Glucocorticoid treatments (also called corticosteroids or steroids) are important tools in the management of RA, primarily as adjunct (term that refers to a treatment that is used in a supportive role) to disease-modifying treatments, such as disease-modifying anti-rheumatic drugs (DMARDs), including newer biologic treatments.
Glucocorticoids: a “bridge” therapy
Glucocorticoids are strong anti-inflammatory drugs that can be used to provide rapid control of disease activity such as inflammation. Because there is increased risk for side effects with long-term use, glucocorticoids are generally used as a “bridge” therapy in patients with active disease who have started DMARD treatment, which can take from 4 to 6 weeks to achieve full effect. Steroids are particularly effective in providing rapid control of inflammation and associated symptoms during RA disease flares.
Once a DMARD has taken effect, steroids are typically tapered down (a gradual decrease in dose) and discontinued once control of disease activity and symptoms has been achieved. Steroid treatments must be tapered and should not be discontinued abruptly.
How do steroids work?
Glucocorticoids exert their potent anti-inflammatory and immunomodulatory (changing the way the immune system works in a specific way) effects by inhibiting key immune system cells and chemicals that play a role in inflammation. They achieve their effects by several different mechanisms, most importantly by interfering with how genes work to synthesize key immune system components.1 Glucocorticoids are also considered immunosuppressants.
How are glucocorticoids taken?
Glucocorticoids are available for oral administration, intramuscular injection, and IV infusion. Some common oral formulations used in RA include prednisone (Deltasone, Cordrol), prednisolone (Prelone), dexamethasone (Decadron), and methylprednisolone (Medrol). Some examples of steroids formulated for injection or IV infusion include methylprednisolone (Solu-Medrol) and dexamethasone (Dexasone). Steroids may also be injected directly into affected joints to reduce inflammation (synovitis). A long-acting steroid, such as triamcinolone hexacetonide (Aristocort or Aristopak), is often used for intra-articular steroid injections.
Because of the risk for side effects with long-term use, glucocorticoids are usually limited to short-term use. However, in some patients with severe RA, it may be necessary to continue treatment with glucocorticoids for long periods at low doses (less than 10 mg/day).
What evidence is there that glucocorticoids work?
The effectiveness of short-term use (1 month or less) of steroids to control disease activity has been demonstrated in a number of studies. One meta-analysis (an analysis that looks at results from a number of studies) of 10 randomized studies including 320 patients with RA found that low-dose prednisolone (15 mg or less per day) resulted in greater decreases in joint tenderness and pain than NSAIDs and placebo and a greater increase in grip strength than placebo.2 Short-term use of glucocorticoid treatment at a low dose equivalent to prednisolone 15 mg per day or less is associated with very low risk for serious side effects.1
Other studies have tested the benefit of short-term use of high-dose glucocorticoid treatment in early RA. Two studies (COBRA and BeST) found that prednisone started at 60 mg per day, tapered to 7.5 mg per day by week 6, and discontinued by week 12, when given with traditional DMARD treatment, inhibited the progression of joint damage. Furthermore, this beneficial effect was maintained over the course of several years.3,4
No studies to date have tested short-term intermediate doses (between low and high doses) of glucocorticoids in RA. Nor have glucocorticoids been compared directly with newer biologic DMARDs.1
Long-term use of glucocorticoids is controversial due to the increased risk for serious side effects (such as bone loss, mood changes [depression and anxiety], or aggravation of diabetes), as well as a decrease in effectiveness of symptom control over time.1
Results form studies testing low-dose glucocorticoid treatment (for example, prednisolone 7.5 mg per day) for up to 2 years found that there were initial benefits in terms of symptom reductions, some of which were sustained for 2 years. Additionally, progression of joint damage was reduced over the 2-year period. It is unclear whether similar benefits can be achieved with long-term treatment at lower doses. However, some patients may derive benefits from very low dose glucocorticoid treatment (prednisone 1-4 mg per day) continued indefinitely, taken along with DMARD therapy.1
What are the risks associated with chronic, long-term use of steroids?
The main risks associated with chronic use of steroid treatments (typically seen at doses of 10 mg per day or higher) include osteoporosis and increased risk of fractures, GI bleeding, diabetes, cataracts, infections, and effects on mood, energy, digestion, and immune system function. The risk of these side effects appears to increase with increased glucocorticoid dose.1
There are several precautions and warnings you should be aware of if you are receiving corticosteroid treatment.
Increased risk of infection
Glucocorticoids can increase your chances of getting an infection and make existing infections more difficult to treat. If you develop an infection while taking a steroid, you should tell your doctor immediately. While taking a steroid, you should avoid contact with anyone who has the chicken pox or measles.5
Heart and kidney problems
Glucocorticoids should be used with caution if you have heart or kidney problems, including congestive heart failure, hypertension, or kidney failure.5
Glucocorticoids can affect (i.e. increase) your blood sugar levels, which may be problematic, particularly if you have diabetes. If you notice changes in sugar tests (blood or urine), talk to your doctor.5
Pregnancy and nursing
Glucocorticoids should only be used in pregnant women if the benefits outweigh the risks. While there have been no adequate studies of glucocorticoids in pregnant women, animal studies have shown an increase in birth defects. Glucocorticoids do cross into the breast milk of women who are nursing and can have harmful effects on a nursing child. Therefore, you should talk to your doctor about whether you should nurse your child while receiving steroid treatment.5
Glucocorticoids can result in mood changes, ranging in intensity from mild to extreme. If you have a history of mood changes or mood disorders, (including depression, anxiety, and biopolar disorder, you should tell your doctor before you start steroid treatment and you should monitor any mood changes while you are receiving glucocorticoids.1
What is glucocorticoid pulse therapy?
Pulse therapy involves taking high doses of glucocorticoids over a short period of time. This approach is typically used to treat acute flares, as well as a “bridge” therapy until DMARD treatment reaches full effect. Typically, pulse therapy is given as a high-dose IV infusion, for instance IV methylprednisolone 1000 mg daily for 3 consecutive days once per month. Lower doses may also be used. Although, IV infusion is the preferred route of administration for pulse therapy, steroids may also be given orally or by intramuscular injection. Patients who receive steroid pulse therapy alone may have a response that lasts 6 to 8 weeks. If given in combination with DMARD treatment, responses can last much longer.1
How effective are intra-articular glucocorticoids?
Intra-articular injections (injections directly into affected joints) of glucocorticoids are commonly used in RA to control synovitis. This treatment approach can be very effective in controlling disease activity in individual joints. However, it is not disease-modifying and cannot slow or prevent joint damage. Typically, long-lasting steroids are used for intra-articular injection, such as triamcinolone hexacetonide.1
Serious adverse effects that occur rarely with intra-articular steroid injections include osteonecrosis (death of bone tissue), worsening of synovitis, and infection. To minimize risk for serious adverse effects, it is recommended that no more than four injections be given to an individual joint over the course of one year.1
Is periodic monitoring recommended for patients who receive glucocorticoids?
Monitoring requirements for glucocorticoid treatment will vary from patient to patient and depend on the duration of treatment and dose intensity. It is recommended that patients who receive glucocorticoid treatment be tested at baseline (before treatment has started) for1:
- Serum glucose
- Lipid profile
- Bone mineral density (BMD)
After treatment has been started, the following parameters should be checked during each visit1:
- Blood pressure
- Weight gain
- Visual changes
- Shortness of breath
- Polydipsia (excessive thirst)
Additionally, if chronic, long-term treatment with steroids is used, bone mineral density should be monitored at least yearly.1
Is there anything I can do to protect myself from bone loss related to steroid treatment?
If you are receiving chronic, long-term steroid treatment (for instance, prednisone 5 mg per day or more for over 6 months or 7.5 mg per day for over 3 months), you should also receive calcium supplementation (1,000 mg per day) and vitamin D (400-800 international units [IU] per day). If you experience bone loss, despite daily use of these supplements, treatment with a bisphosphonate (a drug that prevents loss of bone) should be considered.1