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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 -
Clinical Nephrology Sep 2020The efficacy of abatacept has been demonstrated mainly in case reports, case series, and observational studies with small sample size. With current evidence, it is...
Efficacy of abatacept treatment for focal segmental glomerulosclerosis and minimal change disease: A systematic review of case reports, case series, and observational studies .
INTRODUCTION
The efficacy of abatacept has been demonstrated mainly in case reports, case series, and observational studies with small sample size. With current evidence, it is premature to conclude that abatacept is an effective treatment for nephrotic syndrome.
MATERIALS AND METHODS
We searched MEDLINE, SCOPUS, and Cochrane Library until December 2019 for studies including patients with focal segmental glomerulosclerosis (FSGS) or minimal change disease (MCD) treated with abatacept. Proteinuria recovery and remission were outcomes of interest. Presence of urinary CD80 level of B7-1 staining on kidney biopsies was also reported.
RESULTS
A total of 11 studies (n = 32) were included in the systematic review. 60% of patients were male. The median age was 27.5 years (range 5.2 - 72 years). Approximately 90.6% had FSGS, while 9.4% had MCD. With median follow-up of 12 months (IQR 6.38), only 15 patients (46.9%) showed response in proteinuria reduction, and 12 patients (43.8%) achieved remission with abatacept. Serious adverse events were reported in 12.5%. Additionally, we observed that patients with positive B7-1 staining on kidney biopsies had higher odds of achieving remission with abatacept (likelihood ratio 18.25; p < 0.001). We found no significant correlation between elevated CD80 levels and remissions.
CONCLUSION
The efficacy of abatacept therapy for FSGS or MCD was only 43.8%. Serious adverse effects are common. However, our study suggested that abatacept should be considered only in patients with positive B7-1 staining on kidney biopsy because these patients tend to respond to treatment.
Topics: Abatacept; Adolescent; Adult; Aged; B7-1 Antigen; Biopsy; Child; Child, Preschool; Female; Glomerulosclerosis, Focal Segmental; Humans; Kidney; Male; Middle Aged; Nephrosis, Lipoid; Young Adult
PubMed: 32589135
DOI: 10.5414/CN110134 -
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 -
The Journal of Rheumatology Jan 2023To determine the risk of not being able to sustain remission after tapering methotrexate (MTX) from targeted therapy in patients with controlled rheumatoid arthritis... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To determine the risk of not being able to sustain remission after tapering methotrexate (MTX) from targeted therapy in patients with controlled rheumatoid arthritis (RA).
METHODS
A systematic literature search was conducted in MEDLINE, Embase, and the Cochrane Library for studies reporting remission outcomes after tapering MTX from targeted therapies in RA. Full-text articles and abstracts reported in English were included. Metaanalyses were conducted using random-effects models. Forest and funnel plots were created.
RESULTS
A total of 10 articles were included. Studies evaluated MTX being tapered from combination treatment with tumor necrosis factor inhibitors, tocilizumab, abatacept, and tofacitinib. A total of 9 studies used a randomized design and 1 was observational. Out of 10 studies, 3 focused on early RA (ie, < 1 yr). The MTX-tapering strategy was gradual in 2 studies and rapid in 8 studies. Follow-up ranged from 3 to 18 months in randomized trials and up to 3 years in the observational study. Our metaanalysis, which included 2000 participants with RA from 10 studies, showed that patients who tapered MTX from targeted therapy had a 10% reduction in the ability to sustain remission and an overall pooled risk ratio of 0.90 (95% CI 0.84-0.97). There was no heterogeneity ( = 0%, = 0.94). Our funnel plot indicated minimal publication bias.
CONCLUSION
Patients with controlled RA may taper MTX from targeted therapy with a 10% reduction in the ability to sustain remission for up to 18 months. Longer follow-up studies with attention to radiographic, functional, and patient-reported outcomes are needed. The risk of disease worsening should be discussed with the patient with careful follow-up and prompt retreatment of disease worsening.
Topics: Humans; Methotrexate; Antirheumatic Agents; Arthritis, Rheumatoid; Abatacept; Tumor Necrosis Factor Inhibitors; Drug Therapy, Combination; Treatment Outcome; Observational Studies as Topic
PubMed: 35970524
DOI: 10.3899/jrheum.220152 -
Autoimmunity Reviews Jan 2022The treatment for COVID-19 often utilizes immune-modulating drugs. These drugs are also used in immune mediated inflammatory diseases (IMIDs). We performed a systematic... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The treatment for COVID-19 often utilizes immune-modulating drugs. These drugs are also used in immune mediated inflammatory diseases (IMIDs). We performed a systematic review about seroconversion after SARS-CoV-2 vaccination in patients with IMIDs and impact of various drugs on seroconversion rates.
METHODS
Electronic databases were searched to identify relevant studies reporting seroconversion rates following SARS-CoV-2 vaccination in IMIDs. We calculated the pooled seroconversion rates after a single or two doses of vaccination, pooled seroconversion rates in patients with specific IMIDs, and rates in patients on various drugs/drug classes.
RESULTS
Twenty-five studies were included in the systematic review. The pooled seroconversion rates after two doses of mRNA vaccination were higher (83.1, 95%CI: 74.9-89.0, I = 90%) as compared to a single dose (69.3, 52.4-82.3, I = 95%). The odds of seroconversion were lower in IMIDs as compared to healthy controls (0.05, 0.02-0.13, I = 21%). The seroconversion rates in patients with inflammatory bowel disease (95.2, 95%CI: 92.6-96.9, I = 0%), spondyloarthropathy (95.6, 95% CI: 83.4-98.9, I = 35%), and systemic lupus erythematosus (90.7, 95%CI: 85.4-94.2, I = 0%) were higher as compared to rheumatoid arthritis (79.5, 95% CI: 65.1-88.9, I = 85%), and vasculitis (70.5, 95% CI: 52.9-83.5, I = 51%). The seroconversion rates following double dose of mRNA were excellent (>90%) in those on anti-tumour necrosis factor (TNF), anti-integrin (vedolizumab), anti-IL 17 (secukinumab), anti-IL6 (Tocilizumab) and anti-IL12/23 (Ustekinumab) therapies but attenuated (<70%) in patients on anti-CD20 (Rituximab) or anti-cytotoxic T lymphocyte associated antigen (CTLA-4) therapies (Abatacept). The seroconversion rates were good (70-90%) with steroids, hydroxychloroquine, JAK inhibitors, mycophenolate mofetil and leflunomide. Combination of anti-TNF with immunomodulators (azathioprine, 6-meracptopurine, methotrexate) resulted in an attenuated vaccine response as compared to anti-TNF monotherapy.
CONCLUSION
Seroconversion rates after SARS-CoV-2 vaccination are lower in patients with IMIDs. Certain therapies (anti-TNF, anti-integrin, anti-IL 17, anti-IL6, anti-12/23) do not impact seroconversion rates while others (anti-CD20, anti-CTLA-4) result in poorer responses.
Topics: COVID-19; COVID-19 Vaccines; Humans; SARS-CoV-2; Tumor Necrosis Factor Inhibitors; Vaccination
PubMed: 34474172
DOI: 10.1016/j.autrev.2021.102927 -
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 -
The Journal of Rheumatology Jan 2020Understanding the placebo response is critical to interpreting treatment efficacy, particularly for agents with a ceiling to their therapeutic effect, where an...
OBJECTIVE
Understanding the placebo response is critical to interpreting treatment efficacy, particularly for agents with a ceiling to their therapeutic effect, where an increasing placebo response makes it harder to detect potential benefit. The objective of this study is to assess the change in placebo responses over time in rheumatoid arthritis (RA) randomized placebo-controlled trials (RCT) for drug licensing authorization.
METHODS
The Cochrane Controlled Trials Register database was searched to identify RCT of biological or targeted synthetic disease-modifying antirheumatic drugs (DMARD) in RA. Studies were excluded if patients were conventional synthetic DMARD (csDMARD)-naive, not receiving background csDMARD therapy, or were biologic experienced. Metaregression model was used to evaluate changes in American College of Rheumatology (ACR) 20, ACR50, and ACR70 treatment response over time.
RESULTS
There were 32 trials in total: anti-tumor necrosis factor therapy (n = 15), tocilizumab (n = 4), abatacept (n = 2), rituximab (n = 2), and Janus kinase inhibitors (n = 9). From 1999 to 2018, there was no significant trend in the age or sex of patients in the placebo arm. Disease duration, swollen joint count, and 28-joint count Disease Activity Score using erythrocyte sedimentation rate at baseline all significantly declined over time. There was a statistically significant increase in placebo ACR50 and ACR70 responses (ACR50 β = 0.41, 95% CI 0.09-0.74, p = 0.01; ACR70 β = 0.18, 95% CI 0.04-0.31, p = 0.01) that remained significant after controlling for potential confounders.
CONCLUSION
There has been a rise in the placebo response in RA clinical trials over the last 2 decades. Shifting RA phenotype, changes in trial design, and expectation bias are possible explanations for this phenomenon. This observation has important implications when evaluating newer novel agents against established therapies.
Topics: Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Arthritis, Rheumatoid; Biological Products; Female; Humans; Janus Kinase Inhibitors; Male; Middle Aged; Patient Outcome Assessment; Placebo Effect; Randomized Controlled Trials as Topic; Treatment Outcome; Tumor Necrosis Factor Inhibitors; Tumor Necrosis Factor-alpha
PubMed: 31043548
DOI: 10.3899/jrheum.190008 -
Clinical Rheumatology Nov 2021The pharmacotherapy of Takayasu arteritis (TAK) with disease-modifying anti-rheumatic drugs (DMARDs) is an evolving area. A systematic review of Scopus, Web of Science,... (Meta-Analysis)
Meta-Analysis Review
The pharmacotherapy of Takayasu arteritis (TAK) with disease-modifying anti-rheumatic drugs (DMARDs) is an evolving area. A systematic review of Scopus, Web of Science, Pubmed Central, clinical trial databases and recent international rheumatology conferences for interventional and observational studies reporting the effectiveness of DMARDs in TAK identified four randomized controlled trials (RCTs, with another longer-term follow-up of one RCT) and 63 observational studies. The identified trials had some concern or high risk of bias. Most observational studies were downgraded on the Newcastle-Ottawa scale due to lack of appropriate comparator groups. Studies used heterogenous outcomes of clinical responses, angiographic stabilization, normalization of inflammatory markers, reduction in vascular uptake on positron emission tomography, reduction in prednisolone doses and relapses. Tocilizumab showed benefit in a RCT compared to placebo in a secondary per-protocol analysis but not the primary intention-to-treat analysis. Abatacept failed to demonstrate benefit compared to placebo for preventing relapses in another RCT. Pooled data from uncontrolled observational studies demonstrated beneficial clinical responses and angiographic stabilization in nearly 80% patients treated with tumour necrosis factor alpha inhibitors, tocilizumab or leflunomide. Certainty of evidence for outcomes from RCTs ranged from moderate to very low and was low to very low for all observational studies. There is a paucity of high-quality evidence to guide the pharmacotherapy of TAK. Future observational studies should attempt to include appropriate comparator arms. Multicentric, adequately powered RCTs assessing both clinical and angiographic responses are necessary in TAK.
Topics: Abatacept; Antibodies, Monoclonal; Antirheumatic Agents; Humans; Neoplasm Recurrence, Local; Randomized Controlled Trials as Topic; Takayasu Arteritis
PubMed: 33932173
DOI: 10.1007/s10067-021-05743-2 -
Journal of Clinical Medicine Sep 2021Scleroderma (morphea) en coup de sabre is a localized subtype restricted to the frontoparietal region of the head. Current treatment paradigms rely on low levels of... (Review)
Review
Scleroderma (morphea) en coup de sabre is a localized subtype restricted to the frontoparietal region of the head. Current treatment paradigms rely on low levels of evidence, primarily case reports and case series-supported by expert opinions. The aim of this article was to systematically analyze current data related to the treatment of localized scleroderma en coup de sabre. The databases Scopus, PubMed, and EBSCO were searched for all reports discussing the treatment of localized scleroderma en coup de sabre. The keywords en coup de sabre, "facial linear scleroderma", and "morphea linearis", combined with "treatment" or "therapy" were used as search terms. A total of 34 articles analyzed treatment outcomes for patients with localized scleroderma en coup de sabre including 4 retrospective cohort studies, 2 prospective cohort studies, 4 case series, and 24 case reports, representing a total of 69 patients (38 children and 31 adults). Methotrexate was the most commonly investigated treatment (26 patients) with a highest response rate (26/26, 100%). Other treatments included systemic glucocorticosteroids (nine patients), followed by UVA1 (four patients), mycophenolate mofetil (two patients), hydroxychloroquine (five patients), abatacept (two patients), tocilizumab (three patients), cyclosporine (one patient), interferon gamma (one patient), PUVA therapy (two patients), NB-UVB therapy (one patient), and pulsed dye laser (one patient). Reconstructive and surgery treatment was successfully used for lesions with settled disease activity to improve the cosmetic aspect of the lesions. Conclusion: methotrexate is the most often-studied treatment and reported good clinical outcomes in children and adults with localized scleroderma en coup de sabre.
PubMed: 34640533
DOI: 10.3390/jcm10194517