Intrathecal IgG Synthesis: A Resistant and Valuable Target for Future Multiple Sclerosis Treatments

Table 1

Posttreatment change in intrathecal synthesis.

References	Drugs		Time to follow up LP	IgG index^1	OCB+^2	IT synthesis^3
[79]	IV methylpred.; (1 g/d/3 d)	7	5 days	IgG 1.7 → 1.1^**	7/9 → 5/8	Tourt. 26 → 13 mg/L^*
[78]	IV methylpred.; (1 g/d/10 d)	101	10 days	IgG 1.05 → 0.98^**; IgM 0.13 → 0.12	92% → 82%^**	IgGLoc 31 → 11 mg/L^**; (85% → 70%^**); IgMLoc 1.0 → 0.4 mg/L^**; (32% → 27%^**)
[94]	CCNU	4	10 weeks	N/A	N/A	Tourt.; Baseline: 59.5 ± 34.8 mg/d; Weeks 1-2: −6.3 ± 5.3 mg/d; Weeks 3–5: −6.8 ± 8.1 mg/d; Weeks 6–10: −11.8 ± 7.5 mg/d^*
[134]	Natalizumab	6	10 months	(2/4 → 1/6)	(6/6 → 2/6)	N/A
[136]	Natalizumab	24	24 months	0.88 → 0.64^**; 67% → 33%^**	92% → 42%^**	IgGLoc  0.52 → 0.0 mg/L
[137]	Natalizumab	24	60 weeks	Unchanged	(17/17 → 16/17)	N/A
[138]	Natalizumab	59	30 months	Decreased; (−0.18)^*	N/A → 94%	IgGLoc  −12.1 mg/L^**; IgMLoc  −0.2 mg/L^**
[135]	Natalizumab	73	30 months	N/A	100% → 84%^**	80% → 55%^**
[76]	IV rituximab	13	24 weeks	Unchanged	Unchanged	Unchanged
[152]	IT rituximab 10 mg/m/2 months	1	2 months	IgG 4.02 → 3.86	Unchanged	N/A

Unless explicitly mentioned, no change is statistically significant. ¹Mean IgG index is provided when available: elsewhere abnormal IgG indexes (>0.7) are provided as number or per cent of patients. ²OCB (IEF) are described as number or per cent of patients. Owing to subjectivity in counting, changes in mean OCB number are not taken into account. ³IT synthesis is assessed when > . Proportion of abnormal synthesis, IgG_Loc, or mean changes of IgG_Loc are reported. N/A: not assessed. Follow-up results without statistically significant changes are categorized as “unchanged.” Since our objective was an eventual normalization of intrathecal synthesis, we did not report synthesis fluctuations when they were not associated with at least normalization of results in some patients. For example, in [76], IgG synthesis rate decreased by 30% in 6 while increasing by 30% in 3 patients, but none achieved normal synthesis. ^*; ^**.