Indomethacin, etoricoxib and prednisolone were found to be equally effective in the treatment of gouty arthritis. However, prednisolone showed fewer AEs and was better than the other two in reducing joint inflammation.

Acute gouty arthritis (AGA), with the global incidence of around 0.03% in women and 0.08% or 0.13% in men, is one of the most common inflammatory joint diseases. It is more prevalent in men above 40 years of age. It occurs due to the deposition of monosodium urate crystals, linked to purine metabolic disorder. AGA consists of three stages. It starts with increased uric acid levels (hyperuricemia), but there are no symptoms. The second stage is when recurrent gout attacks occur with no symptoms. The third stage of gout is long-term chronic gout with no symptom-relief. Patients suffering from gout may usually come up with pain as their primary symptom, but the treatment strategy should consider inflammation control along with pain. The underlying mechanism resulting in an inflammatory response is not entirely known. Previous studies have suggested the involvement of environmental toxin 4-Nonylphenol in promoting inflammatory response in IBD. However, it is not known if this toxin plays a role in the inflammatory response of AGA.

NSAIDs are currently the choice of treatment for AGA due to their significant property of relieving pain and inhibiting inflammation. Indomethacin 50 mg three times a day is considered a standard treatment for AGA. However, many studies have indicated that there are many adverse events (AEs) linked to indomethacin use. NSAIDs with less AEs, i.e. selective COX-2 inhibitors, were formulated. These agents work by inhibiting the COX-2 enzyme responsible for catalyzing the prostaglandin synthesis. Unlike other NSAIDs, selective COX-2 inhibitors produce less gastrointestinal AEs but offer similar analgesic and anti-inflammatory properties. Etoricoxib, a selective COX-2 inhibitor, is widely used for treating gout. Research has even suggested corticosteroids to be an effective and safe alternative for treating gout in older adults. A study result indicated that prednisolone 35 mg once a day for five days was safe and offered equivalent efficacy to naproxen 500 mg twice a day for gout management. 

Rationale behind research: Many clinical studies have compared the effectiveness of prednisolone or etoricoxib with indomethacin. But, there is a lack of studies evaluating the comparative efficacy and safety of all three drugs i.e. indomethacin, prednisolone and etoricoxib in the treatment of AGA.

Objective: The present open-label randomized and active comparator trial was carried out to evaluate the comparative efficacy (analgesic and anti-inflammatory) and safety/tolerability of indomethacin 50 mg thrice a day etoricoxib 120 mg once a day and prednisolone 35 mg once a day for treating AGA

Study Outcomes:

Baseline: Patients’ demographic characteristics and pain intensity were assessed at the baseline.

Primary Outcomes: Reduction of pain in the index joint as experienced by the patient: assessed using 5-point Likert scale (0=very good, 1 =good, 2=fair, 3= poor, 4= very poor).

Secondary Outcomes:

Changes of physician’s assessment of following parameters from baseline:

• Tenderness: assessed using 3-point Likert scale (0=no pain, 1=patient states ‘there is pain’, 2=patient states, ‘there is pain’ and withdraws his affected limbs)
• Erythema: assessed using 3-point Likert scale (0=absent, 1=not assessable, 3=present)
• Swelling: assessed using 4-point Likert scale (0=no swelling, 1=palpable, 2=visible, 3=bulging beyond the joint margins)
• Joint activity: assessed using 4-point Likert scale (0=no restriction, 1=moderately restricted, 2=significantly restricted, not engaging in general activities, 3=unbearable, cannot take care of themselves)

Patients’ global assessment of response to therapy: assessed using 5-point Likert scale (0=very good, 1 =good, 2=fair, 3= poor, 4= very poor)

AEs: Gastric or abdominal pain, dizziness, edema, fatigue or drowsiness, and dry mouth were recorded

Time Points:

• Primary Outcomes: Baseline and 4 h after the first dose of drugs on days 2 to 4
• Secondary Outcomes: Baseline and at the end of the study on day 4

Outcomes:

Primary and Secondary outcomes: A significant reduction in symptoms of acute gout attack in time- patients' assessment of pain, physician assessment of joint swelling, tenderness, erythema and activity were noted with all the three drugs. The reduction of pain and tenderness was similar with oral prednisolone, etoricoxib, and indomethacin (Figure 1). Oral prednisolone, etoricoxib, and indomethacin were similar in the efficacy of reducing inflammation indicator i.e. erythema (Figure 1). But, indomethacin caused a more significant reduction in swelling as compared to indomethacin (Figure 1). The joint activity was equally improved with all the three drugs. (Figure 1)  Also, the patients' response to global therapy was similar for all the three drugs (Figure 2).

AEs: In indomethacin group, the total AEs observed were significantly more frequent as compared to the other two groups.

The current study was conducted to evaluate the comparative efficacy and safety of indomethacin, prednisolone and etoricoxib, for the treatment of AGA. The study outcomes demonstrated similar efficacy of indomethacin, oral prednisolone and etoricoxib in improving pain, tenderness, and joint activity in patients with AGA after four days.  All three drugs were equally effective in reducing inflammation. However, the swelling reduction was more pronounced with prednisolone compared to other drugs. In all the three groups, the patients' assessment of response was found to be similar.

As per 2012 ACR guidelines, the single use of systemic corticosteroids, oral colchicine and NSAIDs is recommended without prioritizing one over the other. The condition of the patient and the presence of comorbidities should be the criteria to decide the treatment. Colchicine was not used in the study as it quickly results in AEs due to its similar therapeutic and toxic doses. Two NSAIDs, etoricoxib and indomethacin, were used in the study which is recommended as first-line treatment for AGA.  Etorixicib showed comparable efficacy to that of indomethacin, suggesting that this selective COX-2 inhibitor is an effective treatment for AGA. 

Indomethacin, on the other side, showed a higher incidence of adverse events which suggest that etoricoxib could be a better choice over indomethacin for treating AGA. Prednisolone also showed similar efficacy to indomethacin. However, it was better than indomethacin in reducing joint swelling. Few studies have suggested the use of corticosteroids in early stages of disease for quick symptomatic relief, but its more use can be related to severe adverse effects. The use of corticosteroids in moderation may lead to fewer AEs. Also, there were fewer gastrointestinal tract related AEs observed with prednisolone than those with NSAIDs. Although all the three drugs had comparable efficacy, prednisolone was better than the other two in reducing joint swelling. It was also associated with fewer AEs compared to the other two.