic NBT or a biologic; those initiated on a biologic could switch to a systemic NBT, another biologic, or phototherapy. Additionally, as patients initiated on a biologic could have used a systemic NBT or phototherapy prior to the index date, the treatment being switched to could not have been taken during the 60-day period prior to the switch date. Treatment switches were captured from the index date up to 60 days after the discontinuation of the index treatment, or up to the end of the study period, whichever occurred first. All treatments initiated within the 60 days following treatment discontinuation were reported as a switch.

Therapy add-on was defined as the use of another systemic therapy or phototherapy for at least 28 consecutive days before the discontinuation of the index treatment. For patients initiated on an oral NBT, another systemic NBT that was not initiated on the index date, phototherapy, or a biologic were all considered potential add-on treatments. Patients initiated on phototherapy could have a therapy add-on with a systemic NBT or biologic; those initiated on a biologic could have a therapy add-on with a systemic NBT or phototherapy. As patients initiated on a biologic may have used a systemic NBT or phototherapy prior to the index date, the systemic NBT/phototherapy being added on could not have started during the 60-day period prior to the date of the therapy add-on. Therapy add-ons were captured over the period spanning from the index date up to the discontinuation of the index treatment, or until the end of the study period, whichever occurred first.

For patients initiated on an oral NBT or phototherapy, the 15 most frequent treatment sequences (up to the fourth treatment change) observed over the 12-month study period were reported. Treatment sequences were reported using 2 approaches: the first approach presents treatment sequences including treatment interruptions as part of the sequence—defined as an interruption of any systemic treatments for at least 60 days. The second approach presents treatment sequences without reporting treatment interruption as part of the sequences.

Patients and treatment characteristics during the baseline period. 

Descriptive information on patient and treatment characteristics during the baseline period or at the index date was reported separately for the 3 samples, as well as for the subgroup of patients initiated on MTX. 

shows patient baseline characteristics, which include age and gender, treatments taken at the index date (other than biologics), and, for patients initiated on a biologic, systemic NBT and phototherapy use prior to the index date. Reported characteristics also included the latest specialist encounter during the 30 days prior to the index date (including the index date), documented physical and mental comorbidities during the baseline period (only those with a prevalence of at least 5% are reported), and information from the Deyo-adapted Charlson Comorbidity Index.

All therapy changes of index treatment were reported separately for patients initiated on an oral NBT, on phototherapy, and on a biologic, as well as for the subgroup of patients initiated on MTX. The proportion of patients with at least 1 therapy change over the 12-month study period was reported. In addition, among patients with at least 1 therapy change during the study period, the proportions of patients who discontinued the index treatment, switched, or had a therapy add-on were reported. Among patients who switched or had a therapy add-on, the proportion that switched to or had a therapy add-on with a systemic NBT, phototherapy, or a biologic were reported. Additionally, among patients initiated on phototherapy, the proportion of patients who later used a systemic NBT or a biologic following an interruption of at least 60 consecutive days during the study period were reported. The median time to the observed therapy change was also reported. Median time to therapy change was calculated among patients who incurred the studied therapy change as the number of days between the index date and the date of the studied therapy change.

Overall, 4099 patients met the sample selection criteria and initiated an oral NBT on the index date, with the majority being initiated on MTX (

). Additionally, 79% of patients initiated on an oral NBT and 75% of patients initiated on MTX had at least 1 therapy change during the study period (

). The median time to the first therapy change was 77 days for patients initiated on an oral NBT, and 84 days for patients in the MTX subgroup. Among oral NBT patients who had at least 1 therapy change over the study period, 95% discontinued, 25% switched, and 10% had a therapy add-on (Figure 2). Although 95% of patients who had at least 1 therapy change also discontinued the index treatment during the 12-month study period, a significant portion of patients did not permanently discontinue all systemic Pso therapy; after discontinuation, 49% of patients resumed treatment with a biologic, a systemic NBT, or phototherapy at some point before the end of the study period (results not reported). Among patients who switched, the majority of patients switched to a biologic (69%), and among patients who had a therapy add-on, the majority of patients added a biologic (63%).

Among patients in the MTX subgroup who had at least 1 therapy change over the study period, 94% discontinued,

25% switched, and 11% had a therapy add-on. Similarly, though 94% of patients who had at least 1 therapy change discontinued the index treatment during the 12-month study period, the majority of patients did not permanently discontinue all systemic Pso therapy: 51% of patients resumed treatment with a biologic, a systemic NBT, or phototherapy at some point before the end of the study period (results not reported). Among patients in the MTX subgroup who switched, the majority of patients switched to a biologic (74%), and among patients in the MTX subgroup who had a therapy add-on, the majority of patients added a biologic (78%).

For patients initiated on an oral NBT who incurred at least 1 therapy change, the most frequent treatment sequences observed involved the use of a biologic as the next therapy following the index NBT initiation, either as a direct switch, a therapy add-on, or following the index NBT interruption (

Overall, 4391 patients initiated phototherapy on the index date (Figure 1). Among these patients, 15% had at least 1 therapy change during the 12-month study period (Figure 2). The median time to the first therapy change was 102 days. Among patients with at least 1 therapy change, 70% switched and 34% had a therapy add-on (Figure 2). Among phototherapy users who had an interruption of at least 60 consecutive days, 4% later used a biologic during the study period, and 3% later used a systemic NBT. Among patients who switched, 58% initiated a systemic NBT and 53% initiated a biologic. Among patients who had a therapy add-on, the majority of patients added a systemic NBT (69%). For patients who incurred at least 1 therapy change, the most frequent treatment sequences involved the use of a biologic therapy as the next therapy, either as a direct switch, a therapy add-on, or following the interruption of phototherapy (Table 2).

Overall, 6702 patients initiated a biologic therapy at the index date (Figure 1). Among these patients, 59% had at least 1 therapy change during the 12-month study period (Figure 2). The median time to the first therapy change was 113 days. Among patients who had at least 1 therapy change, 95% of patients discontinued treatment, 17% of patients switched, and 8% had a therapy add-on. Although 95% of patients who had at least 1 therapy change discontinued the index biologic treatment during the 12-month study period, most patients did not permanently discontinue all systemic Pso therapy: 63% of patients who discontinued resumed treatment with a biologic (43%), a systemic NBT (18%), or phototherapy (2%) at some point before the end of the study period (results not reported). Among patients who switched therapies, the majority of patients switched to another biologic agent (95%), and among patients who had a therapy add-on, the majority of patients added on with a systemic NBT (88%) (Figure 2).

The results of this study show that the majority of patients with Pso who were initiated on an oral NBT or a biologic did not remain on their index treatment for a long period of time. Among oral NBT patients who switched or had an add-on, most patients switched to or added a biologic, and among biologic patients who switched, the majority did so to another biologic. For patients initiated on phototherapy, most patients did not have a therapy change over the 12-month study period. In addition, results showed that among phototherapy users who had a therapy add-on or a switch, most patients had a therapy add-on with a systemic NBT and more than half of the patients switched to a biologic treatment.

Although reasons for the observed treatment changes were not available in the database, other studies have confirmed that despite the substantially broadened armentarium for the treatment of moderate to severe Pso, many patients remain dissatisfied with treatment or may not have access to adequate treatment due to insurance coverage restrictions.

 Reasons given by this group of dissatisfied patients primarily include adverse effects and a lack of effectiveness.

The low therapy change rate among phototherapy patients is partially explained by the fact that treatment discontinuation could not be easily analyzed for the phototherapy sample since discontinuation might be due to the completion of a phototherapy cycle. Additionally, the low rate could be explained by the high efficacy of this treatment in patients with moderate to severe disease. One study that tested directly for the efficacy of narrowband ultraviolet B phototherapy showed that it can vastly improve patient signs and symptoms and is effective in the majority of Pso cases.

 Another potential reason is the severity level of patients receiving phototherapy rather than systemic NBTs or biologics; however, there was no information available in the database about Pso severity. Among patients who had a treatment switch or therapy add-on, however, these therapy changes could potentially be explained by some of the unfavorable characteristics of phototherapy, which include the need to go to a physician’s office several times each week to receive assessment or therapy. Even in cases where phototherapy lamps are used at home, patients must make frequent visits to their physician’s office so that their progress can be monitored. Disadvantages of phototherapy also include an increased risk of skin cancer (mainly with PUVA); potential side effects including nausea, itching, and skin redness; and the high co-pays often associated with physician visits, which can create a financial burden for many patients.

In addition to the aforementioned potential causes of treatment changes, most healthcare insurance plans require patients to first use at least 1, and usually 2, systemic NBTs or phototherapies prior to granting insurance authorization for a biologic. This may also be a factor contributing to the high rates of therapy switch to or add-on of a biologic among patients initiated on an oral NBT or phototherapy. The high rate of switch from oral NBTs suggests that there may be a delay for adequate treatment for a substantial number of patients.

Two recently published studies on the use of biologics included a retrospective approach in the analysis of US-based research database records. The first study estimated discontinuation rates—defined as a 45-day treatment gap&mdash;in biologic-naïve patients who were diagnosed with either Pso, psoriatic arthritis, rheumatoid arthritis, or ankylosing spondylitis. This study found that over the 12-month study period, between 54% to 58% of patients discontinued therapy, depending on the biologic initiated.

 The second study estimated discontinuation rates in biologic-naïve Pso patients initiated on etanercept or adalimumab. This study found discontinuation rates similar to those in our study, with approximately 58% of patients discontinuing their index biologic—defined as a gap of at least 60 consecutive days of the index drug&mdash;over the 12-month study period.

Our study was subject to the common limitations of retrospective, observational studies that are based on healthcare claims data. First, the severity of Pso varies among individuals and the number of prior treatments used may affect a patient’s treatment profile. However, claims databases only record diagnostic and procedural codes, and do not indicate disease severity. Second, claims databases do not provide any information regarding the underlying reasons for therapy changes. Third, this study was restricted to the 12-month period following the initiation of an oral NBT. Further analyses are warranted to observe treatment patterns over a longer period of time. In addition, the study period was limited to the years 2005-2009, and patterns of biologic use may have changed in more recent years. In particular, ustekinumab was not approved by the FDA for treatment of Pso until September 2009. Since for the majority of the study period, ustekinumab had not yet been approved for the treatment of Pso, biologic treatment patterns would likely be different from those observed from a same analysis performed on more recent data. In addition, it is possible that the specialty of the treating/prescribing physician (eg, dermatologist vs general practitioner) impacts treatment patterns. Further studies would be warranted to assess the impact of treating/prescribing physician specialties on treatment patterns observed among Pso patients. Finally, patients with a diagnosis for psoriatic arthritis were not excluded from the study to select a sample of patients that are representative of a general Pso population requiring systemic therapies, where psoriatic arthritis is highly prevalent. However, in the absence of a diagnosis associated with prescription claims, we could not confirm that treatments were prescribed for dermatological symptoms rather than for psoriatic arthritis in patients with both conditions.

The results of this study showed that Pso patients initiated on an oral NBT or a biologic did not remain on the index treatment for a long period of time. Most patients experienced at least 1 therapy change, with the first change generally occurring within 4 months of initiation of treatment. Among the patients initiated on an oral NBT who had a therapy add-on or a treatment switch, the majority had a therapy add-on with a biologic or switch to a biologic treatment. Among the patients initiated on a biologic who switched from the index treatment, the majority switched to another biologic treatment. Although most phototherapy users did not have a therapy change over the study period, most patients with at least 1 therapy change had a therapy add-on with a systemic NBT and more than half of the patients switched to a biologic treatment. These results suggest that Pso remains a challenging disease to treat and currently requires a broad range of therapeutic options. A better understanding of the factors related to early therapy changes in Pso patients is needed.

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