Safety of non-steroidal anti-inflammatory drugs, including aspirin and paracetamol (acetaminophen) in people receiving methotrexate for inflammatory arthritis (rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, other spondyloarthritis)
ABSTRACT Methotrexate is routinely used in the treatment of inflammatory arthritis. There have been concerns regarding the safety of using concurrent non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, or paracetamol (acetaminophen), or both, in these people.
To systematically appraise and summarise the scientific evidence on the safety of using NSAIDs, including aspirin, or paracetamol, or both, with methotrexate in inflammatory arthritis; and to identify gaps in the current evidence, assess the implications of those gaps and to make recommendations for future research to address these deficiencies.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, second quarter 2010); MEDLINE (from 1950); EMBASE (from 1980); the Cochrane Database of Systematic Reviews (CDSR) and the Database of Abstracts of Reviews of Effects (DARE). We also handsearched the conference proceedings for the American College of Rheumatology (ACR) and European League against Rheumatism (EULAR) (2008 to 2009) and checked the websites of regulatory agencies for reported adverse events, labels and warnings.
Randomised controlled trials and non-randomised studies comparing the safety of methotrexate alone to methotrexate with concurrent NSAIDs, including aspirin, or paracetamol, or both, in people with inflammatory arthritis.
Two authors independently assessed the search results, extracted data and assessed the risk of bias of the included studies.
Seventeen publications out of 8681 identified studies were included in the review, all of which included people with rheumatoid arthritis using various NSAIDs, including aspirin. There were no identified studies for other forms of inflammatory arthritis.For NSAIDs, 13 studies were included that used concurrent NSAIDs, of which nine studies examined unspecified NSAIDs. The mean number of participants was 150.4 (range 19 to 315), mean duration 2182.9 (range 183 to 5490) days, although the study duration was not always clearly defined, and the studies were mainly of low to moderate quality. Two of these studies reported no evidence for increased risk of methotrexate-induced pulmonary disease; one study assessed the effect of concurrent NSAIDs on renal function and found no adverse effect; one study identified no adverse effect on liver function; three studies demonstrated no increase in methotrexate withdrawal; and one study showed no increase in all adverse events, including major toxic reactions. However, transient thrombocytopenia was demonstrated in one study, specifically when NSAIDs were taken on the same week day as methotrexate. This study was a retrospective review that involved small numbers only and was of moderate quality; these finding have not been replicated since.Four studies looked at specific NSAIDs (etodolac, piroxicam, celecoxib and etoricoxib), with a mean number of participants of 25.8 (range 14 to 50) and mean study duration of 16.8 (range 14 to 23) days. These studies were mainly of moderate quality. The studies were primarily pharmacokinetic studies but also reported adverse events as secondary outcomes. There were no clinically significant adverse effects with concomitant piroxicam or etodolac; and only mild adverse events with celecoxib or etoricoxib, such as nausea and vomiting, and headaches.For aspirin, seven studies provided data on adverse events with the use of aspirin and methotrexate. These studies included a mean number of participants of 100 (range 11 to 232), had a mean duration of 1325 (range 8 to 2928) days and were mainly of low to moderate quality. Two of the studies reported no evidence for increased risk of methotrexate-induced pulmonary disease and two studies showed no increase in all adverse events including major toxic reactions; however, none of these studies specified the dose of aspirin that was used. One study demonstrated that concurrent aspirin adversely affected liver function at a mean dose of 6.84 tablets of aspirin per day, which is a possible daily dose of 2.1 g presuming that 300 mg aspirin tablets were given. A further study described a partially reversible decline in renal function with 2 g daily of aspirin. One study reported no increase in adverse events with 975 g aspirin daily, however the study duration was only one week.For paracetamol, no studies were identified for inclusion.
In the management of rheumatoid arthritis, the concurrent use of NSAIDs with methotrexate appears to be safe provided appropriate monitoring is performed. The use of anti-inflammatory doses of aspirin should be avoided.
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ABSTRACT: This randomized, double-blind study was carried out to evaluate the effectiveness of etoricoxib in controlling the pain during lumbar fusion surgery of the degenerative lumbar scoliosis patients. We found that perioperative use of etoricoxib produced a significant reduction in the degree of pain compared to the patients treated with placebo. Etoricoxib eased the pain and helped to manage the discomfort of lumbar fusion surgery. In addition, etoricoxib was well tolerated as it caused no serious adverse reaction, suggesting a safe profile. Etoricoxib also appeared to ensure and promote the positive effect of surgery, however, insignificantly. Thus, the results suggest that etoricoxib was effective in safely managing the pain during the lumbar fusion surgery and recovery thereafter.Cell Biochemistry and Biophysics 11/2014; DOI:10.1007/s12013-014-0350-5 · 2.38 Impact Factor
Article: Methotrexate Induced Pancytopenia[Show abstract] [Hide abstract]
ABSTRACT: The well-reported methotrexate (MTX) toxicities are based on the duration and cumulative dosing of drug. The typical toxicities can be predicted by the timing of drug administration, where mucositis occurs as an earlier effect, while myelosuppression and the sequelae of pancytopenia occur later after MTX administration. Despite these well-known toxicities, low dose MTX therapy can become problematic, in particular with the elderly, who are at a greater risk for significant myelosuppression. We present a case of a 73-year-old female with pancytopenia causing severe neutropenia, mucocutaneous bleeding, and bruising and requiring intravenous antibiotic therapy and limited transfusion dependence as a result of low dose daily MTX for rheumatoid arthritis.05/2014; 2014:679580. DOI:10.1155/2014/679580
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ABSTRACT: Background Work participation of patients with inflammatory arthritis (IA) is important not only economically but also for physical and psychological health. There is no Cochrane Review to date on studies of non-pharmacological interventions specifically aimed at preventing job loss in people with IA. Objectives To assess the effects of non-pharmacological interventions that aim to prevent job loss, work absenteeism or improve work functioning for employees with IA (rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), other spondylarthritis (SpA) or IA associated with connective tissue diseases, such as Systemic Lupus Erythematosus (SLE)). Search methods We searched the following databases from inception up to 30 April 2014; The Cochrane Library (including Cochrane Central Register of Controlled Trials, i.e. CENTRAL and DARE), MEDLINE (PubMed), EMBASE (Embase.com), CINAHL (EbSCOhost), ClinicalTrials.gov and PsycINFO (ProQuest). We did not impose language restrictions in the search. Selection criteria We included randomised controlled trials (RCTs) that evaluated interventions aimed at preventing job loss in adults of working age (18 to 65 years) diagnosed with IA, including RA, AS, PsA, SpA or other types of IA. Primary outcomes were job loss and sickness absenteeism and the secondary outcome was work functioning. Data collection and analysis Two review authors independently selected trials for inclusion, extracted data and assessed risk of bias in the included RCTs. Main results We included three RCTs with a total of 414 participants at risk of job loss. The majority of participants had IA, most with RA and to a lesser degree AS. The interventions aimed to prevent job loss and improve work functioning in several ways: firstly by evaluating work changes or adaptations and secondly by providing any person-directed interventions including vocational counselling, advice or education. Interventions directly targeted at the work environment were minimal and included workplace visits (one trial) or any actions by an occupational physician (one trial). The duration or dose of the interventions varied from two 1.5-hour sessions (one RCT) over five months, two consultation and multidisciplinary treatments during three months (one RCT), to six to eight individual or group sessions over six months (also one RCT). All participants were recruited through rheumatology clinics, both in or outside hospitals. Included trials investigated job loss (n = two RCTs; 382 participants), work absenteeism and work functioning (n = one RCT; 32 participants). Overall, we evaluated the two smaller trials as having a high risk of bias and the large trial as having a low risk of bias. Trials showed marked differences in how they performed on risk of bias items, particularly on performance bias. We assessed the quality of the evidence using the GRADE approach and judged there to be very low quality evidence across the three reported outcomes. Of the two RCTs investigating job loss, the larger one (n = 242 participants) reported a large statistically significant reduction in job loss (relative risk (RR) = 0.35, 95% confidence interval (CI) 0.18 to 0.68) and the other RCT (n = 140) reported similar effects in both groups, although the CI was very wide (RR = 1.05, 95% CI 0.53 to 2.06). The latter one probably suffered from performance bias and we judged it to have a high risk of bias. The one small trial investigating sickness absenteeism found uncertain results at six months' follow-up (MD = -2.42 days, 95% CI -5.03 to 0.19). Finally, in the same small trial investigating work functioning using the Rheumatoid Arthritis-Work Instability Scale (RA-WIS), there was a moderate improvement of intermediate term work functioning (six months; scale range 0 to 23; mean improvement -4.67 points, 95% CI -8.43 to -0.91). We identified no adverse effects in the publications of the three trials. Authors' conclusions This Cochrane review of three RCTs found very low quality evidence overall for job loss prevention interventions having an effect on job loss, work absenteeism and work functioning in workers with inflammatory arthritis. While this review highlights that further high quality RCTs are required, the results suggest that these strategies have potential to be effective.Cochrane database of systematic reviews (Online) 11/2014; 11(11):CD010208. DOI:10.1002/14651858.CD010208.pub2 · 5.70 Impact Factor