Should CPPD (Calcium Pyrophosphate Deposition Disease) be treated with both colchicine and indomethacin?

From the Guidelines

The treatment of CPPD (Calcium Pyrophosphate Deposition Disease) typically does not require both colchicine and indomethacin simultaneously as first-line therapy. For acute CPPD flares, either medication can be effective when used individually.

Key Considerations

• Colchicine can be used at 0.5 mg up to 3–4 times a day with or without an initial dose of 1 mg for acute flares, as recommended by the EULAR guidelines 1.
• Indomethacin, typically dosed at 25-50 mg three times daily during acute episodes, is an alternative NSAID option.
• The choice between these medications should be based on the patient's comorbidities, medication tolerances, and risk factors.
• Colchicine works by inhibiting neutrophil function and inflammatory pathways, while indomethacin reduces inflammation through prostaglandin inhibition.
• In severe or refractory cases, combination therapy might be considered, but this approach increases the risk of side effects, particularly gastrointestinal issues.

Side Effects and Precautions

• Colchicine can cause diarrhea and should be used cautiously in patients with renal or hepatic impairment.
• Indomethacin may cause gastric irritation, fluid retention, and kidney problems.
• Treatment should always be individualized, with consideration of the lowest effective dose for the shortest necessary duration, as supported by the evidence on NSAID and colchicine use in CPPD management 1.

Evidence-Based Recommendations

• The EULAR guidelines recommend oral NSAID (with gastroprotective treatment if indicated) and low-dose oral colchicine as effective systemic treatments for acute CPP crystal arthritis, although their use is often limited by toxicity and comorbidity 1.
• The guidelines also suggest that prophylaxis against frequent recurrent acute CPP crystal arthritis can be achieved with low-dose oral colchicine or low-dose oral NSAID (with gastroprotective treatment if indicated) 1.

From the Research

Treatment Options for CPPD

• CPPD (Calcium Pyrophosphate Deposition Disease) is a common cause of acute and chronic arthritis, and its treatment is currently based on expert opinion and evidence derived from the treatment of gout 2.
• Commonly used treatments for CPPD include non-steroidal anti-inflammatory drugs (NSAIDs), colchicine, and corticosteroids, which are extrapolated from use in gout 3.
• There is limited evidence to support the use of specific treatment agents for CPPD, and high-quality evidence is needed to guide clinicians 2, 3.

Use of Colchicine and Indomethacin

• Colchicine is commonly used to treat CPPD, and it has been shown to be effective in reducing the frequency and severity of clinical symptoms 2, 3.
• Indomethacin is a type of NSAID that is often used to treat inflammatory conditions, including pericarditis 4, 5.
• However, there is limited evidence to support the use of indomethacin specifically for CPPD, and its use is not well established in the treatment of this condition 2, 3.

Combination Therapy

• Combination therapy with colchicine and NSAIDs (such as indomethacin) may be effective in preventing recurrences of acute idiopathic pericarditis 5.
• However, the evidence for this combination in CPPD is limited, and more research is needed to determine its efficacy and safety in this population 2, 3.
• Anakinra, a biologic agent, has been shown to be effective in refractory CPPD, and may be considered as an alternative treatment option 6.