Pain in patients with inflammatory arthritis and gastrointestinal or liver problems

This summary of a Cochrane review presents what we know from research about the effect of pain relieving drugs for people with inflammatory arthritis plus stomach or gut disease, or liver disease.

The review shows the following in people with inflammatory arthritis plus stomach or gut disease, such as hernia or stomach or intestinal ulcers or previous bleeding from the stomach or intestine, or patients with liver diseases such as hepatitis or fatty liver:

- We are uncertain if naproxen (Aleve®, Naprosyn®) produced more side effects in people with inflammatory arthiritis plus stomach or intestine disease, compared with people with inflammatory arthritis without stomach or intestine disease, because only a single study giving low quality evidence was available.

- No studies were found that looked at pain relief.

- No studies were found that looked at other pain-relieving drugs.

- No studies were found in people with conditions other than rheumatoid arthritis.

- No studies were found in people with inflammatory arthritis plus liver disease.

We do not have precise information about side effects and complications, particularly for rare but serious side effects. Possible side effects associated with high dose paracetamol include liver problems. Aspirin and NSAIDs may cause stomach, kidney or heart problems.

What is inflammatory arthritis and what is pain management

Inflammatory arthritis is a group of diseases that includes rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and other types of spondyloarthritis. When you have inflammatory arthritis your immune system, which normally fights infection, attacks your joints. This makes your joints swollen, stiff and painful. In rheumatoid arthritis, the small joints of your hands and feet are usually affected first. In contrast, in ankylosing spondylitis the joints of the spine are the most affected. There is no cure for inflammatory arthritis at present, so the treatments aim to relieve pain and stiffness and improve your ability to move.

Paracetamol, or acetaminophen, is used to relieve pain but does not affect swelling; non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, diclofenac, naproxen and COX-2s (for example celecoxib) are used to decrease pain and swelling. Opioids, such as codeine-containing Tylenol®, hydromorphone (Dilaudid®), oxycodone (Percocet®, Percodan®), morphine and the opioid-like drug tramadol are powerful pain-relieving substances. Other drugs have some pain-relieving properties and can therefore be used to control pain. This is the case of the so-called neuromodulators, such as antidepressants (for example fluoxetine, paroxetine, amitriptyline), anticonvulsants (for example gabapentine, pregabaline) or muscle relaxants (for example diazepam).

Authors' conclusions: 

On the basis of the current review, there is scant evidence to guide clinicians about how gastrointestinal or liver comorbidities should influence the choice of pain treatment in patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis or other spondyloarthritis. Based upon additional studies that included a mixed population of participants with a range of rheumatic conditions, NSAIDs should be used cautiously in patients with inflammatory arthritis and a history of gastrointestinaI comorbidity as there is consistent evidence that they may be at increased risk.

Read the full abstract...

Even with optimal disease-modifying treatment and good control of disease activity, persistent pain due to structural damage is common in people with inflammatory arthritis and therefore additional treatment for pain might be required. Because comorbidity is highly prevalent in people with inflammatory arthritis, it is important to consider comorbidities such as gastrointestinal or liver diseases in deciding upon optimal pharmacologic pain therapy.


To assess the efficacy and safety of pharmacological pain treatment in patients with inflammatory arthritis who have gastrointestinal or liver comorbidities, or both.

Search strategy: 

We searched Cochrane CENTRAL, MEDLINE and EMBASE for studies, to June 2010. We also searched the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) conference abstracts (2007 to 2010) and performed a handsearch of reference lists of articles.

Selection criteria: 

All randomised or quasi-randomised controlled trials (RCTs or CCTs) were considered for inclusion, for the assessment of efficacy. For safety, we also considered single arm trials, controlled before-after studies, interrupted time series, cohort and case-control studies, and case series of 10 or more consecutive cases. Pain therapy comprised paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), opioids, opioid-like drugs (tramadol) and neuromodulators (antidepressants, anticonvulsants and muscle relaxants). The study population comprised adults (≥ 18 years) with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis or other spondyloarthritis who had gastrointestinal or hepatic, or both, comorbid conditions. Outcomes of interest were pain, adverse effects, function and quality of life. Studies that included a mixed population of inflammatory arthritis and other conditions were included only if results for inflammatory arthritis were reported separately.

Data collection and analysis: 

Two review authors independently selected trials for inclusion, assessed risk of bias and extracted data.

Main results: 

From 2869 identified articles only one single arm open trial fulfilled our inclusion criteria. This trial assessed the safety and efficacy of naproxen (dosage not specified) in 58 patients with active rheumatoid arthritis and gastrointestinal comorbidities for up to 52 weeks. Thirteen participants (22%) remained on gold therapy, four participants (10%) remained on hydroxychloroquine, 27 (47%) remained on corticosteroids, 12 (21%) remained on salicylates and all participants continued on antacids and a bland diet. The presence of faecal occult blood was reported in 1/58 participants tested between weeks 1 to 26 and 2/32 participants tested between weeks 27 to 52. Over the course of the study, seven participants (12.1%) withdrew due to adverse events but, of these, only two participants withdrew due to gastrointestinal side effects (abdominal pain n = 1, nausea n = 1) and no serious adverse events were reported. It was noteable that out of 14 studies excluded due to inclusion of a mixed population (osteoarthritis or other rheumatic conditions) or an intervention that was already withdrawn, five trials reported a higher risk of developing gastrointestinal events in patients with prior gastrointestinal events when treated with NSAIDs.