This summary of a Cochrane review presents what we know from research about the effect of a combination of two pain relieving drugs for pain control in inflammatory arthritis (IA).
We are uncertain if two pain relieving drugs such as paracetamol (also called acetaminophen) (e.g. Panadol® and Tylenol®) plus non-steroidal anti-inflammatory drugs (NSAIDs), or paracetamol plus aspirin compared with one drug improved pain, because only single studies of low quality evidence were available. For the same reason, we do not have precise information about side effects and complications.
What is IA, and what drugs are used to treat pain?
IA is a group of diseases that includes rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA) and other spondyloarthritis (SpA). When you have IA, your immune system, which normally fights infection, attacks your joints. This makes your joints swollen, stiff and painful. In RA, the small joints of your hands and feet are usually affected first. In contrast, in AS, the joints of the spine are the most affected. PsA is characterised by inflammation of the skin, psoriasis, and joints and, depending on the disease type, can affect the small joints of the hands and feet or more the spine. There is no cure for IA at present, so the treatments aim to relieve pain and stiffness and improve your ability to move. Patients are started on disease-modifying antirheumatic drugs (DMARDs) (e.g. methotrexate, sulphasalazine, hydroxychloroquine and leflunomide) as soon as possible in an attempt to control the inflammation and to prevent the progression of the disease. Many people continue to have pain despite optimal disease treatment and have the need for specific medication to control pain.
Several drugs can be used to treat pain in IA. Paracetamol/acetaminophen, is used to relieve pain but does not affect swelling; NSAIDs such as ibuprofen, diclofenac and COX-2s (e.g. celecoxib), are used to reduce pain and swelling; and opioids, such as codeine-containing Tylenol®, hydromorphone (Dilaudid), oxycodone (Percocet and Percodan), morphine and tramadol are powerful pain-relieving substances. Other drugs have some pain relieving properties and can therefore be used to mainly control pain. This is the case of the so-called neuromodulators, such as antidepressants (e.g. fluoxetine, paroxetine and amitriptyline), anticonvulsants (e.g. gabapentine and pregabaline) or muscle relaxants (e.g. diazepam). It is not clear if combining two of these drugs offers the best treatment and which drugs cause more side effects. It is known that, for instance, high doses of paracetamol/acetaminophen may cause stomach problems, such as ulcers, and NSAIDs may cause stomach, kidney or heart problems.
Best estimate of what happens to people with IA who take combination therapy for pain
There is insufficient evidence to establish the value of combination therapy over monotherapy for people with IA. We included 23 studies in this review, all at high risk of bias (i.e. high chance of giving invalid results). Twenty-two of the trials were in patients with RA and one in a mixed population (RA and osteoarthritis). There were no studies in patients with AS, PsA or SpA. Included studies were old (all but one were published before 1990) and patients were, in general, not on optimal disease-modifying antirheumatic drugs, as is standard current practice. Therefore, it is not possible to draw conclusions about the value of combination pain therapy over monotherapy for people with IA. Importantly, there are no studies addressing the value of combination therapy for patients with IA who have persistent pain despite optimal disease suppression. Well designed studies are needed to address this question.