Table 1.
Cases of confirmed PML in patients with RA
| Characteristic | Case 1 (Fleischmann 2009) | Case 2 (Clifford et al. 2011) | Case 3 (Clifford et al. 2011) | Case 4 (Clifford et al. 2011) | Case 5 (Clifford et al. 2011) | Case 6 | Case 7 | Case 8 | Case 9 |
|---|---|---|---|---|---|---|---|---|---|
| Age, years | 50 | 72 | 72 | 62 | 71 | 56 | 58 | 60 | 83 |
| Sex | F | F | F | F | F | F | M | F | F |
| Country | USA | USA | USA | Australia | Sweden | USA | Netherlands | USA | Germany |
| Date PML confirmed | May 2008 | Nov. 2008 | Sept. 2009 | Oct. 2009 | Nov. 2009 | March 2010 | Not specified | Aug. 2012 | Nov. 2014 |
| Duration of RA, years | 14 | 30 | 3 | 20 | 3 | 6 | 11 | 5 | 7 |
| Relevant medical history | Radiation, Sjögren syndrome with lymphopenia, undetectable complement and CD4, lymphadenopathy | Sjögren syndrome | Sjögren syndrome | Leukopenia | Lymphopenia at baseline, secondary Sjögren syndrome, radiation | None reported | SLE, ANA and anti-DNA antibodies positive, opportunistic infections | SLE | None reported |
| History of malignancy | Yes | No | No | No | Yes | No | No | No | No |
| Prior nonbiologicsa, b | MTX, steroids, HCQ, etodolac | MTX, steroids | Steroids, leflunomide, HCQ | Leflunomide, sulfasalazine, gold, HCQ, steroids | MTX, steroids | Leflunomide MTX | MTX, steroids, sulfasalazine, HCQ | Azathioprine, MTX, CYC, HCQ | MTX, Steroids |
| Prior biologicsa | Infliximab | Adalimumab, etanercept | None | Adalimumab, etanercept, anakinra | None | Adalimumab, etanercept | Etanercept, infliximab | None | Denosumab |
| Concomitant druga, b | MTX, steroids | MTX, steroids | Steroids, leflunomide, HCQ | MTX | HCQ, steroids | MTX, steroids, leflunomide | MTX, steroids | Steroids, MMF | MTX, steroids |
| Rituximab treatment, no. of coursesbc | 4 | 5 | 1 | ≈ 4 | 2 | 3 | 4 | 9 | unspecified |
| Latency distribution (time from first rituximab infusion to PML diagnosis) | 5 years from first dose and 18 months from last dose | ≈ 26 months after first dose and ≈ 2 months from last dose | ≈ 7 months | ≈ 18 months from first dose and ≈ 3 months from last dose | ≈ 15 months from first dose. Not specified relative to last dose | ≈ 23 months from first dose and ≈ 6 months from last dose | ≈ 28 months from first dose and ≈ 2 months from last dose | ≈ 56 months from first rituximab dose and ≈ 6 months from last rituximab dose | ≈ 57 months from first rituximab dose and ≈ 8 months from last rituximab dose |
| PML treatment | None reported | Mefloquine | Mefloquine | Mirtazapine and mefloquine | Mirtazapine and mefloquine | Plasmapheresis and mefloquine | Mirtazapine and nitrofurantoin | None reported | None reported |
| Outcome | Fatal | Fatal | Fatal | Recovering | Recovering | Unknown | Fatal | Fatal | Fatal |
ANA, antinuclear antibody; CYC, cyclophosphamide; F, female; HCQ, hydroxychloroquine; M, male; MMF, mycophenolate mofetil; MTX, methotrexate; PML, progressive multifocal leukoencephalopathy; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus
aMMF is a class 2 agent and adalimumab, azathioprine, CYC, etanercept, infliximab, and MTX are class 3 agents, with respect to known or possible risk for PML
bMMF had a PML risk signal, and azathioprine and CYC had possible PML risk signals in a disproportionality analysis of spontaneous PML reports (Chahin and Berger 2015)
cPer the rituximab label recommendations for RA, one treatment course consists of 2 × 1000 mg intravenous infusions separated by 2 weeks, with treatment courses repeated every 24 weeks based on clinical evaluation, but no sooner than every 16 weeks