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Sequential use of biologics

Sequential use of biologics

This chapter provides an overview of the pharmacological rationale and clinical evidence for sequential use of biologic therapies, and discusses how clinical evidence can guide their use

Phyllis I Spuls MD PhD Department of Dermatology, Academic Medical Centre, Amsterdam, The Netherlands

Circumstances under which a patient will initiate with a biologic differ from country to country and probably within countries. There is a variation in treatment strategies and variation in treatment availability. Direct medical costs for biologics are extremely high and therefore strict reimbursement criteria dictate when biologics are indicated. Biologics will often be initiated when patients have insufficient response to, contraindications or intolerance for topical, photo(chemo) – and conventional systemic therapies. Patient preferences may also play a role. More comparative data of efficacy, effectiveness (data from clinical practice and of subgroups of patients, for example, the elderly, patients with specific comorbidities), safety and efficiency of all treatment modalities should become available and implemented in clinical practice. Many factors play a role when choosing a biologic as preferable treatment for chronic plaque-type psoriasis. Among these factors are the presence of psoriatic arthritis (PsA) and/or nail psoriasis, the efficacy, effectiveness, onset of action and safety of treatments, the age of the patient, the wish to conceive, comorbidities, perhaps costs and, last but not least, patient preferences. Some guidelines do discuss biologic strategies.1–3

How to choose 28 Primary selection is dependent on whether

the patient also suffers from PsA and/or nail psoriasis concurrently with plaque-type psoriasis.

The tumour necrosis factor a (TNFa) inhibitors (anti-TNFs) adalimumab, etanercept and infliximab and recently the interleukin (IL)-12/23 inhibitor ustekinumab are registered for chronic plaque-type psoriasis and PsA. In patients with combined chronic plaque-type psoriasis and PsA, a multidisciplinary approach with dermatologists and rheumatologists is important. There is no definite consensus for a treatment algorithm with anti-TNFs and IL-12/23 inhibitors due to the fact that there are no strategic trials performed in PsA. The recommendations in the EULAR treatment guideline4

are based on combining evidence

and expert opinion, though it should be noted that ustekinumab was not yet indicated in PsA at the time of publication. For active PsA, it is recommended to treat with non-steroidal anti-inflammatory drugs ± local glucocorticoid injections in the first three to six months. In case of lack of efficacy and/or toxicity or adverse prognostic factors (for example ≥ 5 active joints), methotrexate therapy as disease-modifying anti-rheumatic drugs (DMARDs) is advised. In the next phase, treatment with an anti-TNF or IL-12/23 inhibitor ± DMARD is advised for patients with adverse prognostic factors. Anti-TNFs have proven to be effective in PsA, with no evident differences between the anti-TNFs regarding efficacy. In case of skin involvement, adalimumab and infliximab will be preferred above etanercept.5

Nail psoriasis

Nail psoriasis has been shown to have a huge impact on the quality of life of patients.

Severely affected nails may play a role in selecting a biologic. Most evidence for efficacy is available for infliximab.6 Ustekinumab may also improve nail psoriasis but more evidence is needed.7


evidence for etanercept versus infliximab will become available soon.8 For adult chronic plaque-type

psoriasis without PsA or nail involvement, the efficacy, effectiveness, short- and long-term safety and the severity and reversibility of adverse events, the mode of administration and cost play a role in choosing a biologic. Adalimumab, etanercept and infliximab as well as ustekinumab have been proven (high level of evidence) effective for chronic plaque-type psoriasis. Indirect and direct comparisons (short-term studies) show that the efficacy of adalimumab, infliximab and ustekinumab are better than etanercept. Patients and physicians must realise that clinical practice data (effectiveness) sometimes show different and less favourable effects than data from clinical trials (efficacy).9

Newer drugs with less long-term data need to instil confidence before they can be selected. The NICE guideline10,11

advises the

use of ustekinumab after failure of the anti-TNFs. However, ustekinumab is gaining more reliability, now that five-year data are available.12 Moreover, the onset of action of biologics might also play a role in choosing a biologic agent. Nast et al have summarised the evidence concerning time to onset of action (TOA). TOA is defined as the weighted mean time until 25% of the patients achieve a psoriasis area and severity index (PASI) 75 response. Limited assessment is possible

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