|Recommendation 1. In patients with active axSpA, we strongly recommend treatment with NSAIDs over no treatment, because they are effective for mitigating disease activity measures and improving functional status.||low||9.8|
|Recommendation 2. In patients with persistent active axSpA, we strongly recommend long-term over short-term use of NSAIDs, because they exhibit sustained symptomatic efficacy. We conditionally recommend that disease activity and adverse events should be regularly monitored, evaluating long-term risks versus benefits.||low||9.3|
|Recommendation 3. In patients with active axSpA, we conditionally recommend treatment with NSAIDs over no treatment for alleviate symptoms of peripheral arthritis and enthesitis, since few data have shown moderate efficacy in these clinical manifestations.||very low||8.8|
|2. WINDOW OF OPPORTUNITY AND TREATMENT STRATEGY|
|Recommendation 4. In patients with active axSpA, we strongly recommend NSAIDs as the first-line treatment over an immunobiologic agent, considering its low cost and satisfactory efficacy. The benefit of starting an immunobiologic agent in NSAIDs-naïve patients, even in those with poor prognostic criteria, is not proven.||low||8.6|
|Recommendation 5. In patients with active axSpA, we strongly recommend to immediately start a NSAID after the diagnosis because early treatment may increase the response rate.||very low||8.8|
|Recommendation 6. In patients with active axSpA, we strongly recommend to initiate NSAIDs at full dosage over low dosage, because they exhibit a tendency for greater efficacy in achieving ASAS 20, reduction of morning stiffness, BASDAI, pain, patient global assessment of disease activity, and BASFI. We conditionally recommend that the full dosages of NSAIDs should be maintained, with adequate monitoring, until good disease control is achieved.||low||9.4|
|Recommendation 7. In patients with active axSpA, in the absence of a response to the first NSAID at 4 weeks, we conditionally recommend switching to a second traditional NSAID or iCOX2. If the therapeutic target is not reached with the use of NSAIDs for 12 weeks, we strongly recommend to start an immunobiologic agent.||low to high||8.6|
|3. CONTINUOUS OR ON-DEMAND USE|
|Recommendation 8. In patients with active axSpA, we conditionally recommend to start continuous over on-demand NSAIDs until symptoms relief is achieved. After clinical improvement or the clinical target (low disease activity or remission) has been achieved, the full dosage can be reduced or switched to on-demand strategy. Before prescribing continuous NSAIDs, it is important to take into account: the patient’s opinion, comorbidities and risk factors.||very low to moderate||9.4|
|4. RADIOGRAPHIC PROGRESSION|
|Recommendation 9. Regarding radiographic progression, in patients with active axSpA, we conditionally recommend continuous over on demand use of NSAIDs. Considering controversial results among the studies, we conditionally recommend switching to on demand strategy in inactive disease. We conditionally recommend against switching NSAIDs to immunobiological therapy when there is radiographic progression without evidence of disease activity, because the risk/benefit ratio of starting an immunobiologic agent in this scenario is not clear.||Very low||8.2|
|5. COMPARISON AMONG NSAIDs|
|Recommendation 10. In patients with active axSpA, we conditionally recommend that the choice of specific NSAID should be based on patient’s profile (age, prior toxicity, comorbidities) and on shared decision making. To date, there is no consistent evidence of efficacy and safety differences among the NSAIDs (non-selective or iCOX2) in axSpA.||low||9.6|
|6. SAFETY AND ADVERSE REACTIONS|
Recommendation 11. Regarding safety, in patients with active axSpA, we strongly recommend treatment with NSAIDs over no treatment, because the available evidence showed an overall good safety profile of these drugs in axSpA.|
We conditionally recommend that NSAIDS should be used with caution in individuals with risk factors (age > 65 years, diabetes mellitus, use of aspirin, corticosteroids and other platelet antiaggregants, renal or liver diseases). The risks and benefits of starting them should be shared and individualized according to the patient’s risk profile.
Recommendation 12. In patients with active axSpA, we conditionally recommend to avoid NSAIDs (non-selective or iCOX2) and to start an immunobiologic agent in those with current or previous peptic ulcer or gastrointestinal bleeding.|
We conditionally recommend the use of an iCOX2 agent over a traditional NSAID in patients with gastrointestinal risk factors.
We strongly recommend the use of concomitant gastroprotective drugs in symptomatic or high-risk patients.
|Recommendation 13. In patients with active axSpA, we conditionally recommend to avoid NSAID therapy and to start an immunobiologic agent in those with cardiovascular risk factors, mainly in those with previous acute myocardial infarction or stroke, especially if recent (past 12 months).||very low (observational studies)||8.4|
Recommendation 14. In patients with active axSpA, we conditionally recommend to avoid NSAIDs and to start an immunobiologic agent in thoses with increased risk of renal adverse events. The decision should be individualized and risk/benefits shared with the patient.|
We strongly recommend caution and regular monitoring of renal function, especially in high-risk individuals (elderly, hypertension, diabetes, kidney dysfunction).
|very low (observa-tional studies)||9.4|