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Arthritis: What can prevent stomach ulcers caused by painkillers and who needs such protection?

 

Regular use of non-steroidal anti-inflammatory drugs (NSAIDs) such as diclofenac or ibuprofen can cause ulcers in the stomach and intestine. But the risk can be significantly reduced by taking particular medications.

Many people who have osteo- or rheumatoid arthritis take non-steroidal anti-inflammatory drugs (NSAIDs) to relieve pain and swelling in their joints. Commonly used NSAIDs include ibuprofendiclofenac and naproxen, for example. One disadvantage of these drugs is that they often causestomach ulcers when taken over several weeks or months. Sometimes ulcers develop in the duodenum too. The duodenum is the first part of the small intestine or gut, connecting the stomach to the rest of the small intestine. You can read more about how the stomach and intestine work in ourfeature "Digestive system".

The reason ulcers develop is because NSAIDs inhibit the production of hormones called prostaglandins. Prostaglandins stimulate the secretion of mucus and substances that neutralize acid in the stomach. The lack of prostaglandins means that the lining of the stomach is no longer properly protected from the acid, making it easier for a stomach ulcer to develop.

The main symptom of stomach ulcers – also called gastric ulcers – is a pressing pain in the upper abdomen. The pain is particularly noticeable just after eating, when the stomach produces more acid, but it can also arise independently of meals. Stomach ulcers that come from using painkillers might not cause any pain at all. Sometimes people only find out that they have an ulcer if they have serious complications such as bleeding in the stomach or a hole in the stomach wall (perforation).

For people who take NSAIDs over one year, the risk of having serious complications like this is between 1 and 2% on average. In other words, out of every hundred people who take this medication regularly over a period of one year, one or two experience serious side effects. Black stools are a typical sign of bleedingin the stomach or duodenum. The blood in the stool is black because it has already been broken down by stomach acid.

Various medications can be used to reduce the chances of an ulcer forming in the stomach or duodenum. These include drugs that inhibit the production of stomach acid, such as H2 blockers (also known as H2 receptor antagonists) and proton pump inhibitors. Cimetidinefamotidine and ranitidine are examples of H2 blockers. Omeprazole and pantoprazole are the most commonly used proton pump inhibitors in Germany.

Sometimes a drug called misoprostol is used too. Misoprostol is a hormone-like substance, which, among other things, aims to stimulate the secretion of protective mucus in the stomach. In Germany, misoprostol is marketed as a combination product with the NSAID diclofenac.

Some people are more prone to stomach and intestinal ulcers than others

Not all people who take NSAIDs also need to take medication to protect them from ulcers in the stomach and intestine. Whether or not a person might benefit from a drug like this will mainly depend on their personal risk factors for developing this kind of ulcer. The risk is greater if someone is over 65 years old or has had this kind of ulcer in the past. People who take antidepressant medication from a group of drugs called selective serotonin reuptake inhibitors (SSRIs) or steroids at the same time are also at greater risk of developing an ulcer. This is also the case for people who take several NSAIDs at the same time: particularly people who have already had a heart attack or a stroke often already take the NSAID acetylsalicylic acid (ASA, or ASS in German) to lower the risk of complications.

Ulcers are less likely in younger people who do not have risk factors. This means that they hardly benefit from medications that aim to prevent ulcers in the stomach and intestine. So it is important to take personal risk factors into account when deciding whether or not it would make sense for someone to use this kind of medication.

Research on the prevention of ulcers in the stomach and intestine

A group of researchers from the Cochrane Collaboration looked for trials in which NSAIDs were used in combination with an H2 blocker, a proton pump inhibitor or misoprostol to prevent or treat ulcers in the stomach and intestine. The Cochrane Collaboration is an international network of researchers who assess the benefits and harms of health care interventions. The researchers found 41 trials involving more than 21,000 participants. This provided enough data to assess the drugs.

Most of the people in the trials were men and women who had osteoarthritis or inflammatory conditions, including rheumatoid arthritis. All of them took one or more NSAIDs over a period of at least three weeks and had a fairly high risk of developing a stomach or intestinal ulcer. For each of the three groups of drugs, the researchers found several trials in which they were compared with a placebo (dummy drug) or with one another. The participants were monitored for up to a year. An endoscopy test was performed in nearly all of the trials to see whether any ulcers had formed in the stomach or duodenum, regardless of whether the participants had any typical symptoms or not. This means that the researchers also included symptomless ulcers in their assessment.

Proton pump inhibitors lower the risk of ulcers in the stomach and intestine

The proton pump inhibitors used in the trials were lansoprazoleomeprazole and pantoprazole. The trials lasted up to six months. All of the drugs in this group were found to clearly reduce the risk of ulcers in the stomach and intestine when compared to a placebo:

  • Out of every 100 people who took medication to protect the lining of their stomach, 14 developed an ulcer in their stomach or intestine.
  • Out of every 100 people who only took a placebo, however, 36 developed an ulcer.

In other words: 22 out of 100 people benefited from taking proton pump inhibitors – they would have developed an NSAID-induced ulcer otherwise.

The trials also looked at how common it was for people to stop taking medication to protect their stomach lining because of adverse effects. Compared to people who were taking a placebo, it was not more common for people taking proton pump inhibitors to stop taking their medication due to adverse effects. This suggests that proton pump inhibitors are relatively well tolerated. There were not enough participants in the available trials to be sure whether these medications are safe in the long term, however.

In May 2010, the U.S. regulatory authority Food and Drug Administration (FDA) determined that a note had to be included in the U.S. package inserts of proton pump inhibitors stating that long-term use might increase the risk of bone fractures. People over the age of 50 years who had to take proton pump inhibitors at a high dose or over a longer period of time (one year) had been found to have more fractures of the hip, the spine or the wrist.

The drug doses used in the trials were 15 or 30 mg of lansoprazole per day, 20 mg of omeprazole per day and 40 mg of pantoprazole per day.

H2 blockers provide protection against ulcers when taken at higher doses

Most of the trials of H2 blockers tested the drugs famotidine and ranitidine. The trials lasted up to one year. Both of these drugs were found to prevent stomach and duodenal ulcers, but the dose made a major difference: at lower doses, the drugs only reduced the risk of developing ulcers in the duodenum, but stomach ulcers were about as common as in the placebo group. At higher doses, H2 blockers prevented both stomach and intestinal ulcers:

  • Out of every 100 people who took one of these drugs, 15 developed an ulcer in their stomach or intestine.
  • Out of every 100 people who took a placebo, however, 36 developed an ulcer.

In other words, 21 out of 100 people benefited from taking this medication – they would have developed a stomach ulcer otherwise. The doses that were found to be effective in the trials were 40 mg of famotidine twice a day and 300 mg of ranitidine twice a day. These drugs were also well tolerated.

Misoprostol is effective, but often causes stomach cramps and diarrhea

The researchers also found a lot of trials of misoprostol. These showed that this drug, too, can prevent ulcers from developing in the stomach and intestine. But misoprostol has the disadvantage of often leading to adverse effects, particularly diarrhea and stomach cramps. Because of this, compared to people who were taking proton pump inhibitors, more people who were taking misoprostol stopped taking their medication. The diclofenac/misoprostol combination available in Germany was hardly tested in trials – so the advantages and disadvantages of this product in comparison with other treatments are unclear.

Making a decision and considering alternatives

All three groups of drugs can lower the risk of ulcers in the stomach and intestine. How effective they are and how many serious complications like bleeding they prevent is unclear: even bigger trials are needed to answer this question. Proton pump inhibitors and H2 blockers seem to be well tolerated. When using H2 blockers, however, it is important to make sure that the dose is high enough – this means that they usually need to be taken twice a day. H2 blockers can lose effectiveness over time because the body gets used to them. This problem does not seem to happen with proton pump inhibitors.

You can lower your risk of bleeding in the stomach by taking as low a dose of NSAIDs as possible and only taking them as long as necessary. You can read more about the side effects and how to avoid them in the feature “Adverse effects”.

Also, not everyone who has osteoarthritis needs to take NSAIDs. Acetaminophen (paracetamol) , for example, can be an alternative that does not increase the risk of stomach ulcers and might also reduce the pain enough. The advised dosages of acetaminophen need to be followed because this painkiller has side effects too: acetaminophen can put strain on the liver, for example, if the intervals in-between taking it are too short and the dosage is too high.

The personal risk of developing ulcers in the stomach and intestine varies from person to person. So not everyone who takes NSAIDs also needs to take medication to protect their stomach. You can talk to your doctor about whether or not you are at risk of developing stomach and intestinal ulcers, and which medications might be appropriate for you.

You can read more about muscles, bones and joints in our corresponding topic area.

Author: Institute for Quality and Efficiency in Health Care (IQWiG)

References

- IQWiG health information is based on research in the international literature. We identify the most scientifically reliable knowledge currently available, particularly what are known as “systematic reviews”. These summarize and analyze the results of scientific research on the benefits and harms of treatments and other health care interventions. This helps medical professionals and people who are affected by the medical condition to weigh up the pros and cons. You can read more about systematic reviews and why these can provide the most trustworthy evidence about the state of knowledge in the category “Evidence-based medicine”. The authors of the major systematic reviews on which our information is based are always approached to help us ensure the medical and scientific accuracy of our products.

- Rostom A, Dube C, Wells GA, Tugwell P et al. Prevention of NSAID-induced gastroduodenal ulcers. Cochrane Database of Systematic Reviews 2010, Issue 1. [Cochrane summary]