Treatment response to cyclophosphamide, rituximab, and bortezomib in chronic immune-mediated sensorimotor neuropathies: a retrospective cohort study

Abstract

Background: Up to 20% of patients with chronic immune-mediated sensorimotor neuropathies (CIN) do not respond adequately to first-line therapies. However, studies on further treatment are scarce. Methods: We analyzed retrospectively 200 CIN patients regarding disease characteristics and response to therapy with cyclophosphamide (CYP), rituximab (RTX), and bortezomib (BTZ). Treatment response was defined as improvement or stabilization of inflammatory neuropathy cause and treatment overall disability score (INCAT-ODSS). Results: A total of 48 of 181 patients (26.5%) received therapy with CYP, RTX, or BTZ. The most frequently and first used therapy was CYP (69%). More than 40% of patients needed a second or third treatment. Overall, 71 treatments were applied in 48 patients. The combination of up to all three treatments enhanced the response-rate to 90%. Treatment within 24 months after initial diagnosis resulted in significantly higher response rate than late treatment (79% versus 50 %, p = 0.04, χ2-test, n = 46) and in lower disability in long-term follow up (INCAT-ODSS 3.8 versus 5.8, p = 0.02, t-test, n = 48). Patients with Lewis-Sumner syndrome ( n = 9) and autoantibody mediated neuropathies ( n = 13) had excellent response rates after treatment with RTX (90–100%). In contrast, typical chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) showed a response rate of 64% in CYP, 64% in RTX, and 75% in BTZ. Conclusion: Treatment with CYP, RTX, or BTZ was effective in this cohort of CIN refractory to first-line treatment. Our data increase evidence for an early use of these therapies. High efficacy of RTX in Lewis-Sumner syndrome in contrast to typical CIDP suggests a distinct pathophysiology.

Report of a fulminant anti‐pan‐neurofascin‐associated neuropathy responsive to rituximab and bortezomib

“…Comparable to previously described cases of anti-pan-NF-associated neuropathies, 6,10,11 our patient presented with a progressive tetraplegia, sensory impairment, cranial nerve involvement, autonomic dysregulation and respiratory insufficiency. Although RTX has been described to be effective in paranodopathies, 9,10,12,13 we decided to escalate immunotherapy, adding BTZ additionally to RTX, IVIG, corticosteroids and PE due to the severe disability and to even increasing antibody titers of antineurofascin-antibodies. to improve.…”

“…Therapeutic strategies are needed as symptoms may be lifethreatening and may not respond to standard first-line CIDP treatment. [6][7][8][9] 2 | CASE DESCRIPTION Around 6 weeks before the initial medical consultation, a 52-year-old male patient noticed fluctuating genital and facial numbness. Prior conditions were class III obesity (BMI >40 kg/m 2 ), chronic pain syndrome due to degenerative changes of the spine and relapsing deep vein thrombosis.…”

Corneal inflammatory cell infiltration predicts disease activity in chronic inflammatory demyelinating polyneuropathy

“…Our data implicate that patients with risk of clinical deterioration can be identified early by measuring CIC count. That is important because early therapy escalation in inflammatory neuropathies has been described as beneficial 4 , 5 . However, CCM does not allow therapeutic decisions based solely on the CIC count.…”

“…Corneal nerve fiber reduction was shown in several types of neuropathy including immune-mediated neuropathies 26 – 28 , however acute upcoming disease activity was not analyzed in these studies. Taken together, both information, acute cell infiltration and axonal damage, are important but different aspects of the disease 4 .…”

“…Up to 30% of all CIDP patients require a therapy escalation due to an aggressive disease course 1 . In such patients, early therapy adjustment appears to prevent clinical disability 1 – 4 . Therefore, early and reliable biomarkers are essential to detect patients at risk with active disease course 5 .…”