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Skin Appendage Disorders Jan 2020Hair graying is a common sign of aging resulting from complex regulation of melanogenesis. Currently, there is no medical treatment available for hair repigmentation. In... (Review)
Review
Hair graying is a common sign of aging resulting from complex regulation of melanogenesis. Currently, there is no medical treatment available for hair repigmentation. In this article we review the literature on medication-induced hair repigmentation, discuss the potential mechanisms of action, and review the quality of the literary data. To date, there have been 27 studies discussing medication-induced gray hair repigmentation, including 6 articles on gray hair repigmentation as a primary objective, notably with psoralen treatment or vitamin supplementation, and 21 reports on medication-induced gray hair repigmentation as an incidental finding. Medications noted in the literature include anti-inflammatory medications (thalidomide, lenalidomide, adalimumab, acitretin, etretinate, prednisone, cyclosporin, cisplatinum, interferon-α, and psoralen), stimulators of melanogenesis (latanoprost, erlotinib, imatinib, tamoxifen, and levodopa), vitamins (calcium pantothenate and -amino benzoic acid), a medication that accumulates in tissues (clofazimine), and a medication with an undetermined mechanism (captopril). Diffuse repigmentation of gray hair can be induced by certain medications that inhibit inflammation or stimulate melanogenesis. There is also low-quality evidence that some vitamin B complex supplementation can promote gray hair darkening. While these compounds are not currently indicated for the treatment of gray hair, their mechanisms shed light on targets for future medications for hair repigmentation.
PubMed: 32021854
DOI: 10.1159/000504414 -
The Cochrane Database of Systematic... Feb 2022Focal segmental glomerulosclerosis (FSGS) can be separated into primary, genetic or secondary causes. Primary disease results in nephrotic syndrome while genetic and... (Review)
Review
BACKGROUND
Focal segmental glomerulosclerosis (FSGS) can be separated into primary, genetic or secondary causes. Primary disease results in nephrotic syndrome while genetic and secondary forms may be associated with asymptomatic proteinuria or with nephrotic syndrome. Overall only about 20% of patients with FSGS experience a partial or complete remission of nephrotic syndrome with treatment. FSGS progresses to kidney failure in about half of the cases. This is an update of a review first published in 2008.
OBJECTIVES
To assess the benefits and harms of immunosuppressive and non-immunosuppressive treatment regimens in adults with FSGS.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies to 21 June 2021 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
Randomised controlled trials (RCTs) and quasi-RCTs of any intervention for FSGS in adults were included. Studies comparing different types, routes, frequencies, and duration of immunosuppressive agents and non-immunosuppressive agents were assessed.
DATA COLLECTION AND ANALYSIS
At least two authors independently assessed study quality and extracted data. Statistical analyses were performed using the random-effects model and results were expressed as a risk ratio (RR) for dichotomous outcomes, or mean difference (MD) for continuous data with 95% confidence intervals (CI). Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
MAIN RESULTS
Fifteen studies (560 participants) were included. No studies specifically evaluating corticosteroids compared with placebo or supportive therapy were identified. Studies evaluated participants with steroid-resistant FSGS. Five studies (240 participants) compared cyclosporin with or without prednisone with different comparators (no specific treatment, prednisone, methylprednisolone, mycophenolate mofetil (MMF), dexamethasone). Three small studies compared monoclonal antibodies (adalimumab, fresolimumab) with other agents or placebo. Six single small studies compared rituximab with tacrolimus, cyclosporin plus valsartan with cyclosporin alone, MMF with prednisone, chlorambucil plus methylprednisolone and prednisone with no specific treatment, different regimens of dexamethasone and CCX140-B (an antagonist of the chemokine receptor CCR2) with placebo. The final study (109 participants) compared sparsentan, a dual inhibitor of endothelin Type A receptor and of the angiotensin II Type 1 receptor, with irbesartan. In the risk of bias assessment, seven and five studies were at low risk of bias for sequence generation and allocation concealment, respectively. Four studies were at low risk of performance bias and 14 studies were at low risk of detection bias. Thirteen, six and five studies were at low risk of attrition bias, reporting bias and other bias, respectively. Of five studies evaluating cyclosporin, four could be included in our meta-analyses (231 participants). Cyclosporin with or without prednisone compared with different comparators may increase the likelihood of complete remission (RR 2.31, 95% CI 1.13 to 4.73; I² = 1%; low certainty evidence) and of complete or partial remission (RR 1.64, 95% CI 1.10 to 2.44; I² = 19%) but not of partial remission (RR 1.36, 95% CI 0.78 to 2.39, I² = 22%). In Individual studies, cyclosporin with prednisone versus prednisone may increase the likelihood of partial (49 participants: RR 7.96, 95% CI 1.09 to 58.15) or complete or partial remission (49 participants: RR 8.85, 95% CI 1.22 to 63.92) but not of complete remission. The remaining individual comparisons may make little or no difference to the likelihood of complete remission, partial remission or complete or partial remission compared with no treatment, methylprednisolone, MMF, or dexamethasone. Individual study data and combined data showed that cyclosporin may make little or no difference to the outcomes of chronic kidney disease or kidney failure. It is uncertain whether cyclosporin compared with these comparators in individual or combined analyses makes any difference to the outcomes of hypertension or infection. MMF compared with prednisone may make little or no difference to the likelihood of complete remission (33 participants: RR 1.05, 95% CI 0.58 to 1.88; low certainty evidence), partial remission, complete or partial remission, glomerular filtration rate, or infection. It is uncertain whether other interventions make any difference to outcomes as the certainty of the evidence is very low. It is uncertain whether sparsentan reduces proteinuria to a greater extent than irbesartan.
AUTHORS' CONCLUSIONS
No RCTs, which evaluated corticosteroids, were identified although the KDIGO guidelines recommend corticosteroids as the first treatment for adults with FSGS. The studies identified included participants with steroid-resistant FSGS. Treatment with cyclosporin for at least six months was more likely to achieve complete remission of proteinuria compared with other treatments but there was considerable imprecision due to few studies and small participant numbers. In future studies of existing or new interventions, the investigators must clearly define the populations included in the study to provide appropriate recommendations for patients with primary, genetic or secondary FSGS.
Topics: Adult; Cyclosporine; Glomerulosclerosis, Focal Segmental; Humans; Immunosuppressive Agents; Mycophenolic Acid; Prednisone; Randomized Controlled Trials as Topic
PubMed: 35224732
DOI: 10.1002/14651858.CD003233.pub3 -
Clinical Kidney Journal Apr 2021The efficacy and safety of rituximab (RTX) in adult frequent-relapsing (FR) or steroid-dependent (SD) nephrotic syndrome (NS), including minimal change disease (MCD) or... (Review)
Review
Efficacy and safety of rituximab in adult frequent-relapsing or steroid-dependent minimal change disease or focal segmental glomerulosclerosis: a systematic review and meta-analysis.
BACKGROUND
The efficacy and safety of rituximab (RTX) in adult frequent-relapsing (FR) or steroid-dependent (SD) nephrotic syndrome (NS), including minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS), are still inconclusive.
METHODS
We performed a systematic review and meta-analysis registered in PROSPERO (CRD42019148102) by pooling data of cohort studies or case series on adult patients with difficult-to-treat NS. Steroid-resistant NS was excluded. The primary outcomes were the complete remission (CR) rate and the relapse rate. Partial remission (PR) rate, no response (NR) rate and adverse events were the secondary outcomes. A random-effects model was performed for all the outcomes.
RESULTS
We included 21 studies involving 382 adult MCD/FSGS subjects with a median follow-up duration from 12 to 43 months. RTX treatment induced a pooled 84.2% CR rate [95% confidence interval (CI): 67.7-96.3%], while MCD patients had a high 91.6% CR rate and FSGS patients a moderate 43% CR rate. However, 27.4% (95% CI 20.7-34.5%) of the patients relapsed during the follow-up. The pooled PR and NR rates were 5.8% (95% CI 1.2-12.5%) and 5.2% (95% CI 0.0-15.0%), respectively. RTX was associated with trivial adverse events and good tolerance.
CONCLUSIONS
In summary, by pooling results of current pilot studies, RTX may be an effective and relatively safe alternative for most adult FR or SD MCD/FSGS to displace calcineurin inhibitors or prednisone in the hierarchy of treatment. More clinical trials comparing RTX with other immunosuppressants and concerning the long-term adverse events are needed.
PubMed: 34094516
DOI: 10.1093/ckj/sfaa191 -
Cancer Science Jul 2021Chemotherapy for non-Hodgkin lymphoma (NHL) in the hemodialysis (HD) patient is a challenging situation. Because many drugs are predominantly eliminated by the kidneys,...
Chemotherapy for non-Hodgkin lymphoma (NHL) in the hemodialysis (HD) patient is a challenging situation. Because many drugs are predominantly eliminated by the kidneys, chemotherapy in the HD patient requires special considerations concerning dose adjustments to avoid overdose and toxicities. Conversely, some drugs are removed by HD and may expose the patient to undertreatment, therefore the timing of drug administration in relation to HD sessions must be carefully planned. Also, the metabolites of some drugs show different toxicities and dialysability as compared with the parent drug, therefore this must also be catered for. However, the pharmacokinetics of many chemotherapeutics and their metabolites in HD patients are unknown, and the fact that NHL patients are often treated with distinct multiagent chemotherapy regimens makes the situation more complicated. In a realm where uncertainty prevails, case reports and case series reporting on actual treatment and outcomes are extremely valuable and can aid physicians in decision making from drug selection to dosing. We carried out an exhaustive review of the literature and adopted 48 manuscripts consisting of 66 HD patients undergoing 71 chemotherapy regimens for NHL, summarized the data, and provide recommendations concerning dose adjustments and timing of administration for individual chemotherapeutics where possible. The chemotherapy regimens studied in this review include, but are not limited to, rituximab, cyclophosphamide + vincristine + prednisolone (CVP) and cyclophosphamide + doxorubicin + vincristine + prednisolone (CHOP)-like regimens, chlorambucil, ibrutinib, bendamustine, methotrexate, platinum compounds, cytarabine, gemcitabine, etoposide, ifosfamide, melphalan, busulfan, fludarabine, mogamulizumab, brentuximab vedotin, and Y-ibritumomab tiuxetan.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Child; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Female; Hematopoietic Stem Cell Transplantation; Humans; Kidney; Lymphoma, Non-Hodgkin; Male; Middle Aged; Prednisone; Renal Dialysis; Rituximab; Vincristine; Young Adult
PubMed: 33938097
DOI: 10.1111/cas.14933 -
Advances in Therapy May 2022Many treatment regimens have been evaluated in transplant-ineligible (TIE) patients with newly diagnosed multiple myeloma (NDMM). The objective of this study was to... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Many treatment regimens have been evaluated in transplant-ineligible (TIE) patients with newly diagnosed multiple myeloma (NDMM). The objective of this study was to compare the efficacy of relevant therapies for the treatment of TIE patients with NDMM.
METHODS
Progression-free survival (PFS) and overall survival (OS) from large randomised controlled trials (RCTs) evaluating different treatment options for TIE patients with NDMM were compared in a network meta-analysis (NMA). The NMA includes recent primary and long-term OS readouts from SWOG S0777, ENDURANCE, MAIA, and ALCYONE. Relevant trials were identified through a systematic literature review. Relative efficacy measures (i.e., hazard ratios [HRs] for PFS and OS) were extracted and synthesised in random-effects NMAs.
RESULTS
A total of 122 publications describing 45 unique RCTs was identified. Continuous lenalidomide/dexamethasone (Rd) was selected as the referent comparator. Daratumumab-containing treatments (daratumumab/lenalidomide/dexamethasone [D-Rd], daratumumab/bortezomib/melphalan/prednisone [D-VMP]) and bortezomib/lenalidomide/dexamethasone (VRd) had the highest probabilities of being more effective than Rd continuous for PFS (HR: D-Rd, 0.53; D-VMP, 0.57, VRd, 0.77) and OS (HR: D-Rd, 0.68; VRd, 0.77, D-VMP, 0.78). D-Rd had the highest chance of being ranked as the most effective treatment with respect to PFS and OS. Results using a smaller network focusing on only those regimens that are relevant in Europe were consistent with the primary analysis.
CONCLUSIONS
These comparative effectiveness data may help inform treatment selection in TIE patients with NDMM.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Dexamethasone; Humans; Lenalidomide; Multiple Myeloma; Network Meta-Analysis; Treatment Outcome
PubMed: 35246820
DOI: 10.1007/s12325-022-02083-8 -
BMJ Open Aug 2019Adverse events (AEs) associated with short-term corticosteroid use for respiratory conditions in young children. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Adverse events (AEs) associated with short-term corticosteroid use for respiratory conditions in young children.
DESIGN
Systematic review of primary studies.
DATA SOURCES
Medline, Cochrane CENTRAL, Embase and regulatory agencies were searched September 2014; search was updated in 2017.
ELIGIBILITY CRITERIA
Children <6 years with acute respiratory condition, given inhaled (high-dose) or systemic corticosteroids up to 14 days.
DATA EXTRACTION AND SYNTHESIS
One reviewer extracted with another reviewer verifying data. Study selection and methodological quality (McHarm scale) involved duplicate independent reviews. We extracted AEs reported by study authors and used a categorisation model by organ systems. Meta-analyses used Peto ORs (pORs) and DerSimonian Laird inverse variance method utilising Mantel-Haenszel Q statistic, with 95% CI. Subgroup analyses were conducted for respiratory condition and dose.
RESULTS
Eighty-five studies (11 505 children) were included; 68 were randomised trials. Methodological quality was poor overall due to lack of assessment and inadequate reporting of AEs. Meta-analysis (six studies; n=1373) found fewer cases of vomiting comparing oral dexamethasone with prednisone (pOR 0.29, 95% CI 0.17 to 0.48; I=0%). The mean difference in change-from-baseline height after one year between inhaled corticosteroid and placebo was 0.10 cm (two studies, n=268; 95% CI -0.47 to 0.67). Results from five studies with heterogeneous interventions, comparators and measurements were not pooled; one study found a smaller mean change in height z-score with recurrent high-dose inhaled fluticasone over one year. No significant differences were found comparing systemic or inhaled corticosteroid with placebo, or between corticosteroids, for other AEs; CIs around estimates were often wide, due to small samples and few events.
CONCLUSIONS
Evidence suggests that short-term high-dose inhaled or systemic corticosteroids use is not associated with an increase in AEs across organ systems. Uncertainties remain, particularly for recurrent use and growth outcomes, due to low study quality, poor reporting and imprecision.
Topics: Acute Disease; Administration, Inhalation; Administration, Intravenous; Administration, Oral; Adrenal Cortex Hormones; Asthma; Bronchiolitis, Viral; Child, Preschool; Croup; Dexamethasone; Fluticasone; Glucocorticoids; Growth Disorders; Headache; Humans; Infant; Injections, Intramuscular; Pneumonia; Prednisone; Respiratory Sounds; Respiratory Tract Diseases; Respiratory Tract Infections; Tremor; Vomiting
PubMed: 31375615
DOI: 10.1136/bmjopen-2018-028511 -
The Cochrane Database of Systematic... Jul 2019Morphea (morphoea) is an immune-mediated disease in which excess synthesis and deposition of collagen in the skin and underlying connective tissues results in hardened...
BACKGROUND
Morphea (morphoea) is an immune-mediated disease in which excess synthesis and deposition of collagen in the skin and underlying connective tissues results in hardened cutaneous areas. Morphea has different clinical features according to the subtype and stage of evolution of the disease. There is currently no consensus on optimal interventions for morphea.
OBJECTIVES
To assess the effects of treatments for people with any form of morphea.
SEARCH METHODS
We searched the following databases up to July 2018: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, LILACS, and five trial registers. We checked the reference lists of included studies for further references to relevant randomised controlled trials.
SELECTION CRITERIA
Randomised controlled trials of topical, intralesional, or systemic treatments (isolated or combined) in anyone who has been clinically diagnosed by a medical practitioner with any form of morphea. Eligible controls were placebo, no intervention, any other treatment, or different doses or duration of a treatment.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. The primary outcomes were global improvement of disease activity or damage assessed by a medical practitioner or by participants, and adverse effects. Secondary outcomes were improvement of disease activity and improvement of disease damage. We used GRADE to assess the quality of the evidence for each outcome.
MAIN RESULTS
We included 14 trials, with a total of 429 randomised participants, aged between 3 and 76 years. There were juvenile and adult participants; over half were female, and the majority had circumscribed morphea, followed by linear scleroderma. The settings of the studies (where described) included a dermatologic centre, a national laboratory centre, paediatric rheumatology and dermatology centres, and a university hospital or medical centre.The studies evaluated heterogenous therapies for different types of morphea, covering a wide range of comparisons. We were unable to conduct any meta-analyses. Seven studies investigated topical medications, two evaluated intralesional medications, and five investigated systemic medications. The study duration ranged from seven weeks to 15 months from baseline.We present here results for our primary outcomes for our four key comparisons. All of these results are based on low-quality evidence.The included studies were at high risk of performance, detection, attrition, and reporting bias.Global improvement of disease activity or damage after treatment may be higher with oral methotrexate (15 mg/m², maximum 20 mg, once a week, for 12 months or until disease flare) plus oral prednisone (1 mg/kg a day, maximum of 50 mg, in a single morning dose, for three months, and one month with gradually decreased dose until discontinuation) than with placebo plus oral prednisone in children and adolescents with active morphea (linear scleroderma, generalised morphea or mixed morphea: linear and circumscribed) (risk ratio (RR) 2.31, 95% confidence interval (CI) 1.20 to 4.45; number needed to treat for an additional beneficial outcome (NNTB) 3; 1 randomised controlled trial (RCT); 70 participants, all juvenile). This outcome was measured 12 months from the start of treatment or until flare of the disease. Data were not available separately for each morphea type. There may be little or no difference in the number of participants experiencing at least one adverse event with oral methotrexate (26/46) or placebo (11/24) (RR 1.23, 95% CI 0.75 to 2.04; 1 RCT; 70 participants assessed during the 12-month follow-up). Adverse events related to methotrexate included alopecia, nausea, headache, fatigue and hepatotoxicity, whilst adverse events related to prednisone (given in both groups) included weight gain (more than 5% of body weight) and striae rubrae.One three-armed RCT compared the following treatments: medium-dose (50 J/cm²) UVA-1; low-dose (20 J/cm²) UVA-1; and narrowband UVB phototherapy. There may be little or no difference between treatments in global improvement of disease activity or damage, as assessed through the modified skin score (where high values represent a worse outcome): medium-dose UVA-1 phototherapy versus low-dose UVA-1 group: MD 1.60, 95% CI -1.70 to 4.90 (44 participants); narrowband UVB phototherapy versus medium-dose UVA-1 group: MD -1.70, 95% CI -5.27 to 1.87 (35 participants); and narrowband UVB versus low-dose UVA-1 group: MD -0.10, 95% CI -2.49 to 2.29 (45 participants). This RCT included children and adults with active morphea (circumscribed morphea, linear scleroderma (with trunk/limb variant and head variant), generalised morphea, or mixed morphea), who received phototherapy five times a week, for eight weeks. Outcomes were measured at eight weeks from the start of treatment.Safety data, measured throughout treatment, from the same RCT (62 participants) showed that treatment with UVA-1 phototherapy may cause mild tanning compared to narrowband UVB: narrowband UVB versus medium-dose UVA-1: RR 0.03, 95% CI 0.00 to 0.42; 35 participants; narrowband UVB versus low-dose UVA-1: RR 0.03, 95% CI 0.00 to 0.41; 45 participants. However, there may be no difference in the number of participants reporting mild tanning when comparing medium and low dose UVA-1 phototherapy (RR 1.00, 95% CI 0.91 to 1.10; 44 participants). Transient erythema was reported in three participants with narrowband UVB and no participants in the low- or medium-dose UVA-1 groups.
AUTHORS' CONCLUSIONS
Compared to placebo plus oral prednisone, oral methotrexate plus oral prednisone may improve disease activity or damage in juvenile active morphea (linear scleroderma, generalised morphea or mixed morphea: linear and circumscribed), but there may be a slightly increased chance of experiencing at least one adverse event.When medium-dose UVA-1 (50 J/cm²), low-dose UVA-1 (20 J/cm²), and narrowband UVB were compared against each other in treating children and adults with active morphea (circumscribed morphea, linear scleroderma, generalised morphea and mixed morphea), there may be little or no difference between these treatments on global improvement of disease activity or damage. UVA-1 phototherapy may cause more mild tanning than narrowband UVB, but there may be no difference between medium- and low-dose UVA-1 phototherapy. These results are based on low-quality evidence.Limitations of data and analyses include risk of bias and imprecision (small number of participants or events and wide confidence intervals). We encourage multicentre RCTs to increase sample size and evaluate, with validated tools, different treatment responses according to the subtypes of morphea and age groups.
Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Female; Humans; Male; Methotrexate; Middle Aged; Phototherapy; Prednisone; Randomized Controlled Trials as Topic; Scleroderma, Localized; Young Adult
PubMed: 31309547
DOI: 10.1002/14651858.CD005027.pub5 -
Clinical and Experimental Dental... Feb 2023Granulomatosis with polyangiitis is an unusual multisystemic inflammatory disease, with vasculitis of small- and medium-sized vessels, with a predilection for... (Review)
Review
OBJECTIVE
Granulomatosis with polyangiitis is an unusual multisystemic inflammatory disease, with vasculitis of small- and medium-sized vessels, with a predilection for upper lower airways and kidneys. The etiology remains unknown although it may originate from different stimuli, in genetically susceptible patients.
MATERIALS AND METHODS
A detailed database search was performed. The variables were demographics, localization, histopathological findings, antineutrophil cytoplasmic autoantibody, cytoplasmic (c-ANCA) tests, treatment, and follow-up.
RESULTS
Fifty-two cases were identified; the mean age was 49.6 years, with a range from 6 to 87 years. It was most frequently seen in females (57.7%). The most common race was white (59.6%). The most frequent location was in the maxillary gingiva (28.8%), followed by both the upper and lower gingiva (19.2%). The most common clinical presentation was "strawberry gingivitis" (61.5%). The main symptom was pain, in 50%. Regarding the c-ANCA test, it was positive in 71.2% of cases. The most common therapy was prednisone and cyclophosphamide, utilized in 51.9%. The average follow-up was 23.6 months, and 88.5% of patients were still alive at follow-up.
CONCLUSION
The diagnosis initially was difficult to establish, an early diagnosis and treatment are mandatory. If untreated the disease can be associated with morbidity and mortality. For the oral clinician, this disease needs to be addressed in the differential diagnosis of oral lesions.
Topics: Female; Humans; Child; Adolescent; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Granulomatosis with Polyangiitis; Antibodies, Antineutrophil Cytoplasmic; Cyclophosphamide
PubMed: 36600477
DOI: 10.1002/cre2.706 -
The Cochrane Database of Systematic... May 2022Giant cell arteritis (GCA) is the most common form of systemic vasculitis in people older than 50 years of age. It causes granulomatous inflammation of medium- to... (Review)
Review
BACKGROUND
Giant cell arteritis (GCA) is the most common form of systemic vasculitis in people older than 50 years of age. It causes granulomatous inflammation of medium- to large-sized vessels. Tocilizumab is a recombinant monoclonal antibody directed against interleukin-6 receptors (IL-6R).
OBJECTIVES
To assess the effectiveness and safety of tocilizumab, given alone or with corticosteroids, compared with therapy without tocilizumab for treatment of GCA.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2020, Issue 1); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Science Information database (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). There were no date or language restrictions in the electronic search for trials. We last searched the electronic databases on 3 January 2020.
SELECTION CRITERIA
We included only randomized controlled trials (RCTs) that compared tocilizumab of any dosage regimen (alone or with corticosteroids) with therapy without tocilizumab that had a minimum follow-up of six months. Participants were at least 50 years of age, with biopsy-proven GCA or by large-vessel vasculitis by angiography, and met the American College of Rheumatology 1990 guidelines for GCA.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodology.
MAIN RESULTS
Main results We included two RCTs in the review. The studies were conducted in the USA, Canada, and Europe and enrolled a total of 281 participants with GCA, of whom 74% were women. The mean age of participants was 70 years, with new-onset or relapsing GCA, and fulfilled the 1990 American College of Rheumatology criteria with no uncontrolled comorbidities. Both studies were funded by F. Hoffmann-La Roche AG, the manufacturer of tocilizumab. Findings One RCT (30 participants) compared tocilizumab administered every four weeks versus placebo. Point estimates at 12 months and beyond favored tocilizumab over placebo in terms of sustained remission (risk ratio (RR) 4.25, 95% confidence interval (CI) 1.21 to 14.88; moderate-certainty evidence). Point estimates suggest no evidence of a difference for all-cause mortality at 12 months or more (RR 0.17, 95% CI 0.01 to 3.94; moderate-certainty evidence). At 12 months, mean time to first relapse after induction of remission was 25 weeks in favor of participants receiving tocilizumab compared to placebo (mean difference (MD) 25, 95% CI 11.4 to 38.6; moderate-certainty evidence). The second RCT (250 participants) randomized participants into two intervention and two comparator groups to receive tocilizumab weekly (100 participants), bi-weekly (49 participants), weekly placebo + 26-week taper (50 participants), or weekly placebo + 52-week taper (51 participants). At 12 months, point estimates from this study on proportion of participants with sustained remission favored participants who received tocilizumab weekly versus placebo + 52-week taper (RR 3.17, 95% CI 1.71 to 5.89; 151 participants); tocilizumab weekly versus placebo + 26-week taper (RR 4.00, 95% CI 1.97 to 8.12; 150 participants); tocilizumab every other week versus placebo + 52-week taper (RR 3.01, 95% CI 1.57 to 5.75; 100 participants); tocilizumab every other week versus placebo + 26-week taper (RR 3.79, 95% CI 1.82 to 7.91; 99 participants) (moderate-certainty evidence). Point estimates on proportion of participants who did not need escape therapy (defined by the study as the inability to keep to the protocol-defined prednisone taper) favored participants who received tocilizumab weekly versus placebo + 52-week taper (RR 1.71, 95% CI 1.24 to 2.35; 151 participants); tocilizumab weekly versus placebo + 26-week taper (RR 2.96, 95% CI 1.83 to 4.78; 150 participants); tocilizumab every other week versus placebo + 52-week taper (RR 1.49, 95% CI 1.04 to 2.14; 100 participants) but not tocilizumab every other week versus placebo + 26-week taper (RR 0.65, 95% CI 0.27 to 1.54; 99 participants) (moderate-certainty evidence). This study did not report mean time to first relapse after induction of remission or all-cause mortality. Across comparison groups, the same study found no evidence of a difference in vision changes and inconsistent evidence with regard to quality of life. Evidence on quality of life as assessed by the physical (MD 8.17, 95% CI 4.44 to 11.90) and mental (MD 5.61, 95% CI 0.06 to 11.16) component score of the 36-Item Short Form Health Survey (SF-36) favored weekly tocilizumab versus placebo + 52-week taper but not bi-weekly tocillizumab versus placebo + 26-week taper (moderate-certainty evidence). Adverse events One RCT reported a lower percentage of participants who experienced serious adverse events when receiving tocilizumab every four weeks versus placebo. The second RCT reported no evidence of a difference among groups with regard to adverse events; however, fewer participants reported serious adverse events in the tocilizumab weekly and tocilizumab biweekly interventions compared with the placebo + 26-week taper and placebo + 52-week taper comparators. Investigators in both studies reported that infection was the most frequently reported adverse event.
AUTHORS' CONCLUSIONS
This review indicates that tocilizumab therapy may be beneficial in terms of proportion of participants with sustained remission, relapse-free survival, and the need for escape therapy. While the evidence was of moderate certainty, only two studies were included in the review, suggesting that further research is required to corroborate these findings. Future trials should address issues related to the required duration of therapy, patient-reported outcomes such as quality of life and economic outcomes, as well as the clinical outcomes evaluated in this review.
Topics: Adrenal Cortex Hormones; Aged; Antibodies, Monoclonal, Humanized; Female; Giant Cell Arteritis; Humans; Male; Recurrence
PubMed: 35560150
DOI: 10.1002/14651858.CD013484.pub3 -
The Cochrane Database of Systematic... Aug 2021Giant cell arteritis (GCA) is the most common form of systemic vasculitis in people older than 50 years of age. It causes granulomatous inflammation of medium- to... (Review)
Review
BACKGROUND
Giant cell arteritis (GCA) is the most common form of systemic vasculitis in people older than 50 years of age. It causes granulomatous inflammation of medium- to large-sized vessels. Tocilizumab is a recombinant monoclonal antibody directed against interleukin-6 receptors (IL-6R).
OBJECTIVES
To assess the effectiveness and safety of tocilizumab, given alone or with corticosteroids, compared with therapy without tocilizumab for treatment of GCA.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2020, Issue 1); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Science Information database (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). There were no date or language restrictions in the electronic search for trials. We last searched the electronic databases on 3 January 2020.
SELECTION CRITERIA
We included only randomized controlled trials (RCTs) that compared tocilizumab of any dosage regimen (alone or with corticosteroids) with therapy without tocilizumab that had a minimum follow-up of six months. Participants were at least 50 years of age, with biopsy-proven GCA or by large-vessel vasculitis by angiography, and met the American College of Rheumatology 1990 guidelines for GCA.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodology.
MAIN RESULTS
Main results We included two RCTs in the review. The studies were conducted in the USA, Canada, and Europe and enrolled a total of 281 participants with GCA, of whom 74% were women. The mean age of participants was 70 years, with new-onset or relapsing GCA, and fulfilled the 1990 American College of Rheumatology criteria with no uncontrolled comorbidities. Both studies were funded by F. Hoffmann-La Roche AG, the manufacturer of tocilizumab. Findings One RCT (30 participants) compared tocilizumab administered every four weeks versus placebo. Point estimates at 12 months and beyond favored tocilizumab over placebo in terms of sustained remission (risk ratio (RR) 4.25, 95% confidence interval (CI) 1.21 to 14.88; moderate-certainty evidence). Point estimates suggest no evidence of a difference for all-cause mortality at 12 months or more (RR 0.17, 95% CI 0.01 to 3.94; moderate-certainty evidence). At 12 months, mean time to first relapse after induction of remission was 25 weeks in favor of participants receiving tocilizumab compared to placebo (mean difference (MD) 25, 95% CI 11.4 to 38.6; moderate-certainty evidence). The second RCT (251 participants) randomized participants into two intervention and two comparator groups to receive tocilizumab weekly (100 participants), bi-weekly (49 participants), weekly placebo + 26-week taper (50 participants), or weekly placebo + 52-week taper (51 participants). At 12 months, point estimates from this study on proportion of participants with sustained remission favored participants who received tocilizumab weekly versus placebo + 52-week taper (RR 3.17, 95% CI 1.71 to 5.89; 151 participants); tocilizumab weekly versus placebo + 26-week taper (RR 4.00, 95% CI 1.97 to 8.12; 150 participants); tocilizumab every other week versus placebo + 52-week taper (RR 3.01, 95% CI 1.57 to 5.75; 100 participants); tocilizumab every other week versus placebo + 26-week taper (RR 3.79, 95% CI 1.82 to 7.91; 99 participants) (moderate-certainty evidence). Point estimates on proportion of participants who did not need escape therapy (defined by the study as the inability to keep to the protocol-defined prednisone taper) favored participants who received tocilizumab weekly versus placebo + 52-week taper (RR 1.71, 95% CI 1.24 to 2.35; 151 participants); tocilizumab weekly versus placebo + 26-week taper (RR 2.96, 95% CI 1.83 to 4.78; 150 participants); tocilizumab every other week versus placebo + 52-week taper (RR 1.49, 95% CI 1.04 to 2.14; 100 participants); tocilizumab every other week versus placebo + 26-week taper (RR 0.65, 95% CI 0.27 to 1.54; 99 participants) (moderate-certainty evidence). This study did not report mean time to first relapse after induction of remission or all-cause mortality. The same study found no evidence of a difference between groups with regard to vision changes and quality of life, except for the assessment of quality of life with the physical component score of the 36-Item Short Form Health Survey (SF-36), which favored weekly tocilizumab versus placebo + 52-week taper (MD 8.17, 95% CI 4.44 to 11.90; moderate-certainty evidence). Adverse events One RCT reported a lower percentage of participants who experienced serious adverse events when receiving tocilizumab every four weeks versus placebo. The second RCT reported no evidence of a difference among groups with regard to adverse events; however, fewer participants reported serious adverse events in the tocilizumab weekly and tocilizumab biweekly interventions compared with the placebo + 26-week taper and placebo + 52-week taper comparators. Investigators in both studies reported that infection was the most frequently reported adverse event.
AUTHORS' CONCLUSIONS
This review indicates that tocilizumab therapy may be beneficial in terms of proportion of participants with sustained remission, relapse-free survival, and the need for escape therapy. While the evidence was of moderate certainty, only two studies were included in the review, suggesting that further research is required to corroborate these findings. Future trials should address issues related to the required duration of therapy, patient-reported outcomes such as quality of life and economic outcomes, as well as the clinical outcomes evaluated in this review.
Topics: Aged; Antibodies, Monoclonal, Humanized; Canada; Female; Giant Cell Arteritis; Humans; Male
PubMed: 34420204
DOI: 10.1002/14651858.CD013484.pub2