Introduction
Methods
Search strategy
Studies selection
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Problem/population: patients affected by PMR
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Intervention: GC treatment
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Comparison: control group was not required
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Outcome: GC persistence/withdrawal and annual flare rate at 1, 2, 3, 4, and 5 years since treatment initiation for meta-analysis; GC persistence/withdrawal and flare rate over the entire follow-up for qualitative analysis
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Study design: observational prospective and retrospective longitudinal studies
Data collection process
Statistical analysis
Results
Study selection
Long-term treatment with GCs in PMR
Author, year [ref] | Assessment time (yrs) | Patients (N) | Type of study | Recruitment period | Classification of PMR | PDN start dose(mg/day) |
---|---|---|---|---|---|---|
Aoki A, 2020 [15] | 2 | 64 | R | 2011–2020 | ACR/EULAR and Bird’s criteria | M 13.5 |
Mørk C, 2020 [16] | 1, 2 | 174, 173 | R/P | 2012–2017 | Physician’s diagn | Me 15 |
Marsman DE, 2020 [17] | 1, 2 | 441, 357 | R | 2008–2018 | Physician’s diagn | Me 15 |
Muller S, 2019 [18] | 1, 2 | 493, 437 | P | 2012–2014 | Physician’s diagn | M 15.6 |
van Sleen Y, 2019 [19] | 2 | 19 | P | 2010–2018 | Physician’s diagn | Me 15 |
Giollo A, 2019 [20] | 2 | 205 | P | na– > 2017 | ACR/EULAR | NA |
Albrecht K, 2018 [21] | 1, 2 | 526, 315 | P | 2007–2014 | Physician’s diagn | Me 7.5 |
Shbeeb I, 2018 [22] | 1, 2, 5 | 334, 302, 201 | R | 200–2014 | ACR/EULAR | M 16.9 |
Miceli MC, 2017 [23] | 1 | 66 | P | na | ACR/EULAR | 0.2 mg/kg/day |
Mackie SL, 2015 [24] | 1 | 21 | R | na | Bird’s | 15 per protocol |
Mazzantini M, 2012 [4] | 2 | 222 | R | na – > 2009 | Bird’s | M 15 |
Mackie SL, 2010 [25] | 5 | 164 | R | 1989–2000 | Bird’s | 29% > 15 mg/day |
Cimmino M, 2008 [26] | 5 | 57 | Obs.ext. of RCT | 1998–1999 | Chuang’s | NA |
Kremers H, 2007 [27] | 5 | 364 | R | 1970–1999 | Physician’s diagn | Me 15 |
Myklebust G, 2001 [28] | 1, 2 | 217, 217 | P | 1987–1994 | Bird’s criteria | Me 15 |
Weyand CM, 1999 [29] | 1 | 27 | P | 1993–1996 | Descriptive | 20 per protocol |
Ayoub WT, 1985 [30] | 1, 2 | 75, 75 | R | 1975–1982 | Descriptive | M 22.8 |
Rate of relapse in PMR
Author, year | Assessment times (yrs) | Patients (N) | Type of study | Recruitment period | classification Criteria | Criteria for relapse |
---|---|---|---|---|---|---|
Mørk C, 2020 [16] | 1 | 174 | R / P | 2012–2017 | Physician’s diagn | C, L |
Ayano M, 2020 [31] | 1 | 32 | R | 2011–2017 | Bird’s | C, L, T |
Do JG, 2018 [32] | 1 | 34 | R | 2009–2017 | ACR/EULAR | C, L |
Mackie SL, 2015 [24] | 1 | 21 | R | NA | Bird’s | NS |
Lee JH, 2013 [33] | 1 | 39 | R | NA | Bird’s | C, L |
Macchioni 2009 [34] | 1 | 57 | P | NA | Descriptive | C, L |
Weyand CM, 1999 [29] | 1 | 27 | P | 1993–1996 | Descriptive | NS |
Predictors of prolonged GC treatment and relapse
Author, year | Patients (N) | Type of Study | Recruitment period | Classification criteria | Potential predictors of long-term GC treatment |
---|---|---|---|---|---|
Hattori K, 2020 [35] | 50 | R | 2010–2017 | Bird’s ACR/EULAR | Normalization of CRP at 1 month associated with higher likelihood of achievement of GC-free remission (OR = 5.83). No association was recorded with age and sex |
Aoki A, 2020 [15] | 93 | R | 2011–2020 | Bird’s ACR/EULAR | Relapse till 6 months associated with long-term GC therapy (OR 6.40). No association was demonstrated with age, sex, APR, GC starting dose |
Marsman DE, 2020 [17] | 454 | R | 2008–2018 | Physician’s diagn | Normal APR had shorter median time to GC-free remission (552 vs. 693 days). However, when the GC-retention rate at 1 and 2 years were evaluated, no significant differences were identified. Analysis focused on APR; thus, other candidate predictors were not assessed |
Giollo A, 2019 [20] | 385 | R | < 2017 | ACR/EULAR | Older age (adjHR, 1.02), peripheral involvement (adjHR 1.38), higher CRP (adjHR 1.29), higher initial dosage of GC (adjHR 0.96), higher hemoglobin (adjHR 0.86), osteoporosis (adjHR0.75), and the use of amino bisphosphonates (adjHR0.65) associated with persistence in GC therapy. A trend to significant association was recorded with relapses. No association with sex and MTX or other DMARDs was recorded |
Albrecht K, 2018 [21] | 172 | P | 2007–2014 | Physician's diagn | Baseline MTX (OR 2.03) GCs > 10 mg/day (OR 1.65), higher disease activity (OR 1.12) (median 0.6 years DD), and female sex (OR 1.63 [1.09–2.43]) were predictive for GC therapy at ≥ 3 years. No association was found with age and APR |
Shbeeb I, 2018 [22] | 359 | R | 200–2014 | ACR/EULAR | Initial dose of GC was not associated with time to permanent discontinuation (HR 1.06 per 5 mg/day increase, 95% CI 0.96–1.18). Other possible predictors were not assessed |
Miceli MC, 2017 [23] | 66 | P | na | ACR/EULAR | N of GC-free patients at 12 months was comparable among patients with or without musculoskeletal ultrasonography (MSUS) inflammatory findings at the baseline [14 (30.4%) in MSUS-positive vs 6 (30.0%) in MSUS-negative |
Mackie SL, 2010 [25] | 22 | R | 1989–2000 | Bird’s | A higher plasma viscosity increases the risk of prolonged steroid therapy and late GCA. Starting patients on > 15 mg prednisolone is associated with a prolonged steroid duration. Age and sex did not associate with risk of prolonged GC duration |
Cimmino MA, 2008 [26] | 57 | Obs. Ext. of RCT | 1998–1999 | Chuang’s | No GC-sparing effect of MTX was demonstrated. Other DMARDs were not assessed. Age, sex and APR did not associate with GC treatment duration |
Myklebust G, 2001 [28] | 217 | P | 1987–1994 | Bird’s | Higher mean maintenance GC dose in 1st yr (6.1 vs. 4.8 mg/day of PDN), higher mean pretreatment ESR (73 vs. 60 mm/h) lower hemoglobin (12.3 vs. 12.9 g/dL). No significant association with initial GC dosage and APR |
Weyand CM, 1999 [29] | 27 | P | 1993–1996, > 1 yr | Physician’s diagn | ESR and non-responsiveness of interleukin 6 to steroid therapy are helpful in dividing patients into subsets with different treatment requirements |
Author, year | Patients (N) | Type of study | Recruitment period | Classification criteria | Relapse criteria | Relapse rate | Potential predictors of relapses |
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Lee JH, 2013 [33] | 39 | R | na | Bird's | C, L | 15 (38%) | Initial CRP > 2.5 mg/dl (OR 6.3) and the use of hydroxychloroquine (OR 6.798). Female gender (OR 10.683, p = 0.052). MTX and other DMARDs did not associated with occurrence of relapse |
Macchioni P, 2009 [34] | 57 | P | na | na | C, L, T | 22 (39%) | Positive PD signal at diagnosis (63.6 vs 15.4%) |
de la Torre ML, 2020 [36] | 86 | P | 2017 | C.L | 40 (47%) 15 (17%) | MTX in PMR patients who already had a relapse reduced the number of future relapses and decreased the time to achieve remission | |
Fukui S, 2016 [37] | 115 | P | 2004–2013 | ACR/EULAR | C, L, T | 29 (23%) | Female gender (OR 2.73) and creatinine > 50 μmol/L (OR, 2.48) associated with occurrence of relapses. No association was reported between occurrence of relapse and age, APR, GC initial dose, speed of GC tapering and peripheral arthritis |
Kimura M, 2012 [38] | 123 | R | 2000–2009 | Hunder’s | C, L | 29 (23%); 7 (5.7%) | No significant difference with RS3PE |
Mackie SL, 2010 [24] | 169 | R | 1989–2000 | Bird’s | C, T | 83 (49.1%) | No association was recorded between occurrence of relapses and age, sex, APR and GC initial does |
Boiardi L, 2006 [39] | 112 | P | 1993–1997 | ns | C, L | 49 (43.7%) | Persistently elevated IL- 6 levels, but not the CC genotype |
Cimmino MA, 2008 [26] | 57 | Obs. Ext. of RCT | 1998–1999 | Chuang’s | C. L.T | 20 (35%) | Flare- ups of PMR were seen in 8/26 (30.8%) MTX-treated patients in comparison with 12/27 (44.4%) controls |
Salvarani C, 2005 [40] | 94 | P | 1994–1997 | Descriptive | C, L, T | 47 (50.0%) | Persistently elevated levels of CRP (RR ranging between 2 and 5) and persistently elevated levels of IL-6 (RR 4–13) associated with occurrence of relapses. Age, sex and GC initial dose and peripheral arthritis did not predict relapses |
Kremers HM, 2005 [41] | 284 | R | 1970–1999 | Descriptive | C, T | 55% | Higher ESR (HR 1.14); higher initial GCs dose (HR 1.07); fast tapering of GCs (HR 4.27), medium CS tapering (HR 2.19). Age, sex and peripheral arthritis did not associate with relapses |
Martínez-Taboda VM, 2004 [42] | 54 | R | na | Descriptive | C, T | 18 (33.3%) | Increased expression of the HLA-DRB1*09 allele (5.6% vs 0%) |
Gonzalez-Gay MA, 2002 [43] | 86 | R | na | Descriptive | C, L*, T | 18 (20.9%) 3 (3.5%) | No differences in CRH-A or B alleles and genotypes |
Amoli MM, 2002 [44] | 72 | R | na | Descriptive | C, T | 18 (22%) | HLA-DRB1*0401 and the ICAM-1 codon 241 GG homozygosity |
Boiardi L, 2000 [45] | 92 | P | 1992–1996 | Descriptive | C, L, T | 40 (44%) | IL-1A (+ 4845), IL-B (-511), IL-B (+ 3954), IL-1RN Intron 2 VNTR and TNFA (-308) no associated with the disease severity |
Salvarani C, 2000 [46] | 88 | P | 1992–1996 | Descriptive | C, L, T | 37 (42%) | No association with CCR5∆32 |