How Do Biologics Work to Treat Autoimmune Diseases?

Before cytokines can produce inflammation, they need to attach to receptors on the surface of your cells. Think of it as opening the lock on your front door with a key. You can’t turn on the lights until you unlock and open the door. Cytokines can’t affect your cells until they open the lock. Biologics prevent cytokines from unlocking your cells and causing inflammation and possible damage in a few ways. Some of these medications block¹¹ the receptors on cells so that cytokines can’t attach to them. Other drugs fill the receptor themselves, leaving no room for the cytokine.

Each biologic works against a specific cytokine. But some autoimmune diseases are fueled by more than one cytokine. So how does your doctor know which one to choose?

“We don’t really have an easy mechanism to say, ‘If I have four or five cytokines that commonly cause an autoimmune disorder…it’s absolutely this cytokine,’” Dr. Frame says. The decision comes down to which biologic most people with your condition responded well to in studies, and your doctor’s preference, he adds. Your insurance coverage, if you have it, can also factor into the decision, Dr. Husni says.

What types of biologics are there?

Biologics are divided up into groups, or classes, based on the inflammatory pathway they target⁷. Each works by preventing a particular cytokine from causing inflammation. Below are the common biologic classes used to treat autoimmune diseases:

TNF inhibitors

What they target: These prevent the tumor necrosis factor protein from binding to its corresponding receptors and causing inflammation⁸.

Autoimmune diseases they commonly treat: ankylosing spondylitis, Crohn’s disease, ulcerative colitis, psoriatic arthritis, rheumatoid arthritis

IL-1 inhibitors

What they target: interleukin-1, interleukin-6, interleukin-12, interleukin-23

Autoimmune diseases they commonly treat: juvenile idiopathic arthritis

IL-6 inhibitors

What they target: interleukin-6

Autoimmune diseases they commonly treat: giant cell arteritis, juvenile idiopathic arthritis, rheumatoid arthritis

IL-17 inhibitors

What they target: interleukin-17

Autoimmune diseases they commonly treat: psoriasis, psoriatic arthritis, ankylosing spondylitis 

IL-12 and IL-23 inhibitors

What they target: interleukin-12, interleukin-23

Autoimmune diseases they commonly treat: psoriasis, psoriatic arthritis, Crohn’s disease

B-cell inhibitors

What they target: B cells

Autoimmune diseases they commonly treat: rheumatoid arthritis, lupus

T-cell inhibitors

What they target: T cells

Autoimmune diseases they commonly treat: rheumatoid arthritis

How do I take biologics?

Biologics are very sensitive to the acid in your stomach and can’t be taken orally like many conventional medications. “If you try to give most of these biologics orally, they will mostly be chewed up by the stomach acid,” Dr. Frame says. “We have to give them either through an IV directly into the blood or injected under the skin,” he says.

How often you need treatment and the way you receive it depends on your type of autoimmune disease, and which biologic you take. For example, some medications can be self-administered through an injection under your skin weekly. Other drugs are given through an intravenous infusion monthly or every few months.

What about side effects?

Any drug you take can cause side effects, and biologics are no exception. It’s common to feel tired for a couple of days after your infusion or injection, or to have headaches. Other side effects of taking a biologic include reactions near your injection site, a mild sore throat, and stomach pains.

Biologics: Basic Facts for Patients

People with inflammatory autoimmune diseases, such as rheumatoid arthritis and ankylosing spondylitis, may be prescribed biologic drugs if traditional NSAIDs (e. g. ibuprofen) or DMARDs (e.g. methotrexate) are ineffective. Biologics can also be used in conjunction with these traditional medications.

See 5 Types of Medication That Treat Rheumatoid Arthritis (RA)

How Biologics Work

Before symptoms of inflammation can be seen or felt, a series of biochemical reactions takes place in the body. A biologic drug targets and prevents a specific reaction from happening, stopping the inflammatory process in its tracks.

In contrast to biologics, conventional drugs treat general inflammation (and resulting symptoms like joint pain) after it has begun.

See Pain Medications for Arthritis Pain Relief

One type of biologic: TNF inhibitors
Protein molecules called tumor necrosis factor (TNF) trigger unnecessary inflammation in people with autoimmune diseases such as rheumatoid arthritis. Biologics called TNF inhibitors contain special protein molecules that, when injected into a patient’s bloodstream, attach to the TNF molecules. When TNF inhibitors attach to TNF, the TNF cannot trigger inflammation.

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Biologics Take Time to Work

A patient may notice a decrease in symptoms as soon as 1 week or as long as 12 weeks after starting a biologic, and symptoms may continue to improve for months afterward. For example, many people who take TNF inhibitors feel symptom relief in 2 to 4 weeks, though the full effects of the drugs usually take 3 to 6 months.

It is not unusual for a biologic to become less effective over months or years, as a person’s immune system develops antibodies to the drug. When this happens, a person will notice symptoms gradually coming back. When a biologic loses its efficacy, a doctor may recommend switching to another biologic.

In This Article:

• Biologics: Basic Facts for Patients

• Risks and Side Effects of Biologics

How Biologics Are Given to Patients

Most biologics are liquid medicines administered to a patient by either:

• Injection under the skin. A patient may give him or herself injections at home. In some cases, a family member or other caregiver may give the injections.
• Infusion into the blood stream. This is typically done in a medical office and can take a few hours.

Pharmaceutical companies are working to develop biologics that can be administered with oral pills. The first of these is tofacitinib, sold as Xeljanz, which was approved by the FDA in 2012.

See The Science Behind Biologics

How often a person takes a biologic varies. In general, infusions may be needed once every 4 to 6 weeks. Injections are usually required every week or two.

Storing and Handling Biologics

Every biologic will have storage and handling instructions that must be followed, or the drug will lose some or all of its effectiveness. Most biologics should not be:

• Exposed to rapid temperature changes. For example, do not use a heat source to warm up a drug that has been stored in the refrigerator. Let it gradually warm to room temperature before injection.
• Exposed to multiple temperature changes. For example, people are advised against storing a biologic in a refrigerator, then warming it up to room temperature, and then putting it back into the refrigerator for later.
• Shaken. Rapid shaking is usually not necessary and may be harmful.

Why are guidelines like these necessary? Most medications are made up of small, stable molecules—aspirin molecules have just 21 atoms—but biologics are made up of huge molecules with thousands of atoms. The chemical bonds that hold those atoms together are relatively weak, and they can be broken by rapid temperature changes and other factors. A drug will not work as prescribed if too many if its molecules’ bonds are broken.

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Examples of Biologics Available Today

Biologics are categorized by what part of the inflammatory process they target.

See Biologics for RA and Other Autoimmune Conditions

TNF blockers are the most common type of modern biologic. TNF blockers include but are not necessarily limited to:

• certolizumab (Cimzia)
• etanercept (Enbrel)
• adalimumab (Humira)
• infliximab (Remicade)
• golimumab (Simponi)

Examples of other biologics (and their mode of action) include:

• tocilizumab (Actemra), targets the interleukin-6 pathway
• anakinra (Kineret), an interleukin-1 receptor antagonist
• rituximab (Rituxan), a CD20-directed cytolytic antibody
• tofacitinib (Xeljanz), first in a class of treatments RA called Janus kinase (JAK) inhibitors

These list change as the FDA approves new drugs and they are introduced to the US market.

See Biologics, Biosimilars, and Interchangeable Biosimilars—What is the Difference?

Cost

Biologics tend to be expensive. For example, a month’s supply of Humira (two doses) can cost around $2,000 without insurance. Some patients may be eligible for coupons and discounts through pharmaceutical companies.

Dr. Kathee de Falla is a licensed and certified pharmacist. She has more than a decade of experience providing medical advice and supplying prescription medications in a retail setting. Dr. de Falla spent several years developing drugs at Abbott Laboratories, a pharmaceutical company where she holds a patent for a drug formulation.

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Biological economy: how bio-preparations for crops work

Biologization is a new trend in agriculture, the essence of which is to care for the environment and use bio-preparations instead of conventional ones. This is an integrated approach that allows you to increase productivity while reducing production costs.

The main methods of improving soil fertility during biologization are the introduction of organic fertilizers and microbiological preparations into the soil. This also includes a reduction in the use of chemical agents and herbicidal treatments due to biological agents and cultivation with special equipment.

The so-called soil microbial activators have recently become very popular. European producers claim that their products are an innovative development, but farmers know that often the new is the well-forgotten old.

First steps

Scientists from the USSR were among the first to develop special preparations. In those days, farmers often faced a shortage of fertilizers. To solve the problem, the government actively sponsored scientific research in this area, which led to the creation in 1960s of fertilizers based on nitrogen-fixing microorganisms. After 20 years, plant protection products came into use, which are now also classified as biological products.

But their century turned out to be short-lived – they were soon supplanted by centralized chemicalization, which began in the 80s. In the 1990s, state sponsorship of scientific developments came to naught. Now interest in biologization in Russia is reviving, albeit slowly. On the market

again there are drugs that work not on chemical compounds, but on live bacteria.

Two ways

Doctor of Biological Sciences, Head. Laboratory of Biotechnology of Plants and Microorganisms of the Center of the North-East. Rudnitsky Irina Shirokikh notes that the management of biological processes in agrocenoses is possible through the introduction of agronomically valuable strains of microorganisms both into the soil and into the rhizosphere of plants. Numerous experiments carried out allow us to assert that the symbiosis of microorganisms with plants is the basis of the latter’s vital activity.

At the same time, in order to ensure optimal mineral nutrition of the crop, it is important not only the amount of nutrients in the soil, but also the degree of their availability. It is bacteria and microscopic fungi that are a kind of intermediaries between the soil and the plant, and therefore, the more active they are, and the wider their diversity, the better.

The development of biopreparations that activate microbiomes is going in two directions. The first option is the use of microbes directly, which, when the drug is introduced into the soil, have a positive effect on its fertility due to biological nitrogen fixation, more active decomposition of crop and other plant residues, the formation of humic substances and the suppression of phytopathogens.

The second option is the pre-sowing treatment of seeds or already vegetative plants with bacteria that stimulate growth and protect various crops from pathogens of harmful diseases.

– In both cases, most often we are talking about preparations containing microorganisms – cellulolytics, nitrogen-fixing and phosphate-mobilizing bacteria, – the specialist notes. – These include some bacilli, streptomycetes, Pseudomonas, and so on. When these beneficial bacteria are introduced into the agrocenosis, the plant begins to “feed” them with its secretions, in which there are tasty food sources for microbes. This is how a beneficial exchange occurs: microorganisms fix nitrogen for plants, supply phytohormones and vitamins, protect against stress and pathogens.

As a result, plants can actively develop even on soils poor in nitrogen.

Irina Gennadievna added that the situation is different with phosphorus: as a rule, there is quite a lot of it in soils, but it is in a form that is difficult to digest. And many microorganisms, such as mycorrhizal fungi, phosphate-mobilizing bacteria, produce acids outside, which dissolve hard-to-reach compounds, due to which the plant absorbs phosphorus.

Another option is humic preparations, the active ingredients of which are sodium, ammonium and potassium humates. It is known that humic substances are the products of vital activity of soil microorganisms. They activate the activity of soil microflora, increase the supply of nutrients to plants, stimulate the growth and development of plants, increase their resistance to low and high temperatures, moisture deficiency, increase yield and improve its quality.

Humic biopreparations have another useful property – they are able to bind toxic and radioactive elements into slow-moving or difficult-to-dissociate compounds. The introduction of such growth stimulants into the soil increases the number of ammonifying bacteria by an average of 3-5 times, nitrifying – by 3-7 times. The ability to fix molecular nitrogen also increases – about 10 times.

– Thus, biological products of both the first and second groups, at a relatively low cost and high environmental friendliness, effectively affect the soil, contributing to a more active life exchange between plants and microorganisms, increasing productivity and maintaining soil fertility, – adds Irina Shirokikh.

Experts note that biological preparations are distinguished by high payback. This is due to their low cost and high efficiency. In addition, one drug can be used throughout the entire growing season, and its effect will manifest itself in the long term.

Measure seven times

Proper use of drugs in modern agriculture has many advantages. However, a positive effect will be only in the case of thoughtful introduction of stimulants.

– It is possible to activate the soil microflora only up to certain limits, since excessive biological activity can have negative consequences for the soil: destruction of organic matter, dehumification and deflation processes. Therefore, the use of biological products, as well as any other agricultural technologies, should be targeted and take into account the peculiarities of crop rotations, tillage systems, regional natural and climatic conditions. Not a single biological product is universal: a differentiated approach is needed in this area, – says Irina Shirokikh.

For this reason, soil biologization, including the introduction of microbial activators, is more popular in small and medium-sized farms. Within the framework of a large enterprise, the lands can be very different from each other, and therefore it is necessary to select their own preparations for each type.

In addition, the use of such preparations requires not only attention to the condition of the soil, but also work with it, since the survival of bacteria depends on this. So, some of them may simply not survive if the soil is, for example, too acidic.

Prospects

But the prospects for biological products are great. This is also evidenced by statistics – the market volume over the past 5-6 years has grown more than three times due to an increase in demand from farmers who are faced with depletion and soil pollution due to excessive chemicalization.

Biologization is developing especially actively in regions where agrarians closely cooperate with scientific institutes: in the Krasnodar and Stavropol Territories, Bashkiria, Belgorod, Voronezh, Leningrad, Tomsk Regions and in the Moscow region.

The fact that in Russia there is a good scientific base for this, laid down at the end of the last century, also plays a role in the development of biologization and the use of biological preparations. Many studies of the effectiveness of microorganisms and methods of their activation in the soil are still relevant. In the Kirov region, the issues of creation and rational use of biological preparations are successfully solved in the Federal Agricultural Research Center of the North-East and the Vyatka State Agricultural Academy.

– A smart farmer feeds not so much the crop as the soil, because this work is for the future. You won’t get a momentary

benefit, but will have a long-term positive result. Especially if we add to the use of biological products the correct system of tillage, the competent use of green manure, the introduction of manure or compost, a scientifically based crop rotation structure.

Photo: forgeforward.org, Roger Spooner/Getty Images, www. holganix.com

Biologics – Prevention or Solution? – Agroinvestor

“Bionovatik”

Biological products today should be in the arsenal of every farmer. They solve many problems in the field that were previously “cleaned up” only with the help of chemical protection

Modern biotechnology is both prevention, and a “fire” solution, and reliable protection throughout the entire growing season of agricultural plants.

This year, due to sanctions, foreign companies withdrew their products from the Russian market in the amount of more than $2 billion. But today, fortunately, there are already such manufacturers in Russia who are ready to fill the shortage with domestic microbiological preparations. Our questions were answered by the head of Bionovatik Group of Companies Rustam Rashitovich Ramazanov.

– Rustam Rashitovich, please tell us about the development of the Bionovatik company. At first there was a search for preventive solutions, then integration began (BIO + CPPP), now biological products remove those problems in the field that were previously solved only with the help of CPPP. What made this possible?

– I must say that we immediately developed not only as a production, but also as a scientific and technological company. They built a technology corporation. In 2015-2016, the first line of drugs was registered, which passed laboratory tests and fragmentary plot tests, and our entry to the market began with this line. The first product to occupy its niche was the Biodux growth regulator. It was field tested on over a million hectares at the time. It has been used in different protection schemes in different cultures. All other products of that period were intended to improve plant nutrition, and also had regulatory properties. At that time, this was a completely new direction and competence for us. At that time, they did not count on either integration with HSZR, and even less on the replacement of chemical preparations. What has been done to change the situation? They began to actively test their preparations, sold them to small peasant farms, farmers who became interested in biology, solving different problems in parallel. With each new hectare, we accumulated information, analyzed and received data on how our drugs work in practice. They have been tested on a wide range of crops. Then we focused on field crops. Moreover, not just tests were carried out – we have always involved in the testing process both science, and the agronomic service, and specialists from sales departments, distributors. Laid tests on pathogenic agricultural backgrounds. By 2018, we formed an understanding of how our biological products work, fixed their pros and cons, the threshold of effectiveness, the framework for the conditions for efficiency, temperature, humidity, climate, that is, we carried out painstaking work. We began to form the “Atlas” Bionovatika “” – a system in which complete information is structured for each crop and how chemical or biological preparations work on certain crops, what pathogens can be spread on these crops, and much more. This is done in order to give farmers the best solution for their agricultural production.

“Atlas” shows the place of our products in the market. In 2021, we have gone even further — now biological products are able to solve even those problems that chemistry cannot solve. Issues have been identified that are more effectively “removed” by biology than by chemistry, those positions have been identified where integration is possible and the best solution. The task is to find the optimal solution for the farmer. To make sure he makes a profit.

– And yet, Rustam Rashitovich, tell me, are there any plant diseases or pests on which the use of biological products will not work?

– A person in the 19th century lived an average of 40-50 years, now – 80 years. Many human diseases are now treated with antibiotics, surgically. Medicine of the XX-XXI centuries has stepped far forward. People began to live much longer. But there are still incurable diseases? Yes. Are there completely healthy people? No. You can always find certain deviations in a person, especially with age. Plants are no different from humans in this respect. The task of chemists, biologists, and geneticists is to look for solutions to those problems in plants that are expedient to solve. And there will always be unresolved questions – this is nature. Competition with nature can be endless. And in the end, she will defeat the man. Nevertheless, biology, and chemistry, and precision farming, and proper nutrition, and genetics contribute to solving the problems of plant protection.

– Rustam Rashitovich, please tell us about the problems (diseases, pests, etc.) that are effectively solved with the help of biology, using examples? When biologics work as a ready-made solution to a problem along the link: “problem – drug”.

— The bioinsecticide BioSleep BW, when applied to industrial crops, will be effective in the fight against lepidopterous insect pests (cotton scoop, cabbage moth, meadow moth, and others). If we take greenhouse farms, then this biopesticide will work highly effectively in the fight against whitefly, aphids, thrips. In orchards, vineyards, harmful objects against which BioSleep BW can be worked out are spider mites, leafworms, and codling moth.

Our range of fungicides (Pseudobacterin-3, Orgamica S, Orgamica F) effectively address plant disease problems.

Septoria on cereals, blast on rice (which is very important for the Kuban, where almost a million tons of rice is harvested annually), cercosporosis and bacterial spot on sugar beets, snow mold and powdery mildew on field crops, seed infection on cereals. We had a positive experience with bacterial burn, scab that affected gardens last year in Kyrgyzstan. Also, in the amount of 3000 liters, a drug was purchased for carrying out treatments by one of the farms of this republic in 2022.

Our fungicides are effective in combating vascular bacteriosis, tracheomycosis wilt on vegetables when grown in a drip irrigation system.

If farmers need to protect their plants from herbicide stress, Biodux growth regulator is in their arsenal.

– In general, biological products are used for three purposes: preventive, diagnostic and therapeutic (+growth stimulating). Which direction do you think is the future and why?

“Biology itself works differently than chemistry does. These are living organisms that in any case – with us or without us – are present in the soil and in all environments where plants develop. On plants, in the root system, in soil, in water.

Chemical preparations during their work prophylactically suppress all beneficial and non-useful microorganisms or work according to symptoms. With biology it may be so, or it may be somewhat different.

In general, we have adopted the philosophy of ecosystem formation for ourselves. An ecosystem that is present in the field, in the soil, on the seeds in any case. It can be risky – that is, carry pathogens, and pathogens can be in high prevalence. Or maybe suppressive. Our task as biologists is to form this ecosystem in all planes, in all habitats of the plant, which will be suppressive, that is, to exclude pathogens as much as possible. And not only at the micro level, but also at the macro level. This applies to both disease and pest control. It is possible to initially minimize the population of harmful objects in the soil due to the predominance of beneficial entomopathogenic microorganisms, both on the surface of the leaf, and inside the plant, and in the soil. Therefore, biology can be applied in all three areas of protection.

Of course, prevention is always more effective, because the agrarian does not start the problem, does not receive the triggering of risks. On the other hand, the desire to save money often pushes the manufacturer to start working against harmful objects already when the problem has become very acute and has been identified by him. In this case, the effectiveness already depends on the level of monitoring that is carried out on your farm. How tightly and constantly you lead it, keep track of everything that happens on the field. In order not to start the problem and have time to work on time with biological products or chemistry.

As a rule, large agricultural holdings work proactively. This is the most efficient way for them. Small farmers try to save money and have the possibility of personal control, they can come to their fields every day – in the case when, for example, their areas are small. Therefore, such a choice is reasonable for them: he diagnoses the fields himself, uses drugs when he fixes the problem.

— Can farmers fully protect their crops with integrated biosecurity?

– A farmer can choose an effective defense strategy for himself, it can be the one that, in his opinion, is optimal. If there is a preference to work with chemicals, because there is experience in this, then he can solve problems with the help of this direction. If he understands that for him chemical protection carries some risks – in terms of cost, the emergence of resistance, inefficiency, then, of course, today the level of development of the bioindustry allows him to work out the technology of integrated protection or fully biologized – in the case of organic farming. In both cases, this will reduce the chemical load or eliminate it altogether. Get away from chemicals in the issue of fungicidal and insecticidal protection. To increase the efficiency of nutrition, stimulation, protection against climatic stresses of plants. There is no need to bring to emergency situations on the field – now there is a whole range of drugs necessary for this. “Bionovatik” offers comprehensive programs where we have balanced entire packages of solutions that cover the entire range of problems in a wide range of temperatures and humidity. And we have adapted these packages for each field crop. The farmer receives a balanced package of products with a wide spectrum of action at the best price.

– Can biologics completely replace HSZR over time?

“It’s not a task to simply change something for something. The technology company “Bionovatik” does not put these goals at the forefront, but tries to find the optimal solution. Find the best effective solution in the current moment. Today it might be a chemical because it’s more developed, more tested, cheaper, tomorrow it might be a biological product, or a genetically modified strain, or just a combination of the two. Therefore, we also work with manufacturers of top chemical preparations – global and Russian – in the format of integration. And we do not compete – we have one common task. Each of us brings some efficiency to the farmer. And together we can sometimes give a better solution than alone.

— Are there solutions that can replace herbicides?

“Certainly, it is possible to find a solution that can replace chemical herbicides. These can be mechanical, optical solutions, precision farming, precision spraying. But then again, why change? Only to find a better solution. And less harmful to the environment, causing less damage. Biology can replace certain types of chemical herbicides. Perhaps even all. But this is a great scientific work. And the company “Bionovatik” has moved in this direction.