OBJECTIVES: To summarise, by a systematic literature review (SLR), the evidence regarding pharmacological and non-pharmacological therapeutic strategies in difficult-to-treat rheumatoid arthritis (D2T RA), informing the EULAR recommendations for the management of D2T RA.
METHODS: PubMed, Embase and Cochrane databases were searched up to December 2019. Relevant papers were selected and appraised.
RESULTS: Two hundred seven (207) papers studied therapeutic strategies. Limited evidence was found on effective and safe disease-modifying antirheumatic drugs (DMARDs) in patients with comorbidities and other contraindications that limit DMARD options (patients with obesity, hepatitis B and C, risk of venous thromboembolisms, pregnancy and lactation). In patients who previously failed biological (b-)DMARDs, all currently used b/targeted synthetic (ts-)DMARDs were found to be more effective than placebo. In patients who previously failed a tumour necrosis factor inhibitor (TNFi), there was a tendency of non-TNFi bDMARDs to be more effective than TNFis. Generally, effectiveness decreased in patients who previously failed a higher number of bDMARDs. Additionally, exercise, psychological, educational and self-management interventions were found to improve non-inflammatory complaints (mainly functional disability, pain, fatigue), education to improve goal setting, and self-management programmes, educational and psychological interventions to improve self-management.The identified evidence had several limitations: (1) no studies were found in patients with D2T RA specifically, (2) heterogeneous outcome criteria were used and (3) most studies had a moderate or high risk of bias.
CONCLUSIONS: This SLR underscores the scarcity of high-quality evidence on the pharmacological and non-pharmacological treatment of patients with D2T RA. Effectiveness of b/tsDMARDs decreased in RA patients who had failed a higher number of bDMARDs and a subsequent b/tsDMARD of a previously not targeted mechanism of action was somewhat more effective. Additionally, a beneficial effect of non-pharmacological interventions was found for improvement of non-inflammatory complaints, goal setting and self-management.
Objective: To evaluate the effectiveness of exercise and physical activity (PA) promotion on cardiovascular fitness, muscle strength, flexibility, neuromotor performance (eg, balance) and daily PA in people with rheumatoid arthritis (RA), spondyloarthritis (SpA) and hip/knee osteoarthritis (HOA/KOA). Methods: systematic review (SR) and meta-analysis (MA) were performed searching the databases PubMed/Medline, CENTRAL, Embase, Web of Science, Emcare and PsycInfo until April 2017. We included randomised controlled trials (RCTs) in adults (≥18 years) with RA, SpA and HOA/KOA, investigating the effects of exercise or PA promotion according to the public health PA recommendations by the American College of Sports Medicine. The time point of interest was the first assessment after the intervention period. If suitable, data were pooled in a MA using a random-effects model presented as standardised mean difference (SMD). Results: The SR included 63 RCTs, of which 49 (3909 people with RA/SpA/HOA/KOA) were included in the MA. Moderate effects were found of aerobic exercises and resistance training on cardiovascular fitness (SMD 0.56 (95% CI 0.38 to 0.75)) and muscle strength (SMD 0.54 (95% CI 0.35 to 0.72)), respectively, but no effect of combined strength/aerobic/flexibility exercises on flexibility (SMD 0.12 (95% CI -0.16 to 0.41)). PA promotion interventions produced a small increase in PA behaviour (SMD 0.21 (95% CI 0.03 to 0.38)). Conclusion: Exercises and PA promotion according to public health recommendations for PA improved cardiovascular fitness, muscle strength and PA behaviour, with moderate effect sizes in people with SpA, RA and HOA/KOA.
To summarise, by a systematic literature review (SLR), the evidence regarding pharmacological and non-pharmacological therapeutic strategies in difficult-to-treat rheumatoid arthritis (D2T RA), informing the EULAR recommendations for the management of D2T RA.
METHODS:
PubMed, Embase and Cochrane databases were searched up to December 2019. Relevant papers were selected and appraised.
RESULTS:
Two hundred seven (207) papers studied therapeutic strategies. Limited evidence was found on effective and safe disease-modifying antirheumatic drugs (DMARDs) in patients with comorbidities and other contraindications that limit DMARD options (patients with obesity, hepatitis B and C, risk of venous thromboembolisms, pregnancy and lactation). In patients who previously failed biological (b-)DMARDs, all currently used b/targeted synthetic (ts-)DMARDs were found to be more effective than placebo. In patients who previously failed a tumour necrosis factor inhibitor (TNFi), there was a tendency of non-TNFi bDMARDs to be more effective than TNFis. Generally, effectiveness decreased in patients who previously failed a higher number of bDMARDs. Additionally, exercise, psychological, educational and self-management interventions were found to improve non-inflammatory complaints (mainly functional disability, pain, fatigue), education to improve goal setting, and self-management programmes, educational and psychological interventions to improve self-management.The identified evidence had several limitations: (1) no studies were found in patients with D2T RA specifically, (2) heterogeneous outcome criteria were used and (3) most studies had a moderate or high risk of bias.
CONCLUSIONS:
This SLR underscores the scarcity of high-quality evidence on the pharmacological and non-pharmacological treatment of patients with D2T RA. Effectiveness of b/tsDMARDs decreased in RA patients who had failed a higher number of bDMARDs and a subsequent b/tsDMARD of a previously not targeted mechanism of action was somewhat more effective. Additionally, a beneficial effect of non-pharmacological interventions was found for improvement of non-inflammatory complaints, goal setting and self-management.
