**4.2 Adverse events**

Few adverse events were observed, but these were occasionally severe.

One death by suicide, of a 30 year old man. The patient had been depressed for a long time, with a first suicide attempt long before the infliximab treatment. The psychological followup was good, but the patient was unable to cope with a failed love affair. The doctor considered this suicide as unrelated to the infliximab treatment. Similarly, a 67 year old patient reported an aggravated impotence problem since the first infliximab infusions. He decide to stop the treatment, which left the effect on erectile function unclear. He had reported the same problem during methotrexate treatment, with recovery after discontinuation. Urological examination results were normal.

Overall, we did not observe any significant infection. Specifically, we did not note any opportunistic infection or any tuberculosis. There were no severe infections to justify a deferral of the infliximab infusion, and anti-infective treatment did not need to be increased in any case.

One patient suspended their treatment during cardiac surgery on the mitral valve (condition pre-existing the infliximab treatment).

For six patients, the obligation to discontinue treatment was more acute (see table 3).

The two cases of induced lupus were severe and required hospitalization. Remission was slow. The first patient had already been treated with infliximab, with an excellent initial clinical response but a relapse after one year. The treatment was stopped for 9 months, but the administration of adalimumab was not conclusive, and the patient wished to try infliximab again. Ten days after the first re-introduced infusion, the patient experienced joint pain and swelling, with rapidly-progressive functional disability leading to an incapacity to move, and hospitalization. The second patient, on methotrexate from the start, developed signs of articular lupus from the 9th month of infliximab treatment, with seroconversion. After the 11-month infusion, the seizure was acute, incapacitating, requiring hospitalization and the use of corticosteroids, and then even thalidomide. It was possible to discontinue the latter after six months.

Infliximab Therapy for Plaque Psoriasis: The UCL Experience 283

For patients 5 and 6, the anaphylactic reactions were true. For the first patient, the shock arose on the 2nd infusion after treatment reintroduction. The patient had participated in the Centocor EXPRESS clinical trial (C0168T38) in 2003 and 2004. The treatment had been stopped for 2 years, with use of etanercept. The infliximab treatment could be restarted after the anaphylactic shock, with systematic preventive measures, progressively reduced, but without the possibility of complete cessation. Clinical efficacy was reduced: less complete response, and period of 8 weeks between two infusions became too long. This justified the discontinuation of infliximab 4½ years later. The reaction was less severe for the second patient. The treatment was also continued, with prevention, but a clinical relapse appeared, which became complete six months later (no improvement after infusion). This patient

10 patients experienced temporary interruptions to treatment. The reasons varied widely.

response. The doctor therefore suggested a treatment more in line with their lifestyle.

successfully and without adverse events, after recurrence of psoriasis.

unsettled, and he was no longer allowed to claim his treatment fees.

One patient had to go on a extended trip abroad.

One patient interrupted treatment for a clinical drug trial.

Two patients were not compliant: they forgot appointments on several occasions and canceled due to 'lack of time'. Several times, this led to delays of up to three months. This did not affect tolerance for either patient, but one of the two had an insufficient clinical

One patient personally chose to have a drug holiday; he was able to restart treatment

One patient (already mentioned above) had to interrupt infliximab for nearly six months

One patient interrupted treatment for several months, as his Social Security status was

Several patients who had received infliximab therapy for several years recently expressed interest in switching to a biological therapy administered subcutaneously, which they had heard about and considered easier to manage. However, the beginning of treatment is often difficult (partial recurrence following the discontinuation of infliximab), and efficacy of the new treatment is not always immediate. Three patients experienced the change badly and tolerated the beginning of the recurrence poorly. Despite medical explanations and the concern for avoiding drug 'shopping', they returned to their prior infliximab treatment. The reintroduction was accompanied by manifestations of hypersensitivity in

Infliximab treatment usually involves strong adherence by the patient. When efficacy is maintained in the long-term, the patient is especially grateful for this invariability. All patients consider not having to undergo treatment at home as being very positive. The

currently has a partial response to ustekinumab.

**4.3 Drug holidays** 

due to repeated heart surgery.

one case only.

**4.4 Adherence to treatment** 


Table 3. Observed adverse events

For patient 3 (see table), resistant to adalimumab from the start, adverse effects arose from the first infliximab infusion: chest pain with normal tracing on the ECG, unremarkable blood pressure and pulse. The second infusion had to be stopped (faintness) and resumed the following week, with premedication. On the following three days, the patient had to visit the emergency department for incapacitating inflammatory joint pain. The patient was off work for 24 hours. The clinical result was good (PASI reduced to 80%). The third infusion gave rise to the same joint pains, increased, diffused, with headaches. The treatment was discontinued and replaced with ustekinumab, with no tolerance problem.

Patient 4, who was resistant to etanercept, initially showed an excellent response to infliximab (98% PASI improvement). After around 10 months, the recurrence preceding each infusion came earlier and earlier. The treatment was discontinued after 17 months, after it had lost all effect and inflammatory, atypical joint pain had developed for several days and then weeks following the last two infusions, despite the use of methotrexate (begun very late).

For patients 5 and 6, the anaphylactic reactions were true. For the first patient, the shock arose on the 2nd infusion after treatment reintroduction. The patient had participated in the Centocor EXPRESS clinical trial (C0168T38) in 2003 and 2004. The treatment had been stopped for 2 years, with use of etanercept. The infliximab treatment could be restarted after the anaphylactic shock, with systematic preventive measures, progressively reduced, but without the possibility of complete cessation. Clinical efficacy was reduced: less complete response, and period of 8 weeks between two infusions became too long. This justified the discontinuation of infliximab 4½ years later. The reaction was less severe for the second patient. The treatment was also continued, with prevention, but a clinical relapse appeared, which became complete six months later (no improvement after infusion). This patient currently has a partial response to ustekinumab.
