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Annals of the Rheumatic Diseases Jun 2020To perform an update of a review of the efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) in psoriatic arthritis (PsA).
Pharmacological treatment of psoriatic arthritis: a systematic literature research for the 2019 update of the EULAR recommendations for the management of psoriatic arthritis.
OBJECTIVE
To perform an update of a review of the efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) in psoriatic arthritis (PsA).
METHODS
This is a systematic literature research of 2015-2018 publications on all DMARDs in patients with PsA, searching Medline, Embase and the Cochrane Library. Efficacy was assessed in randomised controlled trials. For safety, cohort studies, case-control studies and long-term extensions (LTEs) were analysed.
RESULTS
56 publications (efficacy: n=33; safety n=23) were analysed. The articles were on tumour necrosis factor (TNF) inhibitors (n=6; golimumab, etanercept and biosimilars), interleukin (IL)-17A inhibitors (n=10; ixekizumab, secukinumab), IL-23-p19 inhibitors (n=2; guselkumab, risankizumab), clazakizumab (IL-6 inhibitor), abatacept (CD80/86 inhibitor) and ABT-122 (anti-TNF/IL-17A), respectively. One study compared ustekinumab (IL-12/23i) with TNF inhibitor therapy in patients with entheseal disease. Three articles investigated DMARD tapering. Trials on targeted synthetic DMARDs investigated apremilast (phosphodiesterase-4 inhibitor) and Janus kinase inhibitors (JAKi; tofacitinib, filgotinib). Biosimilar comparison with bio-originator showed non-inferiority. Safety was evaluated in 13 LTEs, 9 cohort studies and 1 case-control study investigating malignancies, infections, infusion reactions, multiple sclerosis and major cardiovascular events, as well as efficacy and safety of vaccination. No new safety signals were identified; however, warnings on the risk of venous thromboembolic events including pulmonary embolism when using JAKi were issued by regulators based on other studies.
CONCLUSION
Many drugs in PsA are available and have demonstrated efficacy against placebo. Efficacy varies across PsA manifestations. Safety must also be taken into account. This review informed the development of the European League Against Rheumatism 2019 updated PsA management recommendations.
Topics: Antirheumatic Agents; Arthritis, Psoriatic; Biological Products; Humans; Interleukin-17; Interleukin-23 Subunit p19; Molecular Targeted Therapy; Synthetic Drugs; Tumor Necrosis Factor-alpha
PubMed: 32381564
DOI: 10.1136/annrheumdis-2020-217163 -
PloS One 2019Our objective was to compare the cardiovascular safety of tocilizumab and other biological disease-modifying antirheumatic drugs (bDMARD) in rheumatoid arthritis using a... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Our objective was to compare the cardiovascular safety of tocilizumab and other biological disease-modifying antirheumatic drugs (bDMARD) in rheumatoid arthritis using a network meta-analysis (NMA).
METHODS
A systematic literature search through May 2018 identified randomized controlled trials (RCT) or observational studies (cohort only) reporting cardiovascular outcomes of tocilizumab (TCZ) and/or abatacept (ABA) and/or rituximab (RTX) and/or tumor necrosis factor inhibitors (TNFi) in rheumatoid arthritis patients. The composite primary outcome was the rate of major adverse cardiovascular outcomes (MACE, myocardial infarction (MI), peripheral artery disease (PAD) and cardiac heart failure (CHF)).
RESULTS
19 studies were included in the NMA, including 11 RCTs and 8 cohort studies. We found less events with RTX (5.41 [1.70;17.26]. We found no difference between TCZ and other treatments. Concerning MI, we found no difference between TCZ and csDMARD (4.23 [0.22;80.64]), no difference between TCZ and TNFi (2.00 [0.18;21.84]). There was no difference between TCZ and csDMARD (1.51[0.02;103.50] and between TCZ and TNFi (1.00 [0.06;15.85]) for stroke event. With cohorts and RCT NMA, we found no difference between TCZ and other treatments for MACE (0.66 [0.42;1.03] with ABA, 1.04 [0.60;1.81] with RTX, 0.78[0.53;1.16] and 0.91 [0.54;1.51] with csDMARD), but the risk of myocardial infarction was lower with TCZ compared to ABA (0.67 [0.47;0.97]). We lacked data to compare TCZ and other bDMARD for stoke and MI. Not enough data was available to perform a NMA for CHF and PAD.
CONCLUSIONS
Despite an increase in cholesterol levels, TCZ has safe cardiovascular outcomes compared to other bDMARD.
Topics: Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Arthritis, Rheumatoid; Cardiovascular Diseases; Humans; Network Meta-Analysis; Patient Safety; Prognosis
PubMed: 31369575
DOI: 10.1371/journal.pone.0220178 -
European Review For Medical and... Jan 2021We aimed to systematically review biological agents' efficacy and safety in patients with Takayasu arteritis (TAK). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
We aimed to systematically review biological agents' efficacy and safety in patients with Takayasu arteritis (TAK).
MATERIALS AND METHODS
A systematic literature search of 7 electronic databases, including MEDLINE (via PubMed), EMBASE, Elsevier ScienceDirect, EBSCO, Springer Link, Web of Science, and Cochrane Library on the efficacy of biological agents on patients with TAK was conducted. Only studies published in English and with a sample size >5 patients with TAK were included. Two reviewers independently selected studies, extracted data and assessed its methodological quality. Random effects meta-analyses of various effect measures were performed.
RESULTS
According to the title and abstract, 961 studies were identified and screened. Subsequently, 31 studies from 29 observational studies and 2 randomized-controlled trials (RCTs), which included a total of 517 patients with TAK that met the inclusion and exclusion criteria, were selected. Observational studies showed a high risk of bias. Pooled remission rates of biological agents were 66% (95% CI: 58%-73%; I2=59%), and the remission rates of anti-tumor necrosis factor (TNF) agents and tocilizumab (TCZ) were similar: 65% (95% CI: 56%-73%; I2=49%) and 70% (95% CI: 55%-86%; I2=69%), respectively. Pooled relapse rates were 23% (95% CI: 15%-31%; I2=66%). The relapse rate was 28% (95% CI: 16%-40%; I2=68%) for anti-TNF agents and 17% (95% CI: 7%-26%; I2=49%) for TCZ. The remission rate of TCZ was slightly higher (p>0.05), but the relapse rate was statistically significantly lower than that of anti-TNF agents (p=0.017). Furthermore, biological agents significantly decreased the doses of glucocorticoid (GC) and levels of acute phase inflammation markers (ESR, CRP) while the proportion of patients with new angiographic lesions or progression of previously noted lesions were 11% (95% CI: 4%-18%; I2=59%). RCTs with a small sample size showed abatacept was ineffective, and TCZ was underpowered to detect a difference in time to relapse compared to placebo. The most common adverse event of biological agents was infection (6%, 95%CI: 2%-10%). No deaths were reported.
CONCLUSIONS
Although the beneficial effects of biological agents are encouraging in enhancing disease remission, reducing the levels of acute phase inflammation markers and decreasing the treatment doses of GC in patients with TAK, there is still a risk of relapse. More refined studies with larger cohorts are necessary before drawing a definitive opinion.
Topics: Biological Factors; Humans; Takayasu Arteritis
PubMed: 33506914
DOI: 10.26355/eurrev_202101_24391 -
The Cochrane Database of Systematic... Jun 2016Fatigue is a common and potentially distressing symptom for patients with rheumatoid arthritis (RA), with no accepted evidence-based management guidelines. Evidence... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fatigue is a common and potentially distressing symptom for patients with rheumatoid arthritis (RA), with no accepted evidence-based management guidelines. Evidence suggests that biologic interventions improve symptoms and signs in RA as well as reducing joint damage.
OBJECTIVES
To evaluate the effect of biologic interventions on fatigue in rheumatoid arthritis.
SEARCH METHODS
We searched the following electronic databases up to 1 April 2014: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Current Controlled Trials Register, the National Research Register Archive, The UKCRN Portfolio Database, AMED, CINAHL, PsycINFO, Social Science Citation Index, Web of Science, and Dissertation Abstracts International. In addition, we checked the reference lists of articles identified for inclusion for additional studies and contacted key authors.
SELECTION CRITERIA
We included randomised controlled trials if they evaluated a biologic intervention in people with rheumatoid arthritis and had self reported fatigue as an outcome measure.
DATA COLLECTION AND ANALYSIS
Two reviewers selected relevant trials, assessed methodological quality and extracted data. Where appropriate, we pooled data in meta-analyses using a random-effects model.
MAIN RESULTS
We identified 32 studies for inclusion in this current review. Twenty studies evaluated five anti-tumour necrosis factor (anti-TNF) biologic agents (adalimumab, certolizumab, etanercept, golimumab and infliximab), and 12 studies focused on five non-anti-TNF biologic agents (abatacept, canakinumab, rituximab, tocilizumab and an anti-interferon gamma monoclonal antibody). All but two of the studies were double-blind randomised placebo-controlled trials. In some trials, patients could receive concomitant disease-modifying anti-rheumatic drugs (DMARDs). These studies added either biologics or placebo to DMARDs. Investigators did not change the dose of the latter from baseline. In total, these studies included 9946 participants in the intervention groups and 4682 participants in the control groups. Overall, quality of randomised controlled trials was moderate with a low to unclear risk of bias in the reporting of the outcome of fatigue. We downgraded the quality of the studies from high to moderate because of potential reporting bias (studies included post hoc analyses favouring reporting of positive result and did not always include all randomised individuals). Some studies recruited only participants with early disease. The studies used five different instruments to assess fatigue in these studies: the Functional Assessment of Chronic Illness Therapy Fatigue Domain (FACIT-F), Short Form-36 Vitality Domain (SF-36 VT), Visual Analogue Scale (VAS) (0 to 100 or 0 to 10) and the Numerical Rating Scale (NRS). We calculated standard mean differences for pooled data in meta-analyses. Overall treatment by biologic agents led to statistically significant reduction in fatigue with a standardised mean difference of -0.43 (95% confidence interval (CI) -0.38 to -0.49). This equates to a difference of 6.45 units (95% CI 5.7 to 7.35) of FACIT-F score (range 0 to 52). Both types of biologic agents achieved a similar level of improvement: for anti-TNF agents, this stood at -0.42 (95% CI -0.35 to -0.49), equivalent to 6.3 units (95% CI 5.3 to 7.4) on the FACIT-F score; and for non-anti-TNF agents, it was -0.46 (95% CI -0.39 to -0.53), equivalent to 6.9 units (95% CI 5.85 to 7.95) on the FACIT-F score. In most studies, the double-blind period was 24 weeks or less. No study assessed long-term changes in fatigue.
AUTHORS' CONCLUSIONS
Treatment with biologic interventions in patients with active RA can lead to a small to moderate improvement in fatigue. The magnitude of improvement is similar for anti-TNF and non-anti-TNF biologics. However, it is unclear whether the improvement results from a direct action of the biologics on fatigue or indirectly through reduction in inflammation, disease activity or some other mechanism.
Topics: Abatacept; Adalimumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Arthritis, Rheumatoid; Certolizumab Pegol; Etanercept; Fatigue; Humans; Immunosuppressive Agents; Infliximab; Interferon-gamma; Randomized Controlled Trials as Topic; Rituximab
PubMed: 27271314
DOI: 10.1002/14651858.CD008334.pub2 -
Pharmaceutics Oct 2022The prevention of joint deformity is among the most important treatment goals of psoriatic arthritis. Some biologics disease-modifying antirheumatic drugs (bDMARDs) have... (Review)
Review
The prevention of joint deformity is among the most important treatment goals of psoriatic arthritis. Some biologics disease-modifying antirheumatic drugs (bDMARDs) have been demonstrated to be effective for both the skin and joints, as well as for slowing radiographic progression. However, there has been a lack of direct comparisons of bDMARDs. To evaluate the comparative effects of bDMARDs in preventing radiographic progression in psoriatic arthritis, we conducted a systematic review and network meta-analysis. On March 7 2022, a search for relevant randomized trials was conducted on MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials. Our outcomes included radiographic non-progression, a mean change in the total radiographic score, and adverse events leading to discontinuation (DAE) at week 24. We included 11 trials on 10 bDMARDs, involving 4010 participants. Most bDMARDs were more effective than placebos in achieving radiographic non-progression, including adalimumab (odds ratio (OR) 4.7, 95% confidence interval (CI) 2.66-8.29), etanercept (OR 4.19, 95% CI 1.65-10.61), certolizumab pegol (OR 2.83, 95% CI 1.55-5.2), secukinumab 300 mg (OR 2.63, CI 1.62-4.27), infliximab (OR 2.54, CI 1.13-5.69), ixekizumab (OR 2.22, 95% CI 1.06-4.65), golimumab (OR 2.21, 95% CI 1.24-3.93), and abatacept (OR 1.54, 95% CI 1.03-2.28). A significant reduction in the total radiographic score was found in infliximab (standardized mean difference (SMD) -0.59, 95% CI -0.87, -0.3), etanercept (SMD -0.51, 95% CI -0.78, -0.23), adalimumab (SMD -0.45, 95% CI -0.64, -0.26), ixekizumab (SMD -0.37, 95% CI -0.62, -0.12), secukinumab 300 mg (SMD -0.33, 95% CI -0.50, -0.15), golimumab (SMD -0.33, 95% CI -0.58, -0.09), secukinumab 150 mg (SMD -0.25, 95% CI -0.43, -0.07), certolizumab pegol (SMD -0.23, 95% CI -0.44, -0.03), and ustekinumab (SMD -0.19, 95% CI -0.35, -0.33). No significant differences in DAE were detected between bDMARDs. In conclusion, anti-tumor necrosis factor agents (adalimumab, infliximab, and etanercept) may be preferred for treating psoriatic arthritis for their superiority in preventing radiographic progression.
PubMed: 36297574
DOI: 10.3390/pharmaceutics14102140 -
The Cochrane Database of Systematic... Nov 2014Most people who receive a kidney transplant die from either cardiovascular disease or cancer before their transplant fails. The most common reason for someone with a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Most people who receive a kidney transplant die from either cardiovascular disease or cancer before their transplant fails. The most common reason for someone with a kidney transplant to lose the function of their transplanted kidney necessitating return to dialysis is chronic kidney transplant scarring. Immunosuppressant drugs have side effects that increase risks of cardiovascular disease, cancer and chronic kidney transplant scarring. Belatacept may provide sufficient immunosuppression while avoiding unwanted side effects of other immunosuppressant drugs. However, high rates of post-transplant lymphoproliferative disease (PTLD) have been reported when belatacept is used in particular kidney transplant recipients at high dosage.
OBJECTIVES
1) Compare the relative efficacy of belatacept versus any other primary immunosuppression regimen for preventing acute rejection, maintaining kidney transplant function, and preventing death. 2) Compare the incidence of several adverse events: PTLD; other malignancies; chronic transplant kidney scarring (IF/TA); infections; change in blood pressure, lipid and blood sugar control. 3) Assess any variation in effects by study, intervention and recipient characteristics, including: differences in pre-transplant Epstein Barr virus serostatus; belatacept dosage; and donor-category (living, standard criteria deceased, or extended criteria deceased).
SEARCH METHODS
We searched the Cochrane Renal Group's Specialised Register to 1 September 2014 through contact with the Trials' Search Co-ordinator using search terms relevant to this review.
SELECTION CRITERIA
Randomised controlled trials (RCT) that compared belatacept versus any other immunosuppression regimen in kidney transplant recipients were eligible for inclusion.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data for study quality and transplant outcomes and synthesized results using random effects meta-analysis, expressed as risk ratios (RR) and mean differences (MD), both with 95% confidence intervals (CI). Subgroup analyses and univariate meta-regression were used to investigate potential heterogeneity.
MAIN RESULTS
We included five studies that compared belatacept and calcineurin inhibitors (CNI) that reported data from a total of 1535 kidney transplant recipients. Of the five studies, three (478 participants) compared belatacept and cyclosporin and two (43 recipients) compared belatacept and tacrolimus. Co-interventions included basiliximab (4 studies, 1434 recipients); anti-thymocyte globulin (1 study, 89 recipients); alemtuzumab (1 study, 12 recipients); mycophenolate mofetil (MMF, 5 studies, 1509 recipients); sirolimus (1 study, 26 recipients) and prednisone (5 studies, 1535 recipients).Up to three years following transplant, belatacept and CNI-treated recipients were at similar risk of dying (4 studies, 1516 recipients: RR 0.75, 95% CI 0.39 to 1.44), losing their kidney transplant and returning to dialysis (4 studies, 1516 recipients: RR 0.91, 95% CI 0.61 to 1.38), and having an episode of acute rejection (4 studies, 1516 recipients: RR 1.56, 95% CI 0.85 to 2.86). Belatacept-treated kidney transplant recipients were 28% less likely to have chronic kidney scarring (3 studies, 1360 recipients: RR 0.72, 95% CI 0.55 to 0.94) and also had better graft function (measured glomerular filtration rate (GFR) (3 studies 1083 recipients): 10.89 mL/min/1.73 m², 95% CI 4.01 to 17.77; estimated GFR (4 studies, 1083 recipients): MD 9.96 mL/min/1.73 m², 95% CI 3.28 to 16.64) than CNI-treated recipients. Blood pressure was lower (systolic (2 studies, 658 recipients): MD -7.51 mm Hg, 95% CI -10.57 to -4.46; diastolic (2 studies, 658 recipients): MD -3.07 mm Hg, 95% CI -4.83 to -1.31, lipid profile was better (non-HDL (3 studies 1101 recipients): MD -12.25 mg/dL, 95% CI -17.93 to -6.57; triglycerides (3 studies 1101 recipients): MD -24.09 mg/dL, 95% CI -44.55 to -3.64), and incidence of new-onset diabetes after transplant was reduced by 39% (4 studies (1049 recipients): RR 0.61, 95% CI 0.40 to 0.93) among belatacept-treated versus CNI-treated recipients.Risk of PTLD was similar in belatacept and CNI-treated recipients (4 studies, 1516 recipients: RR 2.79, 95% CI 0.61 to 12.66) and was no different among recipients who received different belatacept dosages (high versus low dosage: ratio of risk ratios (RRR) 1.06, 95% CI 0.11 to 9.80, test of difference = 0.96) or among those who were Epstein Barr virus seronegative compared with those who were seropositive before their kidney transplant (seronegative versus seropositive; RRR 1.49, 95% CI 0.15 to 14.76, test for difference = 0.73).The belatacept dose used (high versus low), type of donor kidney the recipient received (extended versus standard criteria) and whether the kidney transplant recipient received tacrolimus or cyclosporin made no difference to kidney transplant survival, incidence of acute rejection or estimated GFR. Selective outcome reporting meant that data for some key subgroup comparisons were sparse and that estimates of the effect of treatment in these groups of recipients remain imprecise.
AUTHORS' CONCLUSIONS
There is no evidence of any difference in the effectiveness of belatacept and CNI in preventing acute rejection, graft loss and death, but treatment with belatacept is associated with less chronic kidney scarring and better kidney transplant function. Treatment with belatacept is also associated with better blood pressure and lipid profile and a lower incidence of diabetes versus treatment with a CNI. Important side effects (particularly PTLD) remain poorly reported and so the relative benefits and harms of using belatacept remain unclear. Whether short-term advantages of treatment with belatacept are maintained over the medium- to long-term or translate into better cardiovascular outcomes or longer kidney transplant survival with function remains unclear. Longer-term, fully reported and published studies comparing belatacept versus tacrolimus are needed to help clinicians decide which patients might benefit most from using belatacept.
Topics: Abatacept; Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antilymphocyte Serum; Basiliximab; Calcineurin Inhibitors; Cyclosporine; Graft Rejection; Graft Survival; Humans; Immunoconjugates; Immunosuppressive Agents; Kidney Transplantation; Lymphoproliferative Disorders; Mycophenolic Acid; Prednisone; Randomized Controlled Trials as Topic; Recombinant Fusion Proteins; Sirolimus; Tacrolimus
PubMed: 25416857
DOI: 10.1002/14651858.CD010699.pub2 -
European Review For Medical and... Apr 2021Rheumatoid arthritis is a chronic autoimmune disease. Treatment aims to reduce and improve its signs and symptoms. Hence, Disease-Modifying Antirheumatic Drugs (DMARDs)...
OBJECTIVE
Rheumatoid arthritis is a chronic autoimmune disease. Treatment aims to reduce and improve its signs and symptoms. Hence, Disease-Modifying Antirheumatic Drugs (DMARDs) are the treatment of choice. The objective of this study was to identify potential interactions between DMARDs and the drugs most frequently prescribed in dentistry in order to avoid adverse reactions.
MATERIALS AND METHODS
This literature review sets out to define possible adverse reactions provoked by pharmacological interactions between DMARDs and the drugs commonly prescribed in dentistry. A search was conducted in PubMed by searching the names of drugs used in dentistry, "drug interactions," "rheumatoid arthritis," and "dentistry", "hydroxychloroquine", "leflunomide", "methotrexate", "sulfasalazine", "adalimumab", "anakinra", "etanercept", "abatacept", "infliximab" and "rituximab".
RESULTS
It was found that most DMARDs show potential interactions with many drugs used in dentistry, including various antibiotics, analgesics, anesthetics, antifungals, and corticosteroids.
CONCLUSIONS
It is clinically important for oral health clinicians to be aware of possible drug interactions between DMARDs and the drugs commonly prescribed in dentistry to prevent potential adverse reactions and avoid endangering the patient.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Drug Interactions; Humans
PubMed: 33877648
DOI: 10.26355/eurrev_202104_25536 -
Clinical and Experimental Rheumatology 2020This systematic literature review (SLR) and network meta-analysis (NMA) was aimed at comparing the relative efficacy and safety of abatacept (ABA) with other currently... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
This systematic literature review (SLR) and network meta-analysis (NMA) was aimed at comparing the relative efficacy and safety of abatacept (ABA) with other currently recommended therapies for patients with early RA.
METHODS
An SLR (January 1998 to June 2018) was conducted including MEDLINE®, Embase, and CENTRAL databases, and grey literature. Population was adults with active RA for ≤2 years treated with biologic DMARDs as monotherapy or in combination with conventional DMARDs. A Bayesian NMA was performed using randomised controlled trials (RCTs) and comparisons for ACR50, DAS28 remission, withdrawal due to adverse events and total withdrawal where reported.
RESULTS
Ninety publications pertaining to 69 studies (43 RCTs and 26 observational studies) were identified. Twenty-eight RCTs were eligible to be included in the NMA. ABA as monotherapy was similar to the combination of ABA+methotrexate (MTX) for ACR50 (RR: 0.82 [95% CI 0.51-1.35]), and DAS28 remission (RR: 0.69 [95% CI 0.37-1.3]), as well as for withdrawal due to AEs (RR: 2.35 [95% CI 0.69-7.38]) and all-cause withdrawal (RR: 1.73 [95% CI 0.905-3.35]). ABA as monotherapy and ABA+MTX were both comparable to all other therapies for the main efficacy and safety outcomes. Observational study data reported was congruous with the RCT analysis.
CONCLUSIONS
The results of this NMA show similar efficacy and safety between ABA (as monotherapy or in combination with MTX) and other biologics in early RA. Further comparison of different treatment options for early RA is warranted as growing research provides evidence for the application of new novel therapies for RA.
Topics: Abatacept; Adult; Antirheumatic Agents; Arthritis, Rheumatoid; Biological Products; Drug Therapy, Combination; Humans; Methotrexate; Network Meta-Analysis
PubMed: 32301430
DOI: No ID Found -
Psoriasis (Auckland, N.Z.) 2015Psoriatic arthritis is an inflammatory arthritis the primary manifestations of which are locomotor and skin disease. Although a number of guidelines have been published... (Review)
Review
BACKGROUND
Psoriatic arthritis is an inflammatory arthritis the primary manifestations of which are locomotor and skin disease. Although a number of guidelines have been published citing strategies for reducing disease progression, the evidence base for disease-modifying agents is unclear. This forms the focus of this systematic review.
METHODS
The systematic review was undertaken according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009 checklist. We selected randomized controlled trials (RCTs) that looked at the impact of interventions with disease-modifying agents, either synthetic drugs or biologics on musculoskeletal outcomes, notably American College of Rheumatology 20 percent responders. Results were analyzed using Review Manager 5.1.6 (Cochrane Collaboration, Oxford, UK). Whilst our primary focus was on published trials, we also looked at new trials presented in abstract form in 2013-2014 that were not yet published to avoid omitting important and up-to-date information on developing treatments.
RESULTS
Our in-depth analysis included 28 trials overall enrolling 5,177 patients published between the 1980s and now as well as limited analysis of some studies in abstract form as described earlier. The most frequently available locomotor outcome measure was the American College of Rheumatology 20 percent responders. The risk ratio for achieving an American College of Rheumatology 20 percent responders response was positive in favor of treatment (risk ratio 2.30; 95% confidence interval 1.78-2.96); however, there was evidence of considerable heterogeneity between trials. Overall randomized controlled trials of established synthetic disease-modifying agents were largely negative (methotrexate, ciclosporin and sulfasalazine) though leflunomide showed a small positive effect. A new synthetic agent, apremilast, did show a positive benefit. For biologics, TNF inhibitors already licensed for use were effective and similar benefits were seen with newer agents including ustekinumab, secukinumab, brodalumab, and abatacept, although the latter did not impact on skin problems. Important limitations of the systematic review included, first, the fact that for many agents there were little data and, second, much of the recent data for newer biologics were only available in abstract form.
CONCLUSION
Conventional disease-modifying agents, with the possible exception of leflunomide, do not show clear evidence of disease-modifying effects in psoriatic arthritis, though a newer synthetic disease-modifying agents, apremilast, appears more effective. Biologic agents appear more beneficial, although more evidence is required for newer agents. This review suggests that it may be necessary to review existing national and international management guidelines for psoriatic arthritis.
PubMed: 29387584
DOI: 10.2147/PTT.S52893 -
Clinical and Experimental Rheumatology 2020There is no hierarchy in the use of biotherapies (bDMARDs) in psoriatic arthritis (PsA) and no published head-to-head comparative studies. Our purpose is to evaluate the... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
There is no hierarchy in the use of biotherapies (bDMARDs) in psoriatic arthritis (PsA) and no published head-to-head comparative studies. Our purpose is to evaluate the respective efficacy of TNF inhibitors, IL12/23 inhibitors (ustekinumab), IL17 inhibitors (secukinumab, ixekizumab) and CTLA4Ig (abatacept) on articular, enthesitis, dactylitis, skin and functional outcomes in PsA.
METHODS
Randomised controlled trials assessing bDMARDs in PsA were selected through the MedLine, Cochrane and Embase databases. ACR20/50/70 and PASI75/90 response rates, enthesitis and dactylitis reduction rates and HAQ-DI mean reductions were collected. Pooled meta-analyses were performed to assess relative risks (RR) with their 95% confidence interval (95%CI) for each class of bDMARDs in comparison with placebo.
RESULTS
17 RCTs were analysed. Compared to placebo, all bDMARDs showed higher ACR20 response rates, with RRs ranging from 1.77 (1.31, 2.39) to 3.21 (2.52, 4.08), and a greater HAQ-DI mean reduction. TNF inhibitors, secukinumab and IL17 inhibitors showed higher ACR50/70 and PASI75/90 response rates. TNF inhibitors, secukinumab and IL17 inhibitors showed higher enthesitis resolution rates and only TNF inhibitors and IL17 inhibitors showed higher dactylitis resolution rates, with RRs ranging from 1.41 (1.02, 1.95) to 2.31 (1.60, 3.34) and from 2.07 (1.38, 3.12) to 2.65 (1.79, 3.94), respectively.
CONCLUSIONS
All bDMARDs showed higher ACR20 response rates and better HAQ-DI mean reduction compared to placebo. This meta-analysis highlights the variability of bDMARD efficacy on ACR50/70, PASI75/90 and enthesitis or dactylitis response rates. Head-to-head studies are needed to draw definitive conclusions on potential efficacy-related differences between bDMARDs in PsA.
Topics: Abatacept; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Arthritis, Psoriatic; Enthesopathy; Humans; Randomized Controlled Trials as Topic; Treatment Outcome; Ustekinumab
PubMed: 31969228
DOI: No ID Found