The Journal Of Rheumatology. Supplement[JOURNAL]
Sun
200 papers
Safety of nonsteroidal antiinflammatory drugs and/or paracetamol in people receiving methotrexate for inflammatory arthritis: a Cochrane systematic review.
Colebatch AN, Marks JL, van der Heijde DM … +1 more , Edwards CJ
J Rheumatol Suppl · 2012 Sep · PMID 22942332 · Publisher ↗
OBJECTIVE: To systematically review the literature on the safety of using nonsteroidal antiinflammatory drugs (NSAID) and/or paracetamol in people receiving methotrexate (MTX) for inflammatory arthritis (IA), as an evide...
OBJECTIVE: To systematically review the literature on the safety of using nonsteroidal antiinflammatory drugs (NSAID) and/or paracetamol in people receiving methotrexate (MTX) for inflammatory arthritis (IA), as an evidence base for generating clinical practice recommendations. METHODS: A systematic literature review was performed using the Cochrane Library, Medline, Embase, and conference proceedings for the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) for 2008-2009. The search aimed to identify studies describing adverse events (AE) with the concurrent use of paracetamol and/or NSAID in people taking MTX for IA. Articles fulfilling our predefined inclusion criteria were systematically reviewed and quality appraised. RESULTS: Seventeen publications out of 8681 identified studies were included in the review, all of which included people with rheumatoid arthritis (RA) using various NSAID; there were no identified studies for other forms of IA or with paracetamol. Of the studies examining concurrent use of MTX and NSAID, there were no reported adverse effects on lung, liver, or renal function, and no increase in MTX withdrawal or in major toxic reactions. However, transient thrombocytopenia was demonstrated in 1 study. Looking at specific NSAID, there were no clinically significant AE with concomitant piroxicam or etodolac, and only mild AE with celecoxib or etoricoxib. Antiinflammatory dose aspirin was demonstrated to have an adverse effect on liver and renal function. CONCLUSION: In the management of RA, concurrent use of NSAID with MTX appears to be safe, provided appropriate monitoring is performed. The use of antiinflammatory doses of aspirin should be avoided.
Safety of pain therapy during pregnancy and lactation in patients with inflammatory arthritis: a systematic literature review.
Adams K, Bombardier C, van der Heijde DM
J Rheumatol Suppl · 2012 Sep · PMID 22942331 · Publisher ↗
OBJECTIVE: To systematically review the safety of various pain therapies used during pregnancy and lactation in patients with inflammatory arthritis. METHODS: A systematic literature review was performed in Medline, Emba...
OBJECTIVE: To systematically review the safety of various pain therapies used during pregnancy and lactation in patients with inflammatory arthritis. METHODS: A systematic literature review was performed in Medline, Embase, the Cochrane Library, and the American College of Rheumatology/European League Against Rheumatism 2008-2009 meeting abstracts, as part of the multinational 3e (Evidence, Expertise, Exchange) Initiative for generating practical recommendations about Pain Management by Pharmacotherapy in Inflammatory Arthritis. Articles fulfilling predefined inclusion criteria were reviewed, and quality appraisal was performed. RESULTS: The search yielded a total of 3974 articles and 7 abstracts. The only study that fulfilled the criteria for pain therapies in pregnancy was a systematic review published in 2008, evaluating the effects of nonsteroidal antiinflammatory drug (NSAID) use during pregnancy in patients with rheumatic conditions. Two of the 3 studies reviewed in the 2008 publication could be included in our current review. No studies were included in the review in relation to lactation. A total of 204 malformations were identified among infants exposed to NSAID, with an OR of 1.04. The number of identified cardiac defects was higher than expected, with an OR of 1.86. There seemed to be no specificity for the type of NSAID used. Among the 6 infants with orofacial clefts, 5 occurred with naproxen use and 1 with ibuprofen. CONCLUSION: Only 2 studies evaluating the risk of NSAID use in patients with inflammatory arthritis were identified, with results suggesting a higher rate of cardiac malformations in infants exposed to NSAID during the first trimester. No studies evaluating the effects of other treatments, such as paracetamol, corticosteroids, muscle relaxants, neuromodulators, antidepressants, opioids, or opioid-like therapy in the specific context of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, or spondyloarthritis, and no studies with respect to lactation were identified. Research is needed to improve the risk-benefit ratio of the use of pain therapies for inflammatory arthritis during pregnancy.
Safety and efficacy of on-demand versus continuous use of nonsteroidal antiinflammatory drugs in patients with inflammatory arthritis: a systematic literature review.
Adams K, Bombardier C, van der Heijde D
J Rheumatol Suppl · 2012 Sep · PMID 22942330 · Publisher ↗
OBJECTIVE: To systematically review the efficacy and safety of on-demand versus continuous use of nonsteroidal antiinflammatory drugs (NSAID) in patients with inflammatory arthritis and to assess if longterm continuous t...
OBJECTIVE: To systematically review the efficacy and safety of on-demand versus continuous use of nonsteroidal antiinflammatory drugs (NSAID) in patients with inflammatory arthritis and to assess if longterm continuous treatment with NSAID in comparison with NSAID treatment on-demand reduces radiographic progression. METHODS: A systematic literature review was performed in Medline, Embase, the Cochrane Library, and American College of Rheumatology/European League Against Rheumatism 2008-2009 meeting abstracts as part of the multinational 3e (Evidence, Expertise, Exchange) Initiative for generating practical recommendations about Pain Management by Pharmacotherapy in Inflammatory Arthritis. Articles fulfilling predefined inclusion criteria were reviewed and quality appraisal was performed. RESULTS: The search yielded a total of 1410 articles from Medline and Embase, 73 from Cochrane Central, and 3 meeting abstracts. After review, only one study fulfilled the defined inclusion criteria, which indicated that longterm continuous treatment with NSAID versus NSAID treatment on-demand reduced radiographic progression in patients with ankylosing spondylitis. Secondary measured endpoints were disease activity measures including pain and the frequency of observed adverse events in both groups. Relevant adverse events tended to occur more frequently in the continuous treatment group with odds ratios of 2.79 for hypertension, 1.67 for abdominal pain, 1.35 for diarrhea, 0.95 for dyspepsia, and 3.2 for depression. None of these differences were statistically significant, with the exception of depression, which could not be explained. CONCLUSION: Based on a single study, there does not seem to be a statistical difference in efficacy between the on-demand versus continuous use of NSAID in the context of ankylosing spondylitis. There were no studies in patients with rheumatoid arthritis, psoriatic arthritis, or spondyloarthritis. Research is needed to study the risk-benefit ratio of continuous versus on-demand use of NSAID.
Combination therapy for pain management in inflammatory arthritis: a Cochrane systematic review.
Ramiro S, Radner H, van der Heijde DM … +3 more , Buchbinder R, Aletaha D, Landewé RB
J Rheumatol Suppl · 2012 Sep · PMID 22942329 · Publisher ↗
OBJECTIVE: To assess the efficacy and safety of combination pain therapy for people with inflammatory arthritis (IA). METHODS: Systematic review of randomized controlled trials using Cochrane Collaboration methodology. C...
OBJECTIVE: To assess the efficacy and safety of combination pain therapy for people with inflammatory arthritis (IA). METHODS: Systematic review of randomized controlled trials using Cochrane Collaboration methodology. Combination therapy was defined as at least 2 drugs from the following classes: analgesics, nonsteroidal antiinflammatory drugs (NSAID), opioids, opioid-like drugs, and neuromodulators (antidepressants, anticonvulsants, and muscle relaxants). The main efficacy and safety outcomes were pain and withdrawals due to adverse events, respectively. RESULTS: Twenty-three trials (total of 912 patients) met inclusion criteria [22 in rheumatoid arthritis (RA) and 1 in a mixed population of RA and osteoarthritis]. All except 1 were published before 1990. All trials were at high risk of bias, and heterogeneity precluded metaanalysis. Statistically significant differences between treatment groups were reported in only 5/23 (22%) trials: in 3 trials combination therapy was better (2 trials with NSAID + analgesic versus NSAID only and 1 trial with 2 NSAID versus 1 NSAID), in 1 trial combination therapy was worse (opioid + neuromodulator versus opioid only), and in the fifth trial (NSAID + analgesic versus NSAID alone) reported results were mixed depending on the dosage used in the monotherapy arm. In general, there were no differences in safety and withdrawals due to inadequate analgesia between combination and monotherapy. CONCLUSION: Based on 23 trials, all at high risk of bias, there is insufficient evidence to establish the value of combination therapy over monotherapy for pain management in IA. Well-designed trials are needed to address this question.
The efficacy and safety of opioids in inflammatory arthritis: a Cochrane systematic review.
Whittle SL, Richards BL, van der Heijde DM … +1 more , Buchbinder R
J Rheumatol Suppl · 2012 Sep · PMID 22942328 · Publisher ↗
OBJECTIVE: To determine the efficacy and safety of opioid analgesics in inflammatory arthritis (IA). METHODS: We searched Medline, Embase, and Central to May 2010. Randomized controlled trials in adults with IA that comp...
OBJECTIVE: To determine the efficacy and safety of opioid analgesics in inflammatory arthritis (IA). METHODS: We searched Medline, Embase, and Central to May 2010. Randomized controlled trials in adults with IA that compared opioids (administered via any route) to another intervention or placebo were included. Studies in the immediate postoperative setting were excluded. Two authors independently extracted data and assessed risk of bias. Primary endpoints were pain and adverse events (AE). Categorical data were pooled using RevMan5 and reported as relative risks (RR) or odds ratios (OR) with 95% confidence intervals (95% CI). RESULTS: Eleven studies were included, all in patients with RA. The risk of bias of all studies was high. No study was longer than 6 weeks in duration and 4 studies used single doses of study drugs. Seven studies were between 1 and 6 weeks in duration and assessed 6 different oral opioids. Only 1 study investigated a strong opioid. Data could be pooled from 4 studies comparing weak opioids to placebo: there was no difference in withdrawals due to inadequate analgesia (RR 0.82, 95% CI 0.34, 2.01), but patient-reported global impression of change was superior with opioids (RR 1.44, 95% CI 1.03, 2.03). Opioids were more likely than placebo to cause AE (OR 3.90, 95% CI 2.31, 6.56). There was no difference between opioids and placebo in net efficacy after adjustment for AE. CONCLUSION: Based on 11 heterogeneous studies of short duration and high risk of bias, there is weak evidence that opioids are effective analgesics in RA. AE are common and may offset the benefits. The relative risks and benefits of opioids in IA beyond 6 weeks are unknown.
The efficacy and safety of muscle relaxants in inflammatory arthritis: a Cochrane systematic review.
Richards BL, Whittle SL, van der Heijde DM … +1 more , Buchbinder R
J Rheumatol Suppl · 2012 Sep · PMID 22942327 · Publisher ↗
OBJECTIVE: To determine the efficacy and safety of muscle relaxants in pain management in patients with inflammatory arthritis (IA). METHODS: We searched the Cochrane Central Register of Controlled Trials, Medline, Embas...
OBJECTIVE: To determine the efficacy and safety of muscle relaxants in pain management in patients with inflammatory arthritis (IA). METHODS: We searched the Cochrane Central Register of Controlled Trials, Medline, Embase, and PsychINFO for randomized controlled trials in adults with IA that compared any muscle relaxant (administered via any route) to another analgesic intervention or placebo. We also searched the 2008-2009 American College of Rheumatology and European League Against Rheumatism abstracts and performed a hand search of reference lists of relevant articles. Primary outcomes were patient-reported pain relief ≥ 30% and withdrawals due to adverse events. Two authors independently assessed methodological quality and extracted data. RESULTS: Six trials (126 participants) were included in this review. All trials were deemed to have a high risk of bias. Five crossover trials evaluated benzodiazepine; 4 assessed diazepam (n = 71), and one assessed triazolam (n = 15). The sixth trial, a parallel-group study, evaluated zopiclone (non-benzodiazepine, n = 40). No trial was longer than 2 weeks and 3 single-dose trials assessed outcomes at 24 hours only. Overall, the included trials failed to find evidence of a beneficial effect of muscle relaxants over placebo (at 24 hours, 1 week, or 2 weeks) or in addition to nonsteroidal antiiflammatory drugs (at 24 hours) on pain intensity, function, or quality of life. Data from 2 trials of longer than 24-hour duration (diazepam and zopiclone, n = 74) found that participants who received a muscle relaxant had significantly more adverse events compared with those who received placebo [number needed to harm (NNTH) 3, 95% CI 2 to 7]. These were predominantly central nervous system side effects including dizziness and drowsiness (NNTH 3, 95% CI 2 to 11). CONCLUSION: Based upon the currently available evidence in patients with IA, benzodiazepines (diazepam and triazolam) do not appear to be beneficial in improving pain over 24 hours or 1 week. The non-benzodiazepine agent zopiclone also did not significantly reduce pain over 2 weeks. However, even short-term muscle relaxant use (24 hours to 2 weeks) is associated with significant adverse events, predominantly drowsiness and dizziness.
Efficacy and safety of neuromodulators in inflammatory arthritis: a Cochrane systematic review.
Richards BL, Whittle SL, van der Heijde DM … +1 more , Buchbinder R
J Rheumatol Suppl · 2012 Sep · PMID 22942326 · Publisher ↗
OBJECTIVE: To determine the efficacy and safety of neuromodulators for pain management in patients with inflammatory arthritis. METHODS: A Cochrane systematic review was performed as part of the 3e Initiative on pain man...
OBJECTIVE: To determine the efficacy and safety of neuromodulators for pain management in patients with inflammatory arthritis. METHODS: A Cochrane systematic review was performed as part of the 3e Initiative on pain management in inflammatory arthritis. We searched Medline, Embase, and Cochrane Central for studies to November 2010, and American College of Rheumatology/European League Against Rheumatism meeting abstracts published in 2008-2009. Studies were included if they were randomized or quasirandomized controlled trials that compared any neuromodulator (excluding cannabis) to another therapy (active or placebo, including nonpharmacological therapies) for pain in patients with RA, psoriatic arthritis, ankylosing spondylitis, or spondyloarthritis. Primary outcomes of interest were patient-reported pain relief of 30% or greater and withdrawals due to adverse events. Two authors independently extracted data and assessed methodological quality. A risk of bias assessment was performed using the methods recommended by the Cochrane Collaboration. RESULTS: Three trials, all in RA and all at high risk of bias, were included in this review. Two placebo-controlled trials evaluated nefopam (52 participants) and one placebo-controlled trial evaluated topical capsaicin 0.025% (31 participants). Pooled analysis showed a significant reduction in pain levels favoring nefopam over placebo after 2 weeks [weighted mean difference -21.2, 95% CI -35.6 to -6.7; number needed to treat (NNT) 2, 95% CI 1.4 to 9.5]. However, nefopam was associated with significantly more adverse events (RR 4.1, 95% CI 1.6 to 10.7; number needed to harm 9, 95% CI 2 to 367), predominantly nausea and sweating. In one trial, capsaicin reduced pain more than placebo at 1 and 2 weeks (MD -23.8, 95% CI -44.8 to -2.8; NNT 3, 95% CI 2-47, and -34.4, 95% CI -54.7 to -14.14; NNT 2, 95% CI 1.4 to 6, respectively). Of those who received capsaicin, 44% developed burning at the site of application and 2% withdrew as a result. CONCLUSION: Based on 3 small trials, which were all at high risk of bias, there is weak evidence that nefopam and capsaicin are superior to placebo in reducing pain in patients with RA, but both are associated with a significant side effect profile. There are no available data for other types of IA or for newer agents such as gabapentin or pregabalin.
The efficacy and safety of antidepressants in inflammatory arthritis: a Cochrane systematic review.
Richards BL, Whittle SL, van der Heijde DM … +1 more , Buchbinder R
J Rheumatol Suppl · 2012 Sep · PMID 22942325 · Publisher ↗
OBJECTIVES: To determine the efficacy and safety of antidepressants in pain management in patients with inflammatory arthritis (IA). METHODS: We searched the Cochrane Central Register of Controlled Trials, Medline, Embas...
OBJECTIVES: To determine the efficacy and safety of antidepressants in pain management in patients with inflammatory arthritis (IA). METHODS: We searched the Cochrane Central Register of Controlled Trials, Medline, Embase, and PsychINFO for randomized controlled trials in adults with IA that compared any antidepressants (administered via any route) to another analgesic intervention or placebo. We also searched the 2008-2009 American College of Rheumatology and European League Against Rheumatism abstracts and performed a hand search of reference lists of relevant articles. Primary outcomes were patient-reported pain relief ≥ 30% and withdrawals due to adverse events. Two authors independently assessed methodological quality and extracted data. A risk of bias assessment was performed using methods recommended by the Cochrane Collaboration. RESULTS: Eight trials (652 participants) in patients with rheumatoid arthritis (RA) and 1 trial in patients with ankylosing spondylitis (100 participants) were included in this review. The majority of studies were published in the late 1980s in patients with active disease receiving minimal disease-modifying antirheumatic drug therapy. All trials evaluated tricyclic antidepressants (TCA) and 2 studies included a selective serotonin uptake inhibitor. Seven of the 9 trials had high risk of bias, 2 were unclear, and metaanalysis was not performed due to trial heterogeneity. RA trials with short-term outcome (< 1 week) found no significant benefit of amitriptyline 25 mg in combination with dextropropoxyphene (DXP) 65 mg over placebo, and inferiority of amitriptyline + DXP versus DXP 130 mg [mean difference (MD) 10.0, 95% CI 0.4 to 19.6]. There was conflicting evidence regarding medium (1-6 wks) or longer-term (> 6 wks) benefits on pain. One trial in depressed patients with RA showed no significant difference between amitriptyline and paroxetine given for 8 weeks (65% vs 56% much or very much improved; RR 1.2, 95% CI 0.9 to 1.5). One trial found that amitriptyline was no better than placebo in reducing pain in patients with active AS over 2 weeks (MD -0.2, 95% CI -1.2 to 0.8). From 5 trials, withdrawals due to adverse events were not significantly different from placebo. However, there were significantly more minor adverse events in patients receiving TCA compared with those receiving a placebo (RR 2.3, 95% CI 1.2 to 4.4). These included somnolence, dizziness, dry mouth, and nausea. CONCLUSION: Based upon 9 trials of high or unclear risk of bias, it is not possible to draw firm conclusions about the efficacy of TCA as analgesics for patients with IA. The use of these agents may be associated with adverse events that are generally mild and do not lead to cessation of treatment. High-quality trials are needed in this area.
The role of corticosteroids for pain relief in persistent pain of inflammatory arthritis: a systematic literature review.
Tarner IH, Englbrecht M, Schneider M … +2 more , van der Heijde DM, Müller-Ladner U
J Rheumatol Suppl · 2012 Sep · PMID 22942324 · Publisher ↗
OBJECTIVE: To conduct a systematic review of the available literature addressing the effectiveness, safety, and role of corticosteroids for pain relief in persistent pain of inflammatory arthritis (IA), as part of the in...
OBJECTIVE: To conduct a systematic review of the available literature addressing the effectiveness, safety, and role of corticosteroids for pain relief in persistent pain of inflammatory arthritis (IA), as part of the international 3e (Evidence, Expertise, Exchange) Initiative. METHODS: A systematic literature research (SLR) was carried out in Medline, Embase, the Cochrane Library, and the American College of Rheumatology/European League Against Rheumatism meeting abstracts, searching for studies evaluating the use of steroids for the treatment of residual pain in IA despite adequate antiinflammatory therapy. RESULTS: Of 3887 references retrieved by SLR, 2 randomized controlled studies and 35 review articles underwent full-text review. No article was found to adequately address the research question. CONCLUSION: No data on the efficacy and safety of systemic corticosteroids in residual pain in IA could be identified from the literature.
Paracetamol for the management of pain in inflammatory arthritis: a systematic literature review.
Hazlewood G, van der Heijde DM, Bombardier C
J Rheumatol Suppl · 2012 Sep · PMID 22942323 · Publisher ↗
OBJECTIVE: To systematically review the literature on the efficacy and safety of paracetamol (acetaminophen) in the management of pain in inflammatory arthritis. METHODS: A systematic search was performed in Medline, Emb...
OBJECTIVE: To systematically review the literature on the efficacy and safety of paracetamol (acetaminophen) in the management of pain in inflammatory arthritis. METHODS: A systematic search was performed in Medline, Embase, the Cochrane Library, and 2008/2009 American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) conference abstracts for clinical trials and observational studies of paracetamol in patients with inflammatory arthritis. Included trials were appraised for risk of bias, and relevant study details were abstracted. Efficacy was assessed from clinical trials using improvement in pain as the outcome measure, and safety was assessed using total adverse events and withdrawals due to adverse events as outcome measures. Safety data from observational studies were assessed separately. RESULTS: Eleven articles containing 12 clinical trials and 1 observational study were identified, all in patients with rheumatoid arthritis. The trials were of short duration, used atypical doses of paracetamol, and all had a high risk of bias. Overall, there was weak evidence of a benefit of paracetamol over placebo and an additive benefit of paracetamol in combination with nonsteroidal antiinflammatory drugs (NSAID). The benefit of paracetamol to NSAID alone was uncertain. No significant differences in safety were seen in the limited clinical trial data. One cohort study showed an increased rate of serious gastrointestinal events with paracetamol over NSAID when used concurrently with corticosteroids and other analgesics, but had significant methodological limitations. CONCLUSION: There is weak evidence for the efficacy of paracetamol in patients with inflammatory arthritis, and insufficient disease-specific safety data to draw conclusions.
Measuring pain and efficacy of pain treatment in inflammatory arthritis: a systematic literature review.
Englbrecht M, Tarner IH, van der Heijde DM … +3 more , Manger B, Bombardier C, Müller-Ladner U
J Rheumatol Suppl · 2012 Sep · PMID 22942322 · Publisher ↗
OBJECTIVE: To systematically review the available literature on measuring pain and the efficacy of pain treatment in inflammatory arthritis (IA), as an evidence base for generating clinical practice recommendations. METH...
OBJECTIVE: To systematically review the available literature on measuring pain and the efficacy of pain treatment in inflammatory arthritis (IA), as an evidence base for generating clinical practice recommendations. METHODS: A systematic literature search was performed in Medline, Embase, Cochrane Library, and the American College of Rheumatology/European League Against Rheumatism 2008/2009 meeting abstracts, searching for studies evaluating clinimetric properties of pain measurement tools in IA (convergent validity, internal consistency, retest reliability, responsiveness, feasibility, and standardization). Studies that presented information on these properties were reviewed and their data were integrated into the pool of results available for pain measures in IA. RESULTS: In total, 51 articles were included in the review. Validated information on pain was available for tools covering different facets such as overall pain, anatomically specific pain, or a mixture of both. Data from these studies showed that single pain-related items such as the visual analog scale (VAS), numeric rating scale (NRS), or verbal rating scale (VRS) provide sufficient clinimetric information. Similar results were obtained for the pain subscales of the Arthritis Impact Measurement Scales (AIMS/AIMS2) and the bodily pain subscale of the Medical Outcome Study Short-Form Survey 36. Most clinimetric coefficients showed acceptable results with respect to validity, reliability, and sensitivity to change, while the degree of standardization and feasibility mostly filled at least 2 of 3 predefined criteria. CONCLUSION: A variety of pain measures are available to cover different aspects of pain such as intensity, frequency, or location. Single-item tools such as VAS, NRS, or VRS can be recommended to measure overall pain in clinical practice. If more specific issues need to be addressed, more sophisticated tools should be taken into account.
Pain management by pharmacotherapy in inflammatory arthritis. Systematic literature reviews of the 3e Initiative 2010.
van der Heijde DM
J Rheumatol Suppl · 2012 Sep · PMID 22942321 · Publisher ↗
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Future trends in research in psoriatic arthritis.
Gladman DD
J Rheumatol Suppl · 2012 Jul · PMID 22751608 · Publisher ↗
Major advances have taken place in the study of psoriatic arthritis (PsA) in the past several decades. Future trends in research will likely be based on these advances and will span a wide spectrum of activities includin...
Major advances have taken place in the study of psoriatic arthritis (PsA) in the past several decades. Future trends in research will likely be based on these advances and will span a wide spectrum of activities including further refinement of disease definition and particularly disease pattern. More precise definitions for axial and peripheral disease and in particular arthritis mutilans will be necessary for further genetic and biomarker studies. Early definition of PsA is crucial. Future research will concentrate on identifying genetic and other biomarkers for early diagnosis, disease expression, disease progression, and comorbidities. Newer therapies will be developed as well.
Pharmacoeconomic issues in psoriatic arthritis.
Olivieri I, D'Angelo S, Palazzi C … +3 more , Padula A, Lubrano E, Mantovani LG
J Rheumatol Suppl · 2012 Jul · PMID 22751607 · Publisher ↗
Therapies for psoriatic arthritis were inadequate until a short time ago. Nonsteroidal antiinflammatory drugs are helpful in relieving symptoms but do not prevent joint damage. Traditional disease-modifying antirheumatic...
Therapies for psoriatic arthritis were inadequate until a short time ago. Nonsteroidal antiinflammatory drugs are helpful in relieving symptoms but do not prevent joint damage. Traditional disease-modifying antirheumatic drugs are used to control symptoms, but there is no evidence that they prevent or significantly slow the progression of structural damage in peripheral joints. The introduction of tumor necrosis factor-α (TNF-α) blocking agents has opened new horizons. These drugs lessen signs and symptoms of inflammation, enhance functional capacity and quality of life, and inhibit structural joint damage. On the other hand, TNF-α blockers are very costly and not easily available to all patients, whether they rely on a national health system or on private insurance. Pharmacoeconomic studies on these drugs so far have shown that they are cost-effective on both the musculoskeletal and skin manifestations of psoriatic disease, offering good value for money.
The inhibitor of costimulation of T cells: abatacept.
Iannone F, Lapadula G
J Rheumatol Suppl · 2012 Jul · PMID 22751606 · Publisher ↗
OBJECTIVE: T cell costimulation is a key point in the regulation of immune tolerance, immune response, and autoimmunity. T cell activation does not take place upon the simple engagement of T cell receptor; a second signa...
OBJECTIVE: T cell costimulation is a key point in the regulation of immune tolerance, immune response, and autoimmunity. T cell activation does not take place upon the simple engagement of T cell receptor; a second signal is needed to fully stimulate T cells. There are a variety of molecules that can act as costimulators, and among those CD28/CD80 signaling plays a crucial role in modulating T cell response. Cytotoxic T lymphocyte antigen-4, CD152 (CTLA4) is a physiologic antagonist of CD28, and abatacept, a synthetic analog of CTLA4, has recently been approved to treat rheumatoid arthritis. An abnormal T cell activation is also believed to sustain psoriatic disease both at skin and joint sites. We aimed to evaluate the rationale of blocking CD28/CD80 signaling and the possible use of abatacept for treating psoriatic arthritis (PsA). METHODS: We reviewed the role of CD28/CD80 signaling in promoting T cell inflammation in psoriasis and the effects of CTLA4 modulation in experimental models of psoriasis and in humans. RESULTS: CD28/CD80 seems to be crucial in stimulating T cell activation and inflammation in psoriasis, and its inhibition by CTLA4 analogs or by anti-CD28 blocking antibodies is effective against psoriasis. Few data are available on abatacept, which seems to be valuable for the treatment of PsA but less useful in the therapy of skin psoriasis. CONCLUSION: Although the CD28 molecule is crucial in activating T cells and inflammation in psoriasis, data on the efficacy of abatacept in the treatment of PsA are still not conclusive.
Interleukin 6 blockade: tocilizumab in psoriatic arthritis.
Atzeni F, Ventura D, Batticciotto A … +2 more , Boccassini L, Sarzi-Puttini P
J Rheumatol Suppl · 2012 Jul · PMID 22751605 · Publisher ↗
Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy of unknown etiology that is associated with psoriasis. Joint destruction is often progressive: almost half of the patients attending an early arthritis clin...
Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy of unknown etiology that is associated with psoriasis. Joint destruction is often progressive: almost half of the patients attending an early arthritis clinic showed radiological damage 2 years after diagnosis. Proinflammatory cytokines are major mediators of systemic and local inflammation, and high levels of interleukin 1 (IL-1), IL-6, and tumor necrosis factor have been found in psoriatic skin lesions and the synovial tissue of patients with rheumatoid arthritis and PsA. IL-6 is a pleiotropic cytokine that mainly signals by membrane (neutrophil and lymphocyte) or soluble (endothelial cell) IL-6 receptors. IL-6 was originally identified as a factor in B cell differentiation, but is now known to influence T cell development: in the presence of IL-6 and transforming growth factor-ß (TGF-ß), naive T cells develop into Th17 cells, which are important mediators in PsA. IL-6 may also directly contribute to the epidermal hyperplasia seen in psoriatic epithelium and affect the function of dermal inflammatory cells. However, there are no data concerning the use of tocilizumab in patients with PsA, although a pilot study is currently being carried out because the role of IL-6 in the pathogenesis of PsA supports the idea that targeted treatments against IL-6 might be effective.
Should we consider tumor necrosis factor as the only target in spondyloarthritides?
Ferraccioli G, Gremese E
J Rheumatol Suppl · 2012 Jul · PMID 22751604 · Publisher ↗
Understanding the biology of inflammation occurring at the entheseal-bone insertion has led to a better knowledge of the main drivers of inflammation in spondyloarthropathies. The clinical efficacy of tumor necrosis fact...
Understanding the biology of inflammation occurring at the entheseal-bone insertion has led to a better knowledge of the main drivers of inflammation in spondyloarthropathies. The clinical efficacy of tumor necrosis factor-α (TNF-α) blockers strongly supports the idea that TNF-α is a key molecule. Yet 40% of patients do not respond appropriately, indicating that other pathways are likely involved in these illnesses. Targeting T cells through a blockade of costimulating (CD28) molecules does not help, and in experimental models of sacroiliitis, targeting interleukin 6 (IL-6) did not provide any useful evidence. Immunohistological and functional data suggest that B cells, Th17, or IL-17A might be important, and indeed preliminary data concerning drugs targeting B cells and IL-17A seem to suggest clinical benefits.
Treatment of psoriatic arthritis with tumor necrosis factor inhibitors: longer-term outcomes including enthesitis and dactylitis with golimumab treatment in the Longterm Extension of a Randomized, Placebo-controlled Study (GO-REVEAL).
Kavanaugh A, Mease P
J Rheumatol Suppl · 2012 Jul · PMID 22751603 · Publisher ↗
OBJECTIVE: To assess longer-term outcomes, including enthesitis and dactylitis, in patients with active psoriatic arthritis (PsA), in a study of golimumab treatment. METHODS: Adult patients with active PsA were randomize...
OBJECTIVE: To assess longer-term outcomes, including enthesitis and dactylitis, in patients with active psoriatic arthritis (PsA), in a study of golimumab treatment. METHODS: Adult patients with active PsA were randomized to receive subcutaneous injections of placebo (n = 113), golimumab 50 mg (n = 146), or golimumab 100 mg (n = 146) every 4 weeks through Week 20. All patients received golimumab 50 mg or 100 mg from Week 24 onward. Entheses tenderness was scored in 15 body sites using the PsA-modified Maastricht Ankylosing Spondylitis Enthesitis Score (MASES). Dactylitis was assessed in 20 digits of the hands and feet. RESULTS: Among the 405 randomized patients, 77% presented with enthesitis and 34% dactylitis at baseline. At Week 24 of the placebo-controlled study phase, significant differences were observed between golimumab 50 mg and/or 100 mg and placebo for mean percent improvement in the PsA-modified MASES [46% (p < 0.001) and 52% (p < 0.001) vs 13%, respectively] and the dactylitis score [66% (p = 0.09) and 82% (p < 0.001) vs 28%, respectively]. By Week 52, improvements were maintained among patients randomized to receive golimumab (mean improvements of 54% for PsA-modified MASES and 77% for the dactylitis score). Those given placebo who had enthesitis or dactylitis at baseline and who crossed over to golimumab at Week 16 or 24 had somewhat less improvement at Week 52 (i.e., 39% for the PsA-modified MASES, 57% for dactylitis score). CONCLUSION: Treatment of PsA patients with the TNF inhibitor golimumab was effective across all components of disease, including enthesitis and dactylitis, and efficacy was maintained over longer-term followup.
Ustekinumab for psoriasis and psoriatic arthritis.
Goldminz AM, Gottlieb AB
J Rheumatol Suppl · 2012 Jul · PMID 22751602 · Publisher ↗
Ustekinumab, which is approved for the treatment of moderate to severe psoriasis, has been shown in phase II clinical trials to be efficacious in controlling the signs and symptoms of psoriatic arthritis. Ustekinumab app...
Ustekinumab, which is approved for the treatment of moderate to severe psoriasis, has been shown in phase II clinical trials to be efficacious in controlling the signs and symptoms of psoriatic arthritis. Ustekinumab appears to be well tolerated, but its longterm safety profile is not yet known.
Screening and monitoring of latent tubercular infection in patients taking tumor necrosis factor-α blockers for psoriatic arthritis.
Sanduzzi A, Bocchino M, Atteno M … +9 more , Costa L, Ponticiello A, Matarese A, Spanò A, Bruner V, Peluso R, Aquino MM, Del Puente A, Scarpa R
J Rheumatol Suppl · 2012 Jul · PMID 22751601 · Publisher ↗
Patients with arthritis who need treatment with biologics are carefully screened for possible previous exposure to tuberculosis to detect any latent tubercular infection (LTBI). The traditional method of screening for LT...
Patients with arthritis who need treatment with biologics are carefully screened for possible previous exposure to tuberculosis to detect any latent tubercular infection (LTBI). The traditional method of screening for LTBI is not specific, because positivity could also depend on infection by atypical mycobacteria and bacillus Calmette-Guerin vaccination. In addition, the screening does not show high sensitivity, frequently presenting a false negativity because of immunosuppression caused by drugs used for arthritis. Recently, interferon-γ release assays (IGRA) have been used to screen LTBI with more sensitivity and specificity before treatment with anti-tumor necrosis factor-α drugs. Moreover, in our experience, IGRA are potentially useful in monitoring LTBI during biologic therapy.
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