Biologics (mAbs) - what are they and how do they work? 🤔

[EmmaF91]

Hi everyone - hope you are well. Thought I’d cover a commonly asked about thing today for the severe asthmatics! I KNOW this infomercial will be a long one so let’s get started! 😂

WHAT IS A MAB?

First thing to note it that the words biologics/biologicals and mAbs are used interchangeably 😂. They are referring to the same thing! Here’s a quick explanation behind the names!; Biological drugs are sometimes referred to as biologic response modifiers (BRMs) because they change the manner of operation of natural biologic intracellular and cellular actions. Monoclonal Antibodies (mAbs) are are created to specifically target specific cells/parts of cells and to modify disease processes. In asthma, they are designed to target parts of the process that causes the immune system to turn against itself and attack the body when it shouldn't! The drug names all helpfully end in -mab too 😉. There are hundreds of different types that do different things but at the moment there are 4(.5) available in the uk for asthma that I’ll go into later 😉. Unfortunately there is nothing yet available for our non-allergic, non-eosinophilic brethren so hugs to all of you who are severe and unable to access mAbs at this moment in time... hopefully one day soon!

WHO CAN GET BIOLOGICS?

Each MAB has its own specific criteria, but in essence it’s; not smoking, having a ‘count’ high enough for the specific bio you want, a recent history of exacerbations, or long term steroid use and are on maximum optimal therapy available without the bio. If you are on a biologic you are classed as having severe asthma. In England, they can only be prescribed by a tertiary ‘asthma specialist’ hospital, however I think in Wales and Scotland things may be different 🤷‍♀️ (let me know below!). The other thing to note is that in Scotland some of them aren’t available and others require lower scores. Just a note (as not ALL doctors are aware), steroids can falsely lower BOTH IgE and eosinophil count. They are there being produced etc, but are masked. So if you had a low count whilst on 20mg+ steroids that may be the reason why, so it’s worth reasoning for when your steroid dose is lower. And yes this does lead to a catch 22 in some people - need a mAb cause you’re poorly but too poorly to come off pred to show you need the mAb! If you’re recommended for a mAb, it is not a 1 person decision. In England (again Scotland and Wales may be different, I don’t know so please comment below of it is!), they will take your case to a MDT (multidisciplinary team meeting) for discussion and then need to get funding approval. It may take up to a month to get your first dose once a spec doc is certain you should get it.

ALLERGIC/ATOPIC ASTHMA

This can be caused by having a high IgE. IgE stands for immunoglobulin E which a type of antibody. Antibodies are made by the immune system to protect the body from bacteria, viruses, and allergens. IgE antibodies are normally found in small amounts in the blood, but higher amounts can be a sign that the body overreacts to allergens. This can lead to an allergic reaction. People with a high IgE typically have allergic asthma (but not everyone with allergic asthma necessarily has it IgE driven).

OMALIZUMAB/XOLAIR

Xolair blocks the action of IgE which then hopefully causes less allergic reactions. A score over 30 can be classed as high enough for xolair, however if your score is too high (over 700 - weight dependant in adults, over 1300 in kids again weight dependent), it can also make you ineligible. If you want see the specifics google image ‘xolair chart’ and make sure you check out the 12+ age group one 😉😂. They will work out dose/eligibility using your HIGHEST IgE count in the last 6 months.

Depending on weight:levels ratio this can be either fortnightly or monthly, and the dose also changes. This is a subcutaneous injection(s), meaning it gets injected to just under the skin. Depending on the dose required, you may have up to 3 (I think) injections each time. It is licensed for patients from the age of 6 on 4+ steroid doses a year, on max therapy. Xolair also treats chronic idiopathic urticaria, obviously with different criteria 😅. However for the Scots among us, this is one you can’t access for asthma (however you can for urticaria)

EOSINOPHILIC ASTHMA

Eosinophils are a type of white blood cell, which are made in bone marrow. They can do many things like help fight bacteria and parasites and kill dying cells but in asthma it’s more concerning that they participate in allergic reactions, play a part in inflammatory responses and “respond” to areas of inflammation. If you have too many eosinophils (ie produce a lot all the time) they can ‘attack’ your lungs causing asthma which is not allergic. According to asthma UK about 40% of severe asthmatics have eosinophilic asthma.

MEPOLIZUMAB/NUCALA

In England this is typically the first eos mAb you’ll be put on. Mepo works by blocking interleukin-5 (IL-5) which is responsible for the maturation and release of eosinophils in the bone marrow. This means your body doesn’t produce eosinophils, and thus they can’t attack your lungs 😉. To be eligible for this drug you need to be over 12, have a blood count of 0.3 in the prev 12 months, be on max home therapy AND had either 4 pred courses in 12 months OR been on 5+mg/day of pred for 6 months. In Scotland you only need a count of 0.15 tho the other requirements are the same. This is a 4 weekly subcutaneous injection, and it is only 1 injection as it’s the same dose for all!

RESLIZUMAB/CINQAERO

For resliz you need to be over 18, have an eos count of 0.4 and have 3+ exacerbations needing steroids/increased steroids in the last year. Like xolair this is not available in Scotland. Resliz also binds on to IL-5 like mepo to prevent eosinophil production. It is given once every 4 weeks via IV infusion over 20-50 minutes, dose depending on weight.

BENRALIZUMAB/FASENRA

Whilst mepo and resliz work by preventing eosinophil production, benra works by attaching onto the eosinophil and destroying it. It cannot differentiate between eosinophils and basophils (another type of white blood cell) so attaches to both. Benra is licensed for adults on max therapy, with an eos count of 0.3 and had 4 or more exacerbations steroids in the last year OR 5+mg/day pred for 6 months, OR an eos count of 0.4 with 3 flares in 12 months that needed steroids. In Scotland the requirement is 0.15 and 4+ flares needing steroids OR 6 months of 5+mg/day steroids. It is a subcutaneous injection, for the first 3 weeks 4 weekly, then after that 8 weekly.

COMING SOON - DUPILUMAB/DUPIXENT

Still undergoing NICE approval for the treatment of asthma, so is only available in some areas in England (maybe UK??) under the early access program. It works by inhibiting interleukin-4 and interleukin-13 signalling. IL-4 and IL-13 together play a part on activating eosinophils and IgE, and should help decrease the type 2 inflammation in the lungs that appears in atopic and eosinophilic asthma. It is currently licensed in the uk for moderate-severe atopic dermatitis (eczema). It is a fortnightly subcutaneous injection, with the initial dose being double the maintenance dose (so the first dose consists for 2 injections). So far there’s been no eligibility provided for this drug in the UK for asthma, but their marketing says it’s for ages 12+ on max therapy, with both raised eos and raised IgE.

COMMON SIDE EFFECTS

The asthma mAbs tend to all give similar side effects so I thought I’d lump them all together here. Some are more likely than others in general, or more prevalent in a particular mAb. This is not a comprehensive list in any way, but covers the most common and/or the most important to be aware of even if unlikely!

Injection site pain, redness, small bruise/hive, stinging/burning sensation

Headaches/migraines, muscles aches and weakness, fever, abdominal pain, back pain, dizziness, drowsiness, fatigue,

Increased risk of infection (usually helminth injections)

Eczema, nasal congestion

Hypersensitivity reactions (anaphylaxis, angiodema, urticaria) - anaphylactic is is rare but common enough for the observation being needed for the first few doses (this is why you’re normally told to hang about for up to 3hrs post stab, and warned that it may happen. Some mabs have a higher likelihood than others. All mabs have a different waiting time. Those on self-administration should be aware of this).

WHAT IF I’M ILL?

If you are unwell when your injection is due contact your team before you attend. Some mAbs (and some clinics) do not recommend giving the injection of an active infection is going on, and so they may reschedule. Better to get confirmation of this BEFORE you make the effort to go in 😉😅. If it’s rescheduled don’t worry, they’ll get you in as soon as they can and then get you back on track. If it isn’t rescheduled don’t worry 😉, it just means the team are confident that it’s ok with the bio you are on!

STAYING ON YOUR MAB

Most (if not all) the mAbs have a 12 month check in and reassessment. Here they will assess basically how much the drug is working, and to make sure it’s cost effective. Normally to measure this they will look at if you’ve managed to come off/stay off/lower (to AI level only) steroids successfully. HOWEVER, if you can prove cost effectiveness a different way they should take that into consideration. So if you were constantly in and out of hospital, but now can manage at home with steroids, that shows that it’s saving them money that way. If you can show how admissions have reduced, become more spaced out, been triggered by things not treated by the bio you’re on or been shorter with less drugs to get you to a better place then they should listen. Also discuss how much it’s affected your QoL. Steroids is an easy baseline for them to aim for, but for some that’s an unrealistic aim, so show them other ways that it is helping that they can measure! If it’s not working for you, the doc may discuss switching you to an alternate bio to see if that helps more!

Hope this helps anyone who is in the process of getting on to a bio. And as I said, our Scottish and Welsh buddies please let me know if anything is different where you are!

Hopefully soon I’ll do a post about the common (and not so common 😉) asthma add ons, and maybe another about comorbidity add ons (depends how long the add ons post gets 😳😂). Stay safe everyone

[Claire-Rose]

I’m on Xolair have had 3 so far and I have noticed the difference i use to be on 50mg pred and struggled to get pass 40 and now I am on 35 and feel amazing still, honestly I don’t know what I would do without it which is why I’m so surprised it’s not available in Scotland

[Pipsqueak77]

Hi

Useful post...👍

In my clinic Benralizumab is first line bio for high eosinophils ... so people already on Mepo can stay on it if they choose but it’s not cons first choice any more.

Also there are several people already on Dupilumab at clinic - people who have had no luck with Mepo/Benralizumab so not sure of criteria but it is in use in England already.

Take care 👍😊

[EmmaF91 Community Ambassador in reply to Pipsqueak77]

Yeah. It’s something that’s changing. Last year mepo was everyone’s first line due to NICE criteria (as benra spent half the year as early access). Now docs can choose whichever but a lot have got stuck on mepo as first line 🤷‍♀️😂.

Dupil is in use in England but it’s early access only. So only some spec hosps (ones connected to research) have access to it not all. Once it’s NICE approved there will be criteria available. Last year I accessed benra on the early access program so started it in May when I don’t think it was approved til June/July.

[JustR]

Really useful..thanks for taking the time to explain.

I’ve tried Xolair and it wasn’t for me.

I’ve had regular bloods since but not in range for Mepo but I know I’m not going to be as I’m now steroid dependant. Can’t get lower than 10mg and my consultant wants me to get to 5mg as thinks this will help be in range🙈like I haven’t been trying for the last 18months.

I really feel stuck now..I can’t see this next biologic happening anytime soon..if at all?

I’ve asked the question about qualifying on the basis of being on long term pred but he’s saying he needs the bloods to be in range to support my case😕

[EmmaF91 Community Ambassador in reply to JustR]

Yeah. Unfortunately you need the number and the history to be eligible for things. Dupil is on its way. But it’s in early access at the moment, and I don’t know what criteria is needed for that (or what it’ll be when it’s approved).

Sorry to hear that xolair wasn’t for you. Hopefully you’ll find something that helps soon (or at least get the scores to try something else)

[JustR in reply to EmmaF91]

I tick all other boxes but can’t get my numbers when I need them!

Going to try and stay positive but like you said..my quality of life has changed so much in the last 2years..Had to stop working..struggle to run around after my two young children..but I’m still going to stay positive and determined!

Thanks again for the information!..you’ve explained better than my asthma team🙌

[Celie1]

Hi Emma, hope you are well.

I was just reading your post with interest (must admit some of it went straight over my head!😳😂) I was curious about Allergic asthma. If the ‘allergic’ asthma is not driven by IgE, then what is it driven by?

The reason I’m curious is that I think I have allergies, i.e. I have a runny/blocked nose all year round. I had a long period of time (but not so much now), when if I came into contact with any sprays, perfumes, flowers, fumes, cleaning products, long list... it would send me straight out of the room unable to breathe properly and reaching for the ventolin. The effects of this could last all day and I couldn’t go back into the area where the problem was and often had to go home from work.

I had a blood test (not sure what it was but think it was the IgE) which came back negative. My asthma nurse said at the time, it was just a personal response. 🤷🏻‍♀️😏 Confused! At the time I didn’t know enough about asthma or what was happening to me and no one really explained, so it came back to me as I read your post. So if I had (then) an ‘overreaction to allergens’ why didn’t my body produce antibodies to fight these? Hope this isn’t too confusing and you could explain a bit more. 😬😊

[ccccc in reply to Celie1]

Hi Celie1 and Emma

I have recently started Xolair (had two doses and have started to feel better and due to have two more at least when they re-assess). I was told my Fev1 had to be below 80% and I had to be taking long-term steroids, which I am now. Luckily my Fev1 went below 80% on the day of the spirometry at the hospital (it's hovered just over 80% for a few years.) It has taken me 6 years and three different hospitals before getting this treatment. I have severe allergic asthma but my IgE isn't too bad (about 90) even though I have terrible trouble with pollen, moulds etc it doesn't show up apart from a raised response to mould in my blood tests.

I get the strong impression there are some respiratory consultants who have a lot of confidence in Xolair and other Mabs and some who don't - the ones I used to see lowered my sights immediately at the first appointment by saying they "weren't the panacea they thought they'd be" - so just stuck me on steroids! - then when I got referred to my current hospital straight away they were singing its praises and were happy to make a case for funding. So what I'd say is - keep pushing and keep trying to find the right hospital team for you rather than just accept being stuck on steroids (I have developed osteopenia and low cortisol as a result of them) as not everyone fits into neat little diagnostic boxes when it comes to asthma.

[Celie1 in reply to ccccc]

Hi, that’s interesting about your IgE level. How did they identify you with ‘severe allergic asthma ‘ ?Was it based on your reaction/symptoms rather than the IgE blood results?

I’m glad you managed to get a treatment that works.😊 it must be a relief after all that time.

I’m beginning to realise I don’t fit into a neat box at all! 🤦🏻‍♀️But I am ready to push if I need to with everyone’s help and advice on this forum 😁

[ccccc in reply to Celie1]

Hi Celie, it seemed to be on the basis of the initial appointment with the new hospital where I told them what triggers my asthma plus the results of the blood tests they did which showed raised reaction to moulds especially Aspergillus. That proves my theory, as they didn't find anything I hadn't heard before except they treated it as 'severe allergic asthma' whereas at the other hospital it was just plain old 'severe asthma'! But I've had scratch tests before which showed no reaction at all to pollen, so some tests aren't always reliable, it can often come down to how you are on the day.

My IgE used to be up around 500 10 years ago but I was put on Montelukast which decreased the IgE number but I didn't feel any different - my asthma still felt just as bad - and I've had to rely on heavier doses of steroids since. What's changed is the new team are much more open-minded about this disparity whereas the old team had the mentality of just going off the numbers and not pushing for Xolair rather than considering how it affected me - I'm basically house bound for the summer months, can't take holidays as my asthma gets much worse when I come into contact with various types of pollen. So, yes, I do agree there are protocols to be met in terms of the funding for Mabs but I also think it's a question of attitude among the consultants who are treating you. I also think some consultants just aren't well informed about Mabs, which I know Asthma UK are campaigning to change, so if you aren't getting any luck maybe try a different hospital (usually the big regional ones, also called tertiary centres, tend to be better at treating less typical cases).

The past 10 years I've had everything from being told by one consultant at the first hospital I was under he could see a day where I wouldn't need any asthma medication at all (bizarre considering it's a chronic illness I've had for 35 years...) to finally getting Xolair. Some are excellent, some of them talk utter garbage I'm afraid! If what they say doesn't tally with your experience of your asthma then trust your instinct and try elsewhere. Maybe contacting the Asthma UK nurses on the helpline might help too as they are brilliant. Good luck and always ask around the board here for help👍

[Celie1 in reply to ccccc]

Hi, thanks for the detailed reply.😁

My symptoms are nowhere near as bad as yours, especially now I’ve retired and can keep away from environments which I know will trigger my asthma. My sensitivity to perfumes, aerosols, etc are a lot less now because I’m not being bombarded on a daily basis with all the different irritants I think.

I don’t know how you cope staying in through the summer 😳It’s really weird and frustrating that these allergic reactions we have don’t always show up on allergy tests 😤. As you say it can depend on the day.

It’s good to know there are consultants around who do think outside the box, we just have to find them 😆. Also good to know we can always find support on this great forum 😍. I have spoken to the AUK nurses a couple of times too - they’re so helpful.

Good luck with your ongoing treatment. Hope it continues to help 😁🤞

[ccccc in reply to Celie1]

Thanks Celie it's frustrating when how you feel isn't reflected in the various tests etc, sadly avoidance is often the only treatment (which is hard in a world of pollen, chemicals etc!) take care also x