WHAT ARE BIOLOGICALS / BIOLOGICS ?Biologics are artificially produced proteins that have the same structure as proteins naturally occurring in our bodies. Most of the biologicals used as medicines are antibodies, directed against a naturally occurring protein. This is often a protein that plays a role in maintaining inflammation in the body. Because the artificially produced antibody binds to this protein, the inflammation is inhibited.
For example, the biological infliximab (brand names Remicade , Remsima , Inflectra ) is an artificially produced antibody that binds to the substance TNF-alpha found in the body . TNF-alpha is a protein that plays a role in various inflammatory processes in the body. Infliximab ( anti-TNF-alpha ) inhibits these inflammatory processes by binding to TNF-alpha.
TNF-alpha is produced in the body by cells that are part of our immune system. It is released where something is wrong, for example, a bacterial infection, inflammation, or damage. The release of TNF-alpha amplifies the inflammatory response: white blood cells (leukocytes) are attracted and activated, causing even more inflammation. This causes local redness, warmth, swelling, and pain.
This inflammatory response is a normal mechanism in the body, intended to eliminate bacteria, for example. But there are diseases in which the inflammatory response spirals out of control and causes damage to the surrounding tissues. This occurs, for example, in Crohn's disease (inflammation of the bowel), rheumatoid arthritis (inflammation of the joints), and psoriasis (inflammation of the skin). In all these conditions, inflammation can be inhibited with infliximab (anti-TNF-alpha).
Besides TNF inhibitors, there are also other biologics, with different targets, on the market, and new ones are introduced almost every year. The first biologic for psoriasis was Enbrel (etanercept) (a fusion protein of the TNF receptor and IgG1). Remicade (infliximab) and Humira (adalimumab) (both anti-TNF-alpha) followed. Since 2009, Stelara (ustekinumab) (anti-IL12, anti-IL23) has also been available, and since 2015, Cosentyx (secukinumab) (anti-IL-17A) and Otezla (apremilast) (not a biologic, but a phosphodiesterase E4 inhibitor, inhibits TNF-alpha, IL-23, IFN-alpha, and IFN-gamma). In 2016, Taltz (ixekizumab) (anti-IL-17A) was also approved for the Dutch market. In October 2017, Kyntheum (brodalimumab) was introduced.(anti-IL-17-RA) on the market, in 2018 Tremfya (guselkumab) (anti-IL23), in 2019 Ilumetri (tildrakizumab) (anti-IL23) and Skiryzi (risankizumab) (anti-IL23), and in 2021 Bimzelx (bimekizumab) (anti-IL-17-AF).WHICH BIOLOGICALS ARE THERE?There are currently (2025) 13 biologicals available in the Netherlands for psoriasis (Otezla is not a biological):
| Brand name |
substance name |
directed against |
administration |
how often |
| Enbrel |
etanercept |
TNF-alpha |
injection by patient himself |
twice a week |
| Humira |
adalimumab |
TNF-alpha |
injection by patient himself |
1 x every 2 weeks |
| Remicade |
infliximab |
TNF-alpha |
through an IV in a clinic |
1 x every 2 months |
| Cimzia |
certolizumab |
TNF-alpha |
injection by patient himself |
1 x every 2 weeks |
| Stelara |
ustekinumab |
IL-12 and IL-23 |
injection by patient himself |
1 x every 3 months |
| Cosentyx |
secukinumab |
IL-17A |
injection by patient himself |
1 x every 4 weeks |
| Taltz |
ixekizumab |
IL-17A |
injection by patient himself |
1 x every 4 weeks |
| Kyntheum |
brodalumab |
IL-17RA |
injection by patient himself |
1 x every 2 weeks |
| Tremfya |
guselkumab |
IL-23 |
injection by patient himself |
1 x every 8 weeks |
| Ilumetri |
tildrakizumab |
IL-23 |
injection by patient himself |
1 x every 12 weeks |
| Skiryzi |
risankizumab |
IL-23 |
injection by patient himself |
1 x every 12 weeks |
| Bimzelx |
bimekizumab |
IL17AF |
injection by patient himself |
1 x every 8 weeks |
| Otezla |
apremilast |
TNF-α, IL-23,
IFN-alpha, IFN-gamma |
tablets |
30 mg twice a day |
| Sotyktu |
deucravacitinib |
TYK2 |
tablets |
1 x daily 6 mg |
The way these biologics work is quite complex. But the essence is that they neutralize the effects of proteins that cause inflammation. The details are explained below.
Humira (adalimumab)
. Adalimumab is a man-made humanized monoclonal antibody that binds to TNF-alpha. This inhibits various inflammatory processes in the body, including psoriasis. Monoclonal means that all antibodies are of the same type, identical, and all target a single protein, in this case TNF-alpha. The English term is monoclonal antibody (mab), which is why all these drug names end with mab. Humanized means that the composition of the adalimumab protein is such that it is indistinguishable from proteins produced by the human body itself. Humira is available as syringes containing 40 mg of adalimumab. This must be administered by yourself every two weeks into your thigh. See the leaflet about Humira for more information .
Enbrel (etanercept)
Etanercept also binds to TNF-alpha and neutralizes its effects. Etanercept is not an antibody, but a receptor protein. That's why the drug's name ends with "cept." A receptor protein is normally attached to the outside of a cell that is part of the immune system. There is also a receptor that TNF-alpha fits perfectly into. Through this receptor, TNF-alpha can activate the inflammatory cells: as soon as TNF-alpha binds to the receptor for TNF-alpha on the cell surface, something happens in that cell and the cell becomes active. By now providing a large number of individual receptor proteins (etanercept) from the outside, the TNF-alpha molecules are captured. Enbrel is available in 25 or 50 mg syringes. Usually, the dose is started with a 50 mg injection twice a week. If this goes well, the dose can be reduced to 25 mg twice a week, or 50 mg once a week. See also the leaflet about Enbrel .
Remicade (infliximab)
Infliximab is also a synthetic monoclonal antibody that binds to TNF-alpha. This inhibits various inflammatory processes in the body, including psoriasis. The difference with adalimumab is that infliximab is not 100% humanized. The protein still contains some small fragments that do not completely match the human protein. This makes the risk of allergic reactions to infliximab slightly higher than with adalimumab. The other major difference is that adalimumab can be administered at home by injection, while infliximab requires an infusion, which requires a visit to a hospital or infusion clinic. The amount of infliximab needed is calculated based on your body weight. Most patients will need four ampoules of 100 mg. This total amount of 400 mg is then administered by infusion. Afterward, you will have to stay for another hour for a check-up. Two weeks later, you will receive another infusion. Four weeks later (week 6), you will receive the third dose. After that, it will be every two months. See the leaflet about infliximab for more information.
Stelara (ustekinumab)
Ustekinumab is also a human monoclonal antibody. It does not target TNF-alpha, but two other substances that play a role in the inflammatory process in psoriasis: interleukin 12 (IL-12) and interleukin 23 (IL-23). By inhibiting these two interleukins, psoriasis improves. Ustekinumab is administered by injection, and you can administer it yourself. The dose is 45 mg (1 injection with 0.5 ml ustekinumab). This should be repeated after four weeks. After that, it only needs to be repeated every three months. If you are overweight (over 100 kg), you should use double the dose (2 injections).
Stelara has been fully reimbursed since 2009 for patients with moderate to severe plaque psoriasis in whom PUVA therapy, methotrexate, and ciclosporin were ineffective or had to be discontinued due to side effects. See the Stelara brochure for more information.
Cosentyx (secukinumab)
Secukinumab inhibits interleukin 17A (IL-17A). Interleukin 17A is also a substance that plays a role in the inflammatory process in psoriasis. Anti-IL-17A inhibits inflammation and reduces psoriasis. Cosentyx (secukinumab) is started with a loading dose of 300 mg (2 injections of 150 mg) in weeks 0, 1, 2, and 3, followed by a 300 mg dose every 4 weeks.
Taltz (ixekizumab)
Ixekizumab inhibits interleukin 17A (IL-17A). Interleukin 17A is also a substance that plays a role in the inflammatory process in psoriasis. Anti-IL-17A inhibits inflammation and reduces psoriasis. Taltz (ixekizumab) is administered as a loading dose of 2 x 80 mg at week 0, 80 mg at weeks 2, 4, 6, 8, 10, and 12, and then 80 mg every 4 weeks.
Kyntheum (brodalumab)
Brodalumab is a man-made human monoclonal antibody that binds to the protein interleukin 17 RA (IL-17RA). This inhibits various signal proteins that play a role in the inflammatory process in psoriasis, such as IL-17A, IL-17F, IL-17A/F heterodimer, and IL-25. As a result, brodalumab inhibits the inflammation and clinical symptoms of psoriasis. Kyntheum (brodalimumab) is given in a loading dose of 210 mg (1 pre-filled syringe) at weeks 0, 1, and 2, and then every 2 weeks.
Bimzelx (bimekizumab)
Bimekizumab inhibits interleukin IL-17A, IL-17A/F, and IL-17F, substances (cytokines) that play a role in the inflammatory process in psoriasis. The usual dose is 320 mg every 8 weeks, after a loading schedule (320 mg (2 x 160 mg syringes or 1 x 320 mg syringe) in weeks 0, 4, 8, 12, and 16). Patients who weigh more than 120 kg and are not completely psoriasis-free after 16 weeks can receive a higher dose (every 4 weeks).
Tremfya (guselkumab)
Guselkumab is a human monoclonal antibody that targets interleukin 23 (IL-23). By inhibiting interleukin 23, it improves psoriasis. Guselkumab is administered as an injection, and you can administer it yourself. The dose is 100 mg (1 injection of 1 ml of guselkumab 100 mg/ml) in weeks 0 and 4, and then every 8 weeks.
Ilumetri (tildrakizumab)
Tilldrakizumab is a human monoclonal antibody directed against interleukin 23 (IL-23). By inhibiting interleukin 23, psoriasis improves. The dosage is 100 mg in weeks 0, 4, and then every 12 weeks.
Skiryzi (risankizumab)
risankizumab is a human monoclonal antibody directed against interleukin 23 (IL-23). By inhibiting interleukin 23, psoriasis improves. The dosage is 150 mg in weeks 0 and 4, then 150 mg once every 12 weeks.
Otezla (apremilast)
Apremilast is not a biologic, but a small molecule that inhibits a substance called phosphodiesterase E4. This indirectly inhibits the substances TNF-α, IL-23, IFN-alpha, and IFN-gamma. This reduces inflammation in psoriasis. Otezla (apremilast) is given as tablets. The dose is based on a build-up schedule: day 1: 10 mg, day 2: 20 mg (2 x 10 mg), day 3: 30 mg (10 mg + 20 mg), day 4: 40 mg (20 mg + 20 mg), day 5: 50 mg (20 mg + 30 mg), then 30 mg twice daily. A set of 10, 20, and 30 mg tablets is available for the build-up schedule.WHEN AM I ELIGIBLE FOR BIOLOGICALS?Biologics are very expensive, ranging from approximately €9,000 to €20,000 per year (see below). Therefore, certain conditions apply to their reimbursement. You are eligible for treatment with biologics if your psoriasis is severe and does not respond or responds insufficiently to standard treatments. Psoriasis is considered severe if it has reached a certain extent (covering a large part of the body) or if it has a significant negative impact on quality of life.
Whether you are eligible for treatment is not just about the money. Many psoriasis patients consider biologics to be miracle cures, but they do affect the immune system, lowering it and can also have side effects. Therefore, they are not prescribed lightly, but only if standard treatments are ineffective, insufficient, or have too many side effects. Common psoriasis treatments include hormone ointments and other ointments, light therapy with UVB or PUVA, as well as treatments with tablets such as MTX (methotrexate), Neoral (cyclosporine), Neotigason (acitretin), and fumarates. For more information about these medications, see the psoriasis brochure .
Common psoriasis medications such as MTX, Neoral, Neotigason, and fumarates can also have side effects, sometimes severe and a reason to stop taking them altogether. On the other hand, there are also patients who use methotrexate for years, for example, without experiencing any symptoms. There's nothing wrong with these medications; they haven't suddenly become "outdated" just because biologics are available. They've been in use for decades, and therefore a great deal is known about their effects and side effects, including the long-term effects after years of use. Much less is known about the long-term effects of biologics, which are newer.
That is why it is wise to try the usual remedies first, and only start using biologicals if they no longer work or are no longer possible (due to side effects).WHICH BIOLOGICAL DOES IT START WITH, AND WHAT DETERMINES THE ORDER?Biologics haven't been on the market for very long, and new ones are still being added. All biologics have been carefully tested for effectiveness and safety. However, to determine which works best and has the fewest side effects, comparative research between the different biologics is needed. This requires studying a large group of psoriasis patients, who are then given either one or the other. This type of research hasn't been widely conducted yet. Therefore, we must rely on the experience of doctors who are used to prescribing these medications frequently.
In most specialist centers, patients currently start with Humira (adalimumab) or Enbrel (etanercept). Because Humira only needs to be administered biweekly and Enbrel twice a week, Humira is usually chosen for its ease of use. If Humira isn't effective enough or if its effectiveness deteriorates, one of the other biologics is started. If Enbrel is effective, it can often be continued for years without any problems. If Enbrel doesn't work well (even at the high dose of 50 mg twice a week), Stelara could be tried next. Because Stelara is so easy to use (only one injection every three months), it's usually chosen after Humira and Enbrel. Remicade (infliximab) can only be administered intravenously in a clinic. For very severe psoriasis that needs to be controlled quickly, Remicade is sometimes a better first choice because this intravenous drug is more potent than both Humira and Enbrel. It's also possible that Enbrel and Humira don't work well, but Remicade does. Sometimes, biologics work well initially, but their effectiveness diminishes over time. In this case, antibodies may have formed against the biologic, which neutralize its effects. This can be measured in the blood. This is mainly seen with Remicade and to a lesser extent with Humira. There are indications that the formation of these antibodies can be prevented by combining Remicade and Humira with a low dose of methotrexate (7.5 mg per week). The newest drugs, Cosentyx (secukinumab), Otezla (apremilast), Taltz (ixekizumab), Kyntheum (brodalimumab), Tremfya (guselkumab), Ilumetri (tildrakizumab), Skiryzi (risankizumab), and Bimzelx (bimekizumab), are currently mainly administered if the others are ineffective. Over time, as more experience is gained, the order of administration may change. The order of administration of the expensive drugs may also depend on the purchasing policy and price agreements the hospital has made with the manufacturers.IS ANY SPECIAL RESEARCH NECESSARY?Before treatment, blood tests are often performed: a general blood test and tests for infections such as tuberculosis (TB) or hepatitis (liver inflammation). Before starting a TNF inhibitor (infliximab, adalimumab, etanercept), it must be confirmed that you do not have tuberculosis, as this can flare up when using TNF inhibitors. Therefore, people at risk of tuberculosis infection will have a lung x-ray and a Mantoux test performed in the arm. This is a skin prick that tests whether you have ever been exposed to the tuberculosis bacteria. The Mantoux test is read after 3 to 5 days; no lump should be visible at the injection site. If a lump does appear (positive Mantoux), you should see a pulmonologist to determine whether you have a history of tuberculosis. It's important for women to know if there's a possibility of pregnancy, so a pregnancy test is performed before starting treatment. There are no known harmful effects of biologics on the unborn fetus. The package insert usually states that they should not be used during pregnancy and breastfeeding, but several biologics are now known to be safe and can be continued during pregnancy. Discuss this with your prescribing physician.
Blood tests are also sometimes performed during treatment to monitor for side effects, such as liver dysfunction.ARE BIOLOGICALS SAFE?All biologics have been extensively tested for effectiveness and side effects before being allowed on the market. All the biologics mentioned are registered in the Netherlands for the indication moderate to severe plaque psoriasis. This means that the registration committee has assessed their effectiveness and safety and found them to be in order. This does not mean that side effects cannot occur. All medications can have side effects, even the simplest painkiller paracetamol. The benefits and risks must be weighed against each other. You should always carefully read the package insert so that you are aware of the possible side effects. If a side effect occurs, the biologic may have to be stopped. You can then still try one of the other biologics.WHAT ABOUT THE FLU? DO I NEED TO GET VACCINATED?Yes. All biologics (etanercept, adalimumab, infliximab, ustekinumab, secukinumab, brodalumab, ixekizumab, guselkumab, tildrakizumab, risankizumab, bimekizumab) (and apremilast), as well as the other anti-inflammatory drugs prednisone, ciclosporin, and methotrexate, are immunosuppressive. This means that if you use one of these medications, you are classified as "patients with reduced resistance to infections" and are eligible for the flu shot. The current recommendation is: get vaccinated as soon as the vaccine is available.
If you use these medications, it is wise to contact your GP to inquire whether their records indicate that you are a "patient with reduced resistance" eligible for the flu shot.
The same applies to the COVID-19 vaccine: get vaccinated as soon as you are eligible.HOW MUCH DOES TREATMENT WITH BIOLOGICALS COST?
| Brand name |
substance name |
dosage |
annual price |
| Enbrel |
etanercept |
25 mg twice a week |
€10,393.- |
| Enbrel |
etanercept |
50 mg twice a week |
€17,090.- |
| Benepali |
etanercept |
50 mg twice a week |
€16,453 |
| Bimzelx |
bimekizumab |
1 x every 8 weeks |
€18,034 |
| Humira |
adalimumab |
1 x every 2 weeks 40 mg |
€9,919.- |
| Kyntheum |
brodalumab |
1 x every 2 weeks 210 mg |
€17,913.- |
| Ilumetri |
tildrakizumab |
1 x every 12 weeks |
€19,615.- |
| Inflectra |
infliximab |
1 x every 2 months 5 mg/kg |
€13,024 |
| Remicade |
infliximab |
1 x every 2 months 5 mg/kg |
€13,143 |
| Remsima |
infliximab |
1 x every 2 months 5 mg/kg |
€12,179.- |
| Skiryzi |
risankizumab |
1 x every 12 weeks |
€19,995.- |
| Stelara |
ustekinumab |
1 x every 3 months 45 mg |
€15,844.- |
| Stelara |
ustekinumab |
1 x every 3 months 90 mg |
€15,844.- |
| Cosentyx |
secukinumab |
300 mg once every 4 weeks |
€19,844.- |
| Taltz |
ixekizumab |
1 x every 4 weeks |
€20,284.- |
| Tremfya |
guselkumab |
1 x every 8 weeks |
€18,063 |
| Otezla |
apremilast |
30 mg twice a day |
€8,563.- |
|
