What can be expected from biologic drugs?
People with rheumatoid arthritis typically have permanent inflammations in several joints. This can cause pain, swelling, a lack of energy, joint stiffness and limited joint function. The small joints in the hands, fingers and feet are often affected first. But the bigger joints, such as the joints in the knees, hips and shoulders, can become inflamed too. The inflammations often lead to overall physical weakness. This can make people feel generally unwell, tired or exhausted.
Various treatments can help relieve the symptoms of rheumatoid arthritis. Disease-modifying medication can also delay, or sometimes even stop, the progression of the disease, thereby preventing permanent damage to the joints. The medical term for this kind of medication is “disease-modifying anti-rheumatic drugs” or DMARDs for short.
Using disease-modifying drugs
There are a number of disease-modifying drugs, differing in their effect, their potential side effects and how they are used. They can be divided up into “conventional” disease-modifying drugs and genetically engineered disease-modifying drugs, also known as “biologics.” Biologics are considered as a treatment for rheumatoid arthritis that has not improved enough with conventional disease-modifying drugs.
The following are the most commonly prescribed conventional disease-modifying drugs in Germany:
- Methotrexate (MTX)
The following biologics have been approved for use in Germany and other countries:
- Certolizumab pegol
Research on biologics
Researchers at the Institute for Quality and Efficiency in Health Care (IQWiG, Germany) looked into what people who have rheumatoid arthritis can expect from biologics when used as a second-line treatment. In other words, when biologics are used in people who have already tried out at least one conventional disease-modifying anti-rheumatic drug, but the treatment did not work. The researchers analyzed the results of 35 studies involving a total of about 13,000 participants. They only included studies that used biologics in the same way as they're officially meant to be used in Germany.
In most of the studies the biologics were used in combination with methotrexate. In nearly all of the studies the people in the comparison group used methotrexate and a fake medication (a placebo). Only one study directly compared two biologics – adalimumab and tocilizumab – with each other.
The effectiveness of the medication was assessed based on various criteria:
- Arthritis remission: Remission is when someone no longer has any arthritis symptoms or related problems, or only very few. This is determined based on how many swollen and painful joints they have, as well as how healthy they feel overall.
- Arthritis symptoms: These particularly include pain, morning stiffness and exhaustion (fatigue).
- Changes to the joints: Joint deformities and joint stiffness
- Overall physical function, including activities of daily living
- Ability to work and participate in social activities
- Health-related quality of life
- Life expectancy
- Side effects, especially infections
Five drugs shown to have clear benefit
Five drugs were found to reduce joint pain and swelling, lead to a remission and improve physical function when taken in addition to methotrexate: abatacept, adalimumab, certolizumab pegol, golimumab and tocilizumab.
The following example (adalimumab) might make it clearer what exactly people can expect from these medications:
- When receiving treatment with methotrexate alone, about 7 out of 100 people experienced a clear improvement in symptoms, or were symptom-free, within one year.
- When receiving treatment with a combination of methotrexate and adalimumab, about 23 out of 100 people experienced a clear improvement in symptoms, or were symptom-free, within one year.
In other words, about 16 out of 100 people benefited from using adalimumab in addition to basic therapy with methotrexate.
The outcome was similar for abatacept, certolizumab pegol, golimumab and tocilizumab. Other findings included the following:
- Abatacept and adalimumab reduced morning stiffness.
- Adalimumab and tocilizumab reduced fatigue.
- Abatacept, adalimumab and tocilizumab led to an improvement in quality of life.
- Adalimumab, certolizumab pegol, golimumab and tocilizumab reduced the general pain associated with arthritis.
- People who were treated with abatacept, adalimumab, certolizumab pegol or tocilizumab said the disease was less severe.
But the studies did not produce data on all of the medications and all of the criteria. For example, they hardly looked into how the drugs affected people’s quality of sleep or their overall health. The studies didn't include any information on changes in the joints.
Side effects of biologics
Biologics can have various side effects. The main side effect is an increased risk of infection: People are more likely to develop infections because biologics suppress their immune system. These side effects are proven for adalimumab, certolizumab pegol and tocilizumab, or the studies at least suggested that they led to more side effects.
Depending on how severe they are, infections are classified as non-serious or serious infections. An infection is considered to be serious if it is life-threatening, if it needs to be treated in a hospital, or if it has lasting effects – such as a serious lung infection.
Infections were quite common in the studies – regardless of whether people only used methotrexate or used a biologic drug too. For instance, the studies on adalimumab found the following:
- About 45 out of 100 people who were treated with methotrexate had an infection.
- About 54 out of 100 people who were treated with a combination of methotrexate and adalimumab had an infection.
Serious infections were much less common: About 1 out of 100 people who were treated with methotrexate alone had a serious infection, compared to about 3 out of 100 people who were treated with methotrexate and adalimumab.
Participants who took only methotrexate stopped treatment early in 3 out of 100 cases. This happened in about 8 out of 100 participants who took tocilizumab and methotrexate.
When looking at the frequency of side effects, the researchers didn't find any clear differences between the other medications that were included in the studies.
Comparing different biologics
Only one study directly compared two biologics – adalimumab and tocilizumab – with each other. The people in this study weren't able to use methotrexate because they didn't tolerate it well or because it hadn't worked when they tried it out. The study suggested that tocilizumab is more likely to lead to a remission than adalimumab in this group of people. As far as other treatment outcomes are concerned, it's not possible to draw any conclusions about which of the two medications is better or worse.
Due to a lack of research, it's not clear whether there are differences between the other biologics.
Institute for Quality and Efficiency in Health Care (IQWiG, Germany). Biotechnologically produced drugs as second-line therapy for rheumatoid arthritis: Executive summary; Commission A10-01. June 28, 2013. (IQWiG reports; Volume 180).
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