Alternative dosing schedules for ustekinumab therapy

Non-standard treatment regimens are increasingly being used when prescribing biologic agents. Several studies examine this scenario for adalimumab, etanercept and infliximab (1). The beneficial effect of ustekinumab has been shown at the recommended initial dose of 45 mg or 90 mg subcutaneously (weight adjusted for patients less than or greater than 100 kg respectively), followed by a week four dose and 12 weekly dosing thereafter (2). More frequent dosing schedules are currently unlicensed.

We aimed to assess our patients on ustekinumab to determine how many patients were on increased dosing schedule and if there was a subsequent improved response. This was a retrospective multicentre study of patients treated with ustekinumab treatment (n = 51) from 2009 to 2013 with follow-up to February 2014 at the South Infirmary Victoria University and Waterford Regional Hopsitals. Prior to commencing treatment, all patients had undergone pretreatment investigations as recommended by the British Association of Dermatologists’ guidelines (3).

Of the total cohort, all but three had a diagnosis of psoriasis, one each had eczema, hidradenitis suppurativa and pityriasis rubra pilaris. All patients had prior treatment with either an alternative systemic immunosuppressants or biologics and were unresponsive. Of the total cohort: 12 patients (24%), 11 of whom had psoriasis and 1 with a diagnosis of eczema, were receiving increased dosing schedules due to partial response or flare. A further one patient weighing <100 kg was receiving 90 kg 12 weekly. Baseline characteristics are shown in Table 1. Further details of dose escalation are shown in Table 2. All but patient was either clear or exhibited an improved response on increased dosing schedule or dose as assessed by physicians clinical assessment. Blood test monitoring did not reveal any abnormalities. No patients developed infectious side effects. No other side effects occurred.

Table 1. Characteristics of patients receiving dose escalation.

Dose escalation	n
Sex
Male	10
Female	3
Diagnosis
Psoriasis	12
Eczema	1
Why dose increased
Partial response	5
Flare	8
Ustekinumab first line biologic	5
Age dose escalated (yrs) (mean)	41
Age dose escalated (mths) (median)	14

Table 2. Dosing regimens.

Dose intervals	n
90 mg 10 weekly intervals	5
90 mg 9 weekly intervals	1
90 mg 8 weekly intervals	1
45 mg 10 weekly intervals	4
45 mg 8 weekly intervals	1
90 mg 12 weekly intervals
Weight < 100 kg	1

In the Phoenix 1 and 2 trials dose adjustment was allowed for partial responders (2,4). In both of these phase III studies, dosage was randomly assigned and not weight adjusted. In Phoenix 1, partial responders showed improved PASI 75 response rates when the dose was increased to 8 weekly (2). In Phoenix 2, there was no improvement in patients receiving 45 mg 8 weekly as compared with those receiving 12 weekly dosing (4).

We describe 13 patients receiving increased dosing of ustekinumab. Twelve of the 13 remain well-controlled on these regimens. Dose escalation for ustekinumab was efficacious and well-tolerated in patients with psoriasis who fail to achieve response on the licensed dosing schedule. We suggest that the optimal dosing schedule may differ between patients. Further studies are warranted to assess the potential benefit of dose escalation of ustekinamab in this setting.

Declaration of interest

No funding was received for this work. None of the authors have any conflicts of interest to disclose.