Is it safe to have biologics for Ankylosing spondylitis ?

Biological drugs or biologics in Ankylosing spondylitis are reasonably safe . These biologics have dramatically changed the way we (Rheumatologists) treat many inflammatory arthritis, especially rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Millions of arthritis patients world over have had life changing experiences with these drugs.

Everything about Ankylosing spondylitis : Basics for patient

However, like all drugs, they have potential side effects. The problem is when an Ankylosing spondylitis patient reads a side effect leaflet of any biological drug, they become really concerned about same. Many patients feel that all these drugs have serious side effects and do not take these drugs. They do so even if their diseases is very severe and these drugs will help them.

The purpose of this article is to decrease patients concerns about this drugs and help them understand few things in more detail. When they have better knowledge, patients can make better decisions about safety and proper usage of these biological drugs.

We are not going to mention list of side effects given on leaflets of these drugs, but here are the links (Link 1 , Link 2). One can have a look at possible side. We have given two links, but most drugs will have a similar leaflet. The drugs approved for use in Ankylosing spondylitis are following (real drug names with brand names mentioned in bracket) :

The drugs which act against anti TNF molecule in body and known as anti TNF drugs (There are 5 anti-TNF drugs)

Infliximab (Remicade, Infimab),

Adalimumab (Humira, Exemptia, etc),

Etanercept (Enbrel, Intacept, Etacept etc)

Golimumab (Simponi),

Certolizumab pegol (Cimzia),

&

Anti IL 17 class of drug (acts against anti IL17 molecule in body)
Secukinumab (Cosentyx, Scapho).

When do we advice and why do we use biologics in Ankylosing spondylitis ?

The details of what is ankylosing spondylitis and how it affects body are mentioned in this article here. Please read it thoroughly before going ahead with this article.

In short, we recommend biologics in Ankylosing spondylitis in various possibilities as mentioned below

• Patient having continuous pain and inflammation as seen by MRI or by very elevated CRP and ESR. All these leads to patient having very poor quality of life.
• Patient has a lot of pain in the hip or groin area and there is a lot of inflammation in hip. Hip joint can get damaged if not treated. The hip-joint once damaged might need replacement.
• If there is a lot of inflammation, it will lead to damage and spine deformity as we have shown in the detailed article in link above.

Explanation about each side effect and safety of biologics in Ankylosing spondylitis (Please read the links 1 and 2 as above to look at side effects and we will try to explain each of them in more detail from patient’s perspective)

• Allergic reactions :

The leaflet mentions that one can have serious and life threatening allergic reactions. Though minor skin rashes, mild itching etc may be common, a serious allergic reaction is very rare. We usually recommend taking first injection under somebody’s supervision and usually there are no issues. Some drugs are given as IV infusions and given in a proper clinic with arrangements for any issues. If somebody has a severe allergic reaction to one drug, in most cases we stop that and offer them another type. Also, some patients can have minor issues like any other drug. These usually are not troublesome and disappear once body gets used to the drug.

• Skin diseases

In some patients these drugs (anti TNF drugs) might give a Psoriasis skin disease like or other rashes. Funnily, we actually use these drugs for Psoriasis. These just shows that body can be unpredictable. In any case, this is not serious and things usually reverse when we withdraw the drug.

• Cancer risk with biologics in Ankylosing spondylitis

Everybody fears this word the most. Now one would think that it if foolish to take an arthritis drug with possibility of cancer. To explain in short, TNF and IL17 have some protection role against infections and cancer in body. We had this fear that if we inhibit these molecules to treat Ankylosing spondylitis, it might increase cancer risk in the body. But we have enough evidence that we should not fear too much of this risk for reasons given below :

• All drugs approved in humans undergo rigorous trial for at least 10 years, starting with animals, later some humans and later multiple humans, before being approved. Government authorities approves them only if their safety in the patients is higher than any possible side effects.
• We said that TNF and IL17 molecules protect us from cancers and we are inhibiting them. However, human body is very complex. At any point there are thousands of things happening in body to prevent cancer. Just inhibiting two molecules do not dramatically increase cancer risk.
• We have used at least anti-TNF drugs for around 20 years now. There has been no evidence to say that it increases the risk of cancer more than usual risk in such type of patients. There will be always cancer occurring in some people as it does occur in life. It doesn’t mean the drug caused it. Biological drugs are also used in patients with Rheumatoid arthritis and Inflammatory bowel diseases. These diseases in itself have slightly higher chances of cancer. That doesn’t mean taking biological drugs makes it more than the usual risk.
• In theory even if there is a very small risk which is impossible to predict, the risk of not taking these drugs is much higher. One can have lifelong pain, very poor quality of life, spine deformity and hip-joint damage requiring replacement without these drugs.

We are not saying that chances of these drugs playing some role in cancer is zero. What we are saying that even if it is present, it is extremely small, impossible to pinpoint to drug and no evidence for same has been seen after 5-20 years of use of these drugs (specially for anti TNF drugs. Cosentyx or Secukinumab or Scapho has been around for three years).

• Risk of serious infections (other than Tuberculosis) with biologics in Ankylosing spondylitis

If you read the leaflet there is risk of serious infections mentioned in it. We will explain this in detail. We have already mentioned AS is like an autoimmune disease and we treat it with drugs which tries to control overactive immunity. Because we try to control some part of immunity which helps fights infections, there is a potentially increased risk of infections.

• The risk of serious infections, except for Tuberculosis (TB), is 1 in 1000 to 2000 on an average per year of use of this drugs. Again body is very complex and immune system has many components which helps body fight infections. The biological drugs in AS target very specific molecules. As mentioned for cancer, even if somebody is on biologic drug, there are still many things going in body to prevent one from infection.
• We check patients for evidence of infections like Hepatitis B, C and HIV before starting treatment.
• The risk of infection also depends on hygiene, one’s background health (whether they are on steroids, do they have diabetes or other disease etc). Generally speaking, ankylosing spondylitis patients are relatively young and healthier as compared to Rheumatoid arthritis patients and hence have a lesser risk of infection on biologics.
• We generally advice patients to take some vaccinations and be careful about any symptoms of infections. We also promote eating and living healthy, about good hygiene and hand washing.

• Risk of Tuberculosis with biologics (specially anti TNF drugs) in Ankylosing spondylitis

Tuberculosis is a major problem in most Asian and African countries like India (those with high incidence of TB) . Biological drugs especially, Anti TNF class of drugs can increase risk of acquiring TB by 3-5 times in a patient. People in these countries are already at higher risk of TB compared to people in developed or western countries. So this poses a significant risk of TB in patients going on biologics in these countries. This risk can vary from 1 in 50 patients to 1 in 250 patients depending on many factors.

How do we tackle this and decrease the above risk of TB ?

• We take a detailed history of patients going on biologics. All people in high TB incidence countries like India, have been exposed to TB bacteria at some point in their life. Many might have had TB some time. Many have had prolonged contact with family member with TB. We ask all that.
• We check patients for evidence of silent TB bacteria in the body. We check their X rays, CT scan, history and so some specific blood tests. We call this ‘latent TB infection’. This basically means that patient has some evidence of TB bacteria silently sitting in the body. If we give drugs like anti TNF or other biologics in these patients, there is a chance that these silent TB bacteria might become active and give one full-blown TB. This usually happens during first year of biologic therapy.
• If we find that somebody has evidence of ‘latent’ or ‘silent’ TB bacteria, we give these patients anti TB drugs for at least 4- 8 weeks before starting biological therapy. This whole precautionary method significantly reduces the risk of one having TB on these drugs. We also continuously monitor patients on biologic drugs for any evidence of TB and hold these drugs if somebody develops TB.
• In most patients, these drugs dramatically change their quality of life. Most such patients are happy to take this risk of TB as long as they are properly explained and undergo investigations as above. We are continuously finding new ways of preventing TB in such patients whilst on these drugs and we are getting better.
• There has been decent evidence that Secukinumab (anti IL17 class of drug – brand name Cosentyx / Scapho) doesn’t increase risk of TB in Ankylosing spondylitis patients like anti TNF class of drugs. It might be a better option in high risk patients, but evidence at this moment is preliminary as the drug has been around for far lesser period compared to anti TNF drugs.

• Liver problems / jaundice : Patients with hidden hepatitis B or C infection – a kind of liver infection can become active while on biologic drugs. We actually check patients for Hepatitis B or C infection before starting treatment in such patients and take measures to prevent its activation.
• Heart failure: We avoid giving anti-TNF class of drugs in patients with weak heart or risk factors for same. There is some evidence that it makes heart pump less in patients with preëxisting heart disease eg : patients with history of heart attacks. The biologics do not as such directly affect heart or do not give heart attacks. This is again hardly an issue if we carefully select proper patients.
• Nervous system problems / Demyelination : We avoid anti TNF drugs in somebody who already has neurological diseases like : demyelinating disease, multiple sclerosis. These are uncommon diseases and usually ankylosing spondylitis patients do not have it. Biologics are not known to cause any major neurological disease as such. They can only worsen above diseases.
• SLE / Lupus / new autoimmune disease risk – Systemic lupus erythematosus – SLE is a another disease treated by rheumatologists. Funnily, when we give anti TNF biologics in patients with AS, RA etc, sometimes some patients might develop a form of SLE / lupus. This just shows that body is very complex and sometimes we can’t control everything. We call it ‘drug induced lupus’. But again, this is very uncommon side effect and in most cases the this new disease of lupus is mild and is reversible when we stop the drug responsible.
• Unpredictable issues – Despite taking all precautions, some patients on these drugs always come with issues which can never be directly related to drug. We talk to such patients, go through everything and collectively take a decision to continue or not continue the drug.

So, what precautions to take when one is taking or planning to take a biologic drug for Ankylosing spondylitis ?

• If one is taking biologic drugs for Ankylosing spondylitis, make sure that you are takin it under Rheumatologist advice. Only Rheumatologists have training to assess which patients need biologics and make sure to take all the precautions.
• Take vaccines as advised by rheumatologist.
• Eat and live healthy, wash hands properly when needed. Keep proper hygiene. Avoid eating food from sources which have high chances of infections (eg : roadside eateries, stale food, partly cooked or uncooked food etc).
• Avoid exposure to patients with infections unless necessary. Prolonged exposure to any person having cough and TB needs to be avoided until they have started proper treatment for at least 2-4 weeks.
• Before starting treatment -You should let your doctor know if you have or ever had any of the following:
  
  • Tuberculosis (TB) or have been near someone who has TB.
  • Lived in a region where certain fungal infections like histoplasmosis or coccidioidomycosis are common.
  • Infections that keep coming back, have diabetes or an immune system problem.
  • Any type of cancer or a family history of cancer
  • Heart failure or any heart condition.
  • Hepatitis B or C virus (HBV) infection
  • Nervous system disorders (like multiple sclerosis or Guillain-Barré syndrome).

You should tell your doctor right away if you have any of the signs listed below:

• Infections (like TB, blood infections, pneumonia)—fever, tiredness, cough, flu, or warm, red or painful skin or any open skin wounds.Hold injections until you talk to a doctor during or if you think you have infection.
• If you are found to have any cancer
• If you develop breathing problems, leg swelling, chest pain etc indicating some heart issue
• Liver problems—jaundice (yellow skin and eyes), dark brown urine, right-sided abdominal pain, fever, or severe tiredness.
• Nervous system disorders—numbness, weakness, tingling, changes in your vision or fits/ seizures.
• Any new skin rashes
• Anything which cannot be explained by simple things and makes you feel that it could be something due to drug you are taking

To summarise,

• Biologics in Ankylosing spondylitis patients are reasonably safe if taken under proper guidance and review of a Rheumatologist
• Biologics are often prescribed to AS patients when we feel that without them they will have persistent pain, poor life quality, poor functioning capabilities, hip-joint or spine damage.
• Minor side effects can be easily tackled and most moderate side effects are uncommon and can be reversed on stopping the drugs. Some side effects are impossible to predict as every person is different and it is best to talk to one’s own doctor for review of same.
• The risk of cancer with biologic drugs remains theoretical or very little at best. Recent evidence for anti TNF drugs have been very encouraging and no increased risk has been seen for most major cancers even after 20 years of use. Though theoretically possible, the risk appears to be far lesser than benefits. Continued monitoring is essential.
• The risk of serious infections, especially TB is real with biologics. TB risk is a major concern especially in patients on anti TNF drugs, especially in developing countries like India (and many other Asian and African countries with high TB incidence). Rheumatologist carefully goes through this risk with history and tests and helps one prevent having TB. This risk however cannot be completely taken away. Secukinumab may be a safer drug with regards to TB compared to anti TNF class of drugs. Again continued monitoring with Rheumatologist while on drug is essential and reporting any new problems is important.

If you have any doubts, do not hesitate to contact us. We try to respond within 48-72 hours.