**3.2 Prior systemic treatment**

Prior treatments received for psoriasis are stereotypical: before authorizing biological therapy, Belgian regulations require patients to have tried three therapeutic channels: PUVA therapy, cyclosporine, and methotrexate. It is noted that this refers to PUVA therapy proper, and not just UVB treatment. For cyclosporine, a 'minimum of 2 months of therapy' is stipulated, 'at a minimum of 2.5 mg/kg.day'. For methotrexate, a minimum of 3 months is required, at 15 mg minimum per week. Infringements to either requirement can be made only in the case of documented intolerance or absolute contra-indication.

Among the 46 patients, one was Argentinian and had been able to begin biological therapy in his country without going through the three prior steps; the Belgian authorities therefore authorized him to take infliximab immediately. Another patient had mild renal insufficiency and unstable blood pressure despite the treatment, which was deemed sufficient to certify contra-indication to cyclosporine. The remaining 44 patients all received the three standard treatments, in some cases also UVB, acitretin, or spa treatments. None received fumaric acid (not used in Belgium). Reasons for discontinuing prior treatments included the absence of sufficient clinical results, or an intolerance to the treatment, as well as the prevention of side affects after reaching an excessive cumulative dose. Note: one of the patients had renal insufficiency induced by prolonged cyclosporine therapy.

#### **3.3 Choice of biological therapy**

No regulations lay down the use of a specific first-line biological therapy. It would no doubt be logical to begin with a TNF inhibitor, before considering an anti-interleukin, such as ustekinumab, however no objective data exists to support this affirmation. This rationale lies merely in a lack of experience and appraisal with ustekinumab, as opposed to the years of experience with TNF inhibitors, infliximab in particular. There is no way to choose one product over another among TNF inhibitors. Suggestions to begin with etanercept are based on certain data emerging from records, but these are not sufficiently back-up. In the end, the choice of first-line biological therapy currently depends on the habits of the prescriber and discussions with the patient.

In our case series, 15 patients have received infliximab as first-line treatment. The choice was laid out by presenting the patient with the different options, along with their known

Infliximab Therapy for Plaque Psoriasis: The UCL Experience 277

When we compared the response to infliximab in biotherapy naive and non-naive patients, we found no significant difference, contrary to our expectations. The two groups have the same numbers of complete responses and there is no difference in the subsequent relapse rate.

The average duration of treatment (stopped on the day of database analysis) is 604 days, with extremes of 14 and 1666 days. This duration is long enough to draw conclusions, at least partial ones. The 14-day duration corresponds to a treatment stopped due to side effects.

Clinical response is often excellent. Primary response must be distinguished from more long-term response. Primary response is immediate efficacy, generally deemed at 10 weeks for infliximab. The more long-term response is the persistence of efficacy, without relapse; there is no defined timeframe for measuring this. We will therefore talk about a 1-year or 2 year response, etc. For this study, we analyzed the long-term response according to the clinical practice at the time of file analysis, so 1 to 4 years after the beginning of treatment.

A review of the literature indicates excellent clinical response rates to infliximab after 10 weeks: around 80% at PASI 75 (Chaudhari et al., 2001). In other words: four patients out of five achieve a three-quarter response at minimum (reduce their initial PASI by 75% minimum). In our series, this was true for 31 out of 41 assessable patients, so 76%. 19 patients (46%) had a complete response (total clearance of lesions) (table 1). 6 patients achieved a PASI reduction of between 90 and 99%. 6 others reduced their PASI by a

**3.4 Duration of treatment** 

**3.5 Efficacy of infliximab** 

Fig. 2. W0, baseline

advantages and disadvantages. Many patients appreciate the simplicity of infliximab's dosage schedule: half a day in hospital every eight weeks seems much easier than more regular injections at home. Patients often say: "at least, with the drip, I can forget about psoriasis and its treatment completely for two whole months". Patients do not have to go to the pharmacy on a regular basis, keep boxes in the family refrigerator, or have a nurse repeatedly visit their house (figure 1).

Fig. 1. Infusion in specialized unit

On the other hand, some patients fear the hospital environment and prefer treatments they can manage independently. This explains the figure of 31 patients who began infliximab as second- or third-line treatment. Of these patients, the majority had begun with etanercept, with a clinical response deemed insufficient. Some had begun with adalimumab, with a subsequent secondary clinical relapse. Some patients used these two products before beginning infliximab. One patient had received ustekinumab, with a good clinical result, but the development of a paradoxical eczematous reaction.

When we compared the response to infliximab in biotherapy naive and non-naive patients, we found no significant difference, contrary to our expectations. The two groups have the same numbers of complete responses and there is no difference in the subsequent relapse rate.
